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Balance caution with necessity when prescribing dermatology drugs in pregnancy
NEW YORK – Disease exacerbations during pregnancy can be more dangerous for the fetus than some of the medications used to treat them..
No one wants to take unnecessary drugs during pregnancy, Dr. Jenny Murase said at the American Academy of Dermatology summer meeting. But concern about medication safety should never override the need to treat new-onset disease or control existing disorders.
“Often, patients are so worried about the effects of medicines on the baby that they don’t think about the effects of the disease. This is a thing we need to address with each patient. What would happen to you, and your baby, if this disease is not treated?” said Dr. Murase of the Palo Alto Foundation Medical Group, San Francisco.
Primary herpes simplex infections are an excellent example of this dilemma, she said. “Primary HSV has up to a 50% transmission rate to the fetus. In utero infections are associated with microcephaly, hydrocephalus, and chorioretinitis. About a third of neonates have central nervous system disease, and a quarter are born with disseminated disease,” and the neonatal mortality rate is nearly 70%.
“On the other hand, acyclovir is very, very safe,” based on data on thousands of patients, Dr. Murase said. Famciclovir and valacyclovir are also likely safe but data on those drugs are more limited, she added.
Sometimes, ideas about a drug’s safety during pregnancy are based on old or confusing studies. The worries about the teratogenicity of systemic steroids, for example, stem from a 1951 report that cortisone caused orofacial cleft in prenatally exposed mice.
“Since then, no prospective studies have found any evidence of congenital malformations associated with systemic steroids,” Dr. Murase said. However, “epidemiologic studies have suggested a threefold increase, which, interestingly, is in line with the mouse findings.”
The drugs do, however, have an important place in the armamentarium; they should be used judiciously and as part of a careful risk-benefit analysis. Both betamethasone and dexamethasone pass the placental barrier well; prednisone is not as transferable.
Dr. Murase provided a list of some medications commonly employed in dermatologic practice, with considerations for their use during pregnancy.
• Topical steroids. A 2013 study found that pregnancy-long exposure to more than 300 g of a potent or superpotent topical corticosteroid did not increase risk of orofacial cleft in the newborn, but did increase risk of low birth weight. “So if you are giving more than five tubes of 60 g, there is a potential for low birth weight – although this could also be related to the actual severity of the disease. Still, you should discuss this risk with your patient.”
• Antihistamines. These should be avoided in the last month of pregnancy as they can stimulate uterine contractions, especially if they are given intravenously or in very high doses. There have been reports of a doubling of retinopathy in premature infants (22% vs. 11%) associated with antihistamines used within 2 weeks of delivery. Some infants can have withdrawal symptoms, including seizure, if the mother has been taking high doses of the drugs.
• Antibiotics. The first-line antibiotics are penicillin, cephalosporins, and dicloxacillin; all are safe. Of the macrolides, erythromycin is preferred. However, the estolate form of the drug has been associated with reversible abnormalities in liver enzymes; the base and ethylsuccinate forms don’t have this risk. Rifampin may be used, but vitamin K should be given with it. Sulfonamides are a second-line choice up until the third trimester. They shouldn’t be used after that, as they can cause anemia, hyperbilirubinemia, and kernicterus. Tetracycline can be used up to 14 weeks’ gestation but not after that, because of the risks of bone growth inhibition and tooth discoloration in the infant, and maternal hepatitis.
• Antifungals. Topical antifungals are not too concerning. Nystatin is safe, but not as effective as the later-generation medications. Clotrimazole is the first choice, followed by miconazole and ketoconazole. Data are limited, but topical terbinafine, naftifine, and ciclopirox are also probably safe, she said.
Systemic antifungals are a different matter. None of the imidazole derivatives are advised during pregnancy, as they have been associated with craniosynostosis, congenital heart defects, and skeletal anomalies. If they are used, a diagnostic ultrasound at 20 weeks is advisable.
• Light. Light therapy is generally considered safe, although there is some evidence that narrow-band ultraviolet can deplete folic acid levels. Despite that, there are no reports of neural tube or orofacial defects associated with light therapy. Nevertheless, make sure patients are supplementing with folic acid if they receive light therapy.
Light therapy should never be combined with oxsoralen in pregnant women; the drug is a known mutagen. Data on cyclosporine are more limited, but it’s a category C drug in pregnancy, so it’s best to avoid it.
• Biologics. Etanercept, adalimumab, infliximab, and alefacept are all category B drugs in pregnancy. There are some hints that they, as well as tumor necrosis factor (TNF)-inhibitors, may be associated with some fetal anomalies in the VACTERL association cluster (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities). A confirmation of the syndrome requires three signs to be present. Only two infants born to mothers taking a biologic have had three qualifying signs.
However, pregnancy outcome reports for the drugs have recorded malformations. Among the adalimumab cohorts totaling 256 pregnancies, there were 14 fetal anomalies (5.5%); of these, nine were VACTERL-related. In the etanercept cohorts totaling 204 pregnancies, there were 13 anomalies (6.4%); of these, six were VACTERL-related. In the infliximab cohorts totaling 112 pregnancies, there was only one anomaly, which was in the VACTERL cluster. Among the 407 pregnancies in the TNF-inhibitors, there were three anomalies, none of which were related to VACTERL.
Dr. Murase had no financial disclosures relevant to her talk.
The current system of using letter categories to denote risk of prescription drugs during pregnancy and breastfeeding is being replaced by the Food and Drug Administration, with the addition of subsections in drug labeling.
On Twitter @Alz_Gal
NEW YORK – Disease exacerbations during pregnancy can be more dangerous for the fetus than some of the medications used to treat them..
No one wants to take unnecessary drugs during pregnancy, Dr. Jenny Murase said at the American Academy of Dermatology summer meeting. But concern about medication safety should never override the need to treat new-onset disease or control existing disorders.
“Often, patients are so worried about the effects of medicines on the baby that they don’t think about the effects of the disease. This is a thing we need to address with each patient. What would happen to you, and your baby, if this disease is not treated?” said Dr. Murase of the Palo Alto Foundation Medical Group, San Francisco.
Primary herpes simplex infections are an excellent example of this dilemma, she said. “Primary HSV has up to a 50% transmission rate to the fetus. In utero infections are associated with microcephaly, hydrocephalus, and chorioretinitis. About a third of neonates have central nervous system disease, and a quarter are born with disseminated disease,” and the neonatal mortality rate is nearly 70%.
“On the other hand, acyclovir is very, very safe,” based on data on thousands of patients, Dr. Murase said. Famciclovir and valacyclovir are also likely safe but data on those drugs are more limited, she added.
Sometimes, ideas about a drug’s safety during pregnancy are based on old or confusing studies. The worries about the teratogenicity of systemic steroids, for example, stem from a 1951 report that cortisone caused orofacial cleft in prenatally exposed mice.
“Since then, no prospective studies have found any evidence of congenital malformations associated with systemic steroids,” Dr. Murase said. However, “epidemiologic studies have suggested a threefold increase, which, interestingly, is in line with the mouse findings.”
The drugs do, however, have an important place in the armamentarium; they should be used judiciously and as part of a careful risk-benefit analysis. Both betamethasone and dexamethasone pass the placental barrier well; prednisone is not as transferable.
Dr. Murase provided a list of some medications commonly employed in dermatologic practice, with considerations for their use during pregnancy.
• Topical steroids. A 2013 study found that pregnancy-long exposure to more than 300 g of a potent or superpotent topical corticosteroid did not increase risk of orofacial cleft in the newborn, but did increase risk of low birth weight. “So if you are giving more than five tubes of 60 g, there is a potential for low birth weight – although this could also be related to the actual severity of the disease. Still, you should discuss this risk with your patient.”
• Antihistamines. These should be avoided in the last month of pregnancy as they can stimulate uterine contractions, especially if they are given intravenously or in very high doses. There have been reports of a doubling of retinopathy in premature infants (22% vs. 11%) associated with antihistamines used within 2 weeks of delivery. Some infants can have withdrawal symptoms, including seizure, if the mother has been taking high doses of the drugs.
• Antibiotics. The first-line antibiotics are penicillin, cephalosporins, and dicloxacillin; all are safe. Of the macrolides, erythromycin is preferred. However, the estolate form of the drug has been associated with reversible abnormalities in liver enzymes; the base and ethylsuccinate forms don’t have this risk. Rifampin may be used, but vitamin K should be given with it. Sulfonamides are a second-line choice up until the third trimester. They shouldn’t be used after that, as they can cause anemia, hyperbilirubinemia, and kernicterus. Tetracycline can be used up to 14 weeks’ gestation but not after that, because of the risks of bone growth inhibition and tooth discoloration in the infant, and maternal hepatitis.
• Antifungals. Topical antifungals are not too concerning. Nystatin is safe, but not as effective as the later-generation medications. Clotrimazole is the first choice, followed by miconazole and ketoconazole. Data are limited, but topical terbinafine, naftifine, and ciclopirox are also probably safe, she said.
Systemic antifungals are a different matter. None of the imidazole derivatives are advised during pregnancy, as they have been associated with craniosynostosis, congenital heart defects, and skeletal anomalies. If they are used, a diagnostic ultrasound at 20 weeks is advisable.
• Light. Light therapy is generally considered safe, although there is some evidence that narrow-band ultraviolet can deplete folic acid levels. Despite that, there are no reports of neural tube or orofacial defects associated with light therapy. Nevertheless, make sure patients are supplementing with folic acid if they receive light therapy.
Light therapy should never be combined with oxsoralen in pregnant women; the drug is a known mutagen. Data on cyclosporine are more limited, but it’s a category C drug in pregnancy, so it’s best to avoid it.
• Biologics. Etanercept, adalimumab, infliximab, and alefacept are all category B drugs in pregnancy. There are some hints that they, as well as tumor necrosis factor (TNF)-inhibitors, may be associated with some fetal anomalies in the VACTERL association cluster (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities). A confirmation of the syndrome requires three signs to be present. Only two infants born to mothers taking a biologic have had three qualifying signs.
However, pregnancy outcome reports for the drugs have recorded malformations. Among the adalimumab cohorts totaling 256 pregnancies, there were 14 fetal anomalies (5.5%); of these, nine were VACTERL-related. In the etanercept cohorts totaling 204 pregnancies, there were 13 anomalies (6.4%); of these, six were VACTERL-related. In the infliximab cohorts totaling 112 pregnancies, there was only one anomaly, which was in the VACTERL cluster. Among the 407 pregnancies in the TNF-inhibitors, there were three anomalies, none of which were related to VACTERL.
Dr. Murase had no financial disclosures relevant to her talk.
The current system of using letter categories to denote risk of prescription drugs during pregnancy and breastfeeding is being replaced by the Food and Drug Administration, with the addition of subsections in drug labeling.
On Twitter @Alz_Gal
NEW YORK – Disease exacerbations during pregnancy can be more dangerous for the fetus than some of the medications used to treat them..
No one wants to take unnecessary drugs during pregnancy, Dr. Jenny Murase said at the American Academy of Dermatology summer meeting. But concern about medication safety should never override the need to treat new-onset disease or control existing disorders.
“Often, patients are so worried about the effects of medicines on the baby that they don’t think about the effects of the disease. This is a thing we need to address with each patient. What would happen to you, and your baby, if this disease is not treated?” said Dr. Murase of the Palo Alto Foundation Medical Group, San Francisco.
Primary herpes simplex infections are an excellent example of this dilemma, she said. “Primary HSV has up to a 50% transmission rate to the fetus. In utero infections are associated with microcephaly, hydrocephalus, and chorioretinitis. About a third of neonates have central nervous system disease, and a quarter are born with disseminated disease,” and the neonatal mortality rate is nearly 70%.
“On the other hand, acyclovir is very, very safe,” based on data on thousands of patients, Dr. Murase said. Famciclovir and valacyclovir are also likely safe but data on those drugs are more limited, she added.
Sometimes, ideas about a drug’s safety during pregnancy are based on old or confusing studies. The worries about the teratogenicity of systemic steroids, for example, stem from a 1951 report that cortisone caused orofacial cleft in prenatally exposed mice.
“Since then, no prospective studies have found any evidence of congenital malformations associated with systemic steroids,” Dr. Murase said. However, “epidemiologic studies have suggested a threefold increase, which, interestingly, is in line with the mouse findings.”
The drugs do, however, have an important place in the armamentarium; they should be used judiciously and as part of a careful risk-benefit analysis. Both betamethasone and dexamethasone pass the placental barrier well; prednisone is not as transferable.
Dr. Murase provided a list of some medications commonly employed in dermatologic practice, with considerations for their use during pregnancy.
• Topical steroids. A 2013 study found that pregnancy-long exposure to more than 300 g of a potent or superpotent topical corticosteroid did not increase risk of orofacial cleft in the newborn, but did increase risk of low birth weight. “So if you are giving more than five tubes of 60 g, there is a potential for low birth weight – although this could also be related to the actual severity of the disease. Still, you should discuss this risk with your patient.”
• Antihistamines. These should be avoided in the last month of pregnancy as they can stimulate uterine contractions, especially if they are given intravenously or in very high doses. There have been reports of a doubling of retinopathy in premature infants (22% vs. 11%) associated with antihistamines used within 2 weeks of delivery. Some infants can have withdrawal symptoms, including seizure, if the mother has been taking high doses of the drugs.
• Antibiotics. The first-line antibiotics are penicillin, cephalosporins, and dicloxacillin; all are safe. Of the macrolides, erythromycin is preferred. However, the estolate form of the drug has been associated with reversible abnormalities in liver enzymes; the base and ethylsuccinate forms don’t have this risk. Rifampin may be used, but vitamin K should be given with it. Sulfonamides are a second-line choice up until the third trimester. They shouldn’t be used after that, as they can cause anemia, hyperbilirubinemia, and kernicterus. Tetracycline can be used up to 14 weeks’ gestation but not after that, because of the risks of bone growth inhibition and tooth discoloration in the infant, and maternal hepatitis.
• Antifungals. Topical antifungals are not too concerning. Nystatin is safe, but not as effective as the later-generation medications. Clotrimazole is the first choice, followed by miconazole and ketoconazole. Data are limited, but topical terbinafine, naftifine, and ciclopirox are also probably safe, she said.
Systemic antifungals are a different matter. None of the imidazole derivatives are advised during pregnancy, as they have been associated with craniosynostosis, congenital heart defects, and skeletal anomalies. If they are used, a diagnostic ultrasound at 20 weeks is advisable.
• Light. Light therapy is generally considered safe, although there is some evidence that narrow-band ultraviolet can deplete folic acid levels. Despite that, there are no reports of neural tube or orofacial defects associated with light therapy. Nevertheless, make sure patients are supplementing with folic acid if they receive light therapy.
Light therapy should never be combined with oxsoralen in pregnant women; the drug is a known mutagen. Data on cyclosporine are more limited, but it’s a category C drug in pregnancy, so it’s best to avoid it.
• Biologics. Etanercept, adalimumab, infliximab, and alefacept are all category B drugs in pregnancy. There are some hints that they, as well as tumor necrosis factor (TNF)-inhibitors, may be associated with some fetal anomalies in the VACTERL association cluster (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities). A confirmation of the syndrome requires three signs to be present. Only two infants born to mothers taking a biologic have had three qualifying signs.
However, pregnancy outcome reports for the drugs have recorded malformations. Among the adalimumab cohorts totaling 256 pregnancies, there were 14 fetal anomalies (5.5%); of these, nine were VACTERL-related. In the etanercept cohorts totaling 204 pregnancies, there were 13 anomalies (6.4%); of these, six were VACTERL-related. In the infliximab cohorts totaling 112 pregnancies, there was only one anomaly, which was in the VACTERL cluster. Among the 407 pregnancies in the TNF-inhibitors, there were three anomalies, none of which were related to VACTERL.
Dr. Murase had no financial disclosures relevant to her talk.
The current system of using letter categories to denote risk of prescription drugs during pregnancy and breastfeeding is being replaced by the Food and Drug Administration, with the addition of subsections in drug labeling.
On Twitter @Alz_Gal
EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2015
Turn down the androgens to treat female pattern hair loss
NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.
The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.
The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.
“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”
Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.
The initial challenge is simply what to label it at the first visit.
“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”
The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.
Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.
Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.
Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.
One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.
Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.
Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”
Dr. Torgerson had no financial conflicts with regard to her presentation.
On Twitter @Alz_Gal
NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.
The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.
The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.
“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”
Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.
The initial challenge is simply what to label it at the first visit.
“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”
The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.
Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.
Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.
Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.
One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.
Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.
Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”
Dr. Torgerson had no financial conflicts with regard to her presentation.
On Twitter @Alz_Gal
NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.
The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.
The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.
“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”
Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.
The initial challenge is simply what to label it at the first visit.
“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”
The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.
Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.
Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.
Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.
One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.
Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.
Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”
Dr. Torgerson had no financial conflicts with regard to her presentation.
On Twitter @Alz_Gal
EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2015
Nipple Raynaud’s can freeze out breastfeeding desire
NEW YORK – The “perfect storm” of pregnancy and lactation can throw breastfeeding moms into a painful deep freeze.
Almost 25% of women with lactation pain may actually be experiencing symptoms of Raynaud’s, Dr. Honor Fullerton Stone said at the American Academy of Dermatology summer meeting.
“Breastfeeding mothers are in a perfect storm,” of physical developments that predispose them to this vasoconstrictive phenomenon, said Dr. Fullerton Stone, who practices dermatology in Menlo Park, Ca. “Estrogen increases the alpha-adrenergic receptors on smooth muscle. Nerve irritation from constant breastfeeding upregulates those receptors. And emotional stress – crying baby, anyone? – increases epinephrine, which contributes further to vasoconstriction.”
She conducted a review of 88 of her own patients with nursing-related breast pain. Of these, about a quarter ended up with a diagnosis of nipple vasoconstriction. None of the women had a history of Raynaud’s disease.
Pain during a nursing session is the presenting complaint, but breastfeeding pain is incredibly nonspecific as a symptom. It’s the quality of the pain, Dr Stone said, that should ring a bell.
“There’s let-down pain, which occurs at latch and then comes on again later, with refill. There’s pain from candidiasis, which is dramatic at latch, like a radiating heat, but goes away rapidly after a few days of antifungals,” she noted. But with Raynaud’s, “the pain is persistent. It’s throbbing, which makes sense since it’s vascular. And it’s constant,” lasting through every nursing session, which she said is the kind of experience that makes mothers stop breastfeeding.
Since pain is such a pervasive symptom in breastfeeding complaints, women with vasoconstriction of the nipple are often misdiagnosed. They can go for months trying to improve latch technique or receiving antifungal therapy with no improvement, she said.
Dr. Stone considers a diagnosis of Raynaud’s if two of the following criteria are met:
• Color change of nipple, cold sensitivity, or color change of acral surfaces with cold exposure.
• Chronic deep breast pain for 4 or more weeks.
• Failure of oral antifungals and or antibiotics.
Treatment is both supportive and systemic and avoiding cold is key. She recalled a young mother who arrived in her office bundled up in a down parka on a warm California spring day. “I don’t know why, but this really seems to help,” she said.
“I suggest taking two hot showers a day and all the better if they can be right before nursing. Hot pads and compresses are not going to help. You need to warm up the entire body to calm this vascular reactivity.”
Women should also avoid consuming anything that can cause vasoconstriction, including caffeine and tobacco, she advised.
Nifedipine is a very effective medication, and is safe for nursing infants, Dr. Stone said. The sustained-released 30 mg/day dose is typically recommended, but she has changed her thinking on this a bit.
Her internal study showed that, although 83% responded very well to the drug, about a third of them also had a vasodilation-related side effect.
“For this reason, I usually now start with the 10 mg nonsustained form, and warn about things like headache, dizziness, postural hypotension, and fainting,” she said. Typically, patients adjust well to the drug’s effects and then the dose can be individually titrated.
Dr. Fullerton Stone had no relevant financial disclosures.
On Twitter @Alz_Gal
NEW YORK – The “perfect storm” of pregnancy and lactation can throw breastfeeding moms into a painful deep freeze.
Almost 25% of women with lactation pain may actually be experiencing symptoms of Raynaud’s, Dr. Honor Fullerton Stone said at the American Academy of Dermatology summer meeting.
“Breastfeeding mothers are in a perfect storm,” of physical developments that predispose them to this vasoconstrictive phenomenon, said Dr. Fullerton Stone, who practices dermatology in Menlo Park, Ca. “Estrogen increases the alpha-adrenergic receptors on smooth muscle. Nerve irritation from constant breastfeeding upregulates those receptors. And emotional stress – crying baby, anyone? – increases epinephrine, which contributes further to vasoconstriction.”
She conducted a review of 88 of her own patients with nursing-related breast pain. Of these, about a quarter ended up with a diagnosis of nipple vasoconstriction. None of the women had a history of Raynaud’s disease.
Pain during a nursing session is the presenting complaint, but breastfeeding pain is incredibly nonspecific as a symptom. It’s the quality of the pain, Dr Stone said, that should ring a bell.
“There’s let-down pain, which occurs at latch and then comes on again later, with refill. There’s pain from candidiasis, which is dramatic at latch, like a radiating heat, but goes away rapidly after a few days of antifungals,” she noted. But with Raynaud’s, “the pain is persistent. It’s throbbing, which makes sense since it’s vascular. And it’s constant,” lasting through every nursing session, which she said is the kind of experience that makes mothers stop breastfeeding.
Since pain is such a pervasive symptom in breastfeeding complaints, women with vasoconstriction of the nipple are often misdiagnosed. They can go for months trying to improve latch technique or receiving antifungal therapy with no improvement, she said.
Dr. Stone considers a diagnosis of Raynaud’s if two of the following criteria are met:
• Color change of nipple, cold sensitivity, or color change of acral surfaces with cold exposure.
• Chronic deep breast pain for 4 or more weeks.
• Failure of oral antifungals and or antibiotics.
Treatment is both supportive and systemic and avoiding cold is key. She recalled a young mother who arrived in her office bundled up in a down parka on a warm California spring day. “I don’t know why, but this really seems to help,” she said.
“I suggest taking two hot showers a day and all the better if they can be right before nursing. Hot pads and compresses are not going to help. You need to warm up the entire body to calm this vascular reactivity.”
Women should also avoid consuming anything that can cause vasoconstriction, including caffeine and tobacco, she advised.
Nifedipine is a very effective medication, and is safe for nursing infants, Dr. Stone said. The sustained-released 30 mg/day dose is typically recommended, but she has changed her thinking on this a bit.
Her internal study showed that, although 83% responded very well to the drug, about a third of them also had a vasodilation-related side effect.
“For this reason, I usually now start with the 10 mg nonsustained form, and warn about things like headache, dizziness, postural hypotension, and fainting,” she said. Typically, patients adjust well to the drug’s effects and then the dose can be individually titrated.
Dr. Fullerton Stone had no relevant financial disclosures.
On Twitter @Alz_Gal
NEW YORK – The “perfect storm” of pregnancy and lactation can throw breastfeeding moms into a painful deep freeze.
Almost 25% of women with lactation pain may actually be experiencing symptoms of Raynaud’s, Dr. Honor Fullerton Stone said at the American Academy of Dermatology summer meeting.
“Breastfeeding mothers are in a perfect storm,” of physical developments that predispose them to this vasoconstrictive phenomenon, said Dr. Fullerton Stone, who practices dermatology in Menlo Park, Ca. “Estrogen increases the alpha-adrenergic receptors on smooth muscle. Nerve irritation from constant breastfeeding upregulates those receptors. And emotional stress – crying baby, anyone? – increases epinephrine, which contributes further to vasoconstriction.”
She conducted a review of 88 of her own patients with nursing-related breast pain. Of these, about a quarter ended up with a diagnosis of nipple vasoconstriction. None of the women had a history of Raynaud’s disease.
Pain during a nursing session is the presenting complaint, but breastfeeding pain is incredibly nonspecific as a symptom. It’s the quality of the pain, Dr Stone said, that should ring a bell.
“There’s let-down pain, which occurs at latch and then comes on again later, with refill. There’s pain from candidiasis, which is dramatic at latch, like a radiating heat, but goes away rapidly after a few days of antifungals,” she noted. But with Raynaud’s, “the pain is persistent. It’s throbbing, which makes sense since it’s vascular. And it’s constant,” lasting through every nursing session, which she said is the kind of experience that makes mothers stop breastfeeding.
Since pain is such a pervasive symptom in breastfeeding complaints, women with vasoconstriction of the nipple are often misdiagnosed. They can go for months trying to improve latch technique or receiving antifungal therapy with no improvement, she said.
Dr. Stone considers a diagnosis of Raynaud’s if two of the following criteria are met:
• Color change of nipple, cold sensitivity, or color change of acral surfaces with cold exposure.
• Chronic deep breast pain for 4 or more weeks.
• Failure of oral antifungals and or antibiotics.
Treatment is both supportive and systemic and avoiding cold is key. She recalled a young mother who arrived in her office bundled up in a down parka on a warm California spring day. “I don’t know why, but this really seems to help,” she said.
“I suggest taking two hot showers a day and all the better if they can be right before nursing. Hot pads and compresses are not going to help. You need to warm up the entire body to calm this vascular reactivity.”
Women should also avoid consuming anything that can cause vasoconstriction, including caffeine and tobacco, she advised.
Nifedipine is a very effective medication, and is safe for nursing infants, Dr. Stone said. The sustained-released 30 mg/day dose is typically recommended, but she has changed her thinking on this a bit.
Her internal study showed that, although 83% responded very well to the drug, about a third of them also had a vasodilation-related side effect.
“For this reason, I usually now start with the 10 mg nonsustained form, and warn about things like headache, dizziness, postural hypotension, and fainting,” she said. Typically, patients adjust well to the drug’s effects and then the dose can be individually titrated.
Dr. Fullerton Stone had no relevant financial disclosures.
On Twitter @Alz_Gal
AT THE AAD SUMMER ACADEMY 2015
Early intervention may forestall menopause-related skin aging
NEW YORK – Evidence is mounting that early intervention in the menopausal transition could help forestall some of the skin aging associated with estrogen decline.
Estrogen supplementation and collagen stimulation both seem effective in preserving the integrity of a woman’s skin as levels of the hormone decrease, Dr. Diane Madfes said at the American Academy of Dermatology summer meeting.
Type 3 collagen decreases by up to 50% within a few years of menopause, said Dr. Madfes, a dermatologist in New York. This is directly related to a loss of estrogen receptor beta in the dermal matrix, which promotes collagen formation.
“There is a theory – the timing hypothesis – that we have a window of opportunity to intervene. If we can stimulate the collagen before the receptors go down, maybe we can have a beneficial effect on skin.”
Any method of collagen stimulation should work, she said: laser resurfacing, microneedling, or radiofrequency. “We are very good about being able to stimulate collagen. The method doesn’t matter as much as the timing. The important thing is to intervene early. If you see your patients starting to sag, see a loss of elasticity, that is the time to intervene. Get at the collagen while it’s still receptive.”
Estrogen exerts a plethora of antiaging, skin-preserving effects. “We know that a decrease in estrogen is related to telomere shortening. Estrogen protects against oxidative damage. It signals keratinocytes through IGF-1,” she said.
The hormone also protects skin’s water-binding qualities by promoting mucopolysaccharides, sebum production, barrier function, and hyaluronic acid. It may even play a role in protecting against ultraviolet light. Estrogen downregulation affects healing by inhibiting the proliferation of keratinocytes and the proliferation and migration of fibroblasts.
All these add up to rapid skin aging after estrogen levels drop.
“The visible effects of aging on women’s skin are not so much related to her chronological age as to the years after menopause,” Dr. Madfes said – a finding that is particularly illustrated in young women with surgical menopause and those with breast cancer who take tamoxifen. The observation seems to suggest that early intervention with estrogen might help prevent at least some of the signs of aging.
The ongoing KEEPS trial (Kronos Early Estrogen Prevention Study) may shed some light on the issue. KEEPS has randomized 729 women aged 42-58 years to oral or transdermal estrogen; the primary endpoint is rate of atherosclerosis. But an ancillary study is looking at the effect of estrogen on skin wrinkles and skin rigidity.
The substudy is based on positive findings of a 1996 study, which found evidence for facial application of topical estrogen designed for vulvar use. After 6 months, elasticity and firmness significantly improved. Skin moisture increased, as did type 3 collagen and collagen fibers.
Some women do use topical estrogens on their faces. “It seems to promote skin thickening and tightening,“ Dr. Madfes said, although a recent editorial suggested that using the product anywhere but on the genitals can cause estrogen-mediated side effects in both children and pets.
But recommending estrogen is fraught with controversy. Large studies have come to conflicting conclusions about its benefit and safety. And prescribing estrogen is not really within a dermatologist’s purview.
“It’s not for us to suggest that women go on hormone therapy. But we can explain these things and ask if she is taking it, or if she’s talked to her gynecologist about it.”
Dr. Madfes has no financial disclosures to report.
On Twitter @Alz_Gal
NEW YORK – Evidence is mounting that early intervention in the menopausal transition could help forestall some of the skin aging associated with estrogen decline.
Estrogen supplementation and collagen stimulation both seem effective in preserving the integrity of a woman’s skin as levels of the hormone decrease, Dr. Diane Madfes said at the American Academy of Dermatology summer meeting.
Type 3 collagen decreases by up to 50% within a few years of menopause, said Dr. Madfes, a dermatologist in New York. This is directly related to a loss of estrogen receptor beta in the dermal matrix, which promotes collagen formation.
“There is a theory – the timing hypothesis – that we have a window of opportunity to intervene. If we can stimulate the collagen before the receptors go down, maybe we can have a beneficial effect on skin.”
Any method of collagen stimulation should work, she said: laser resurfacing, microneedling, or radiofrequency. “We are very good about being able to stimulate collagen. The method doesn’t matter as much as the timing. The important thing is to intervene early. If you see your patients starting to sag, see a loss of elasticity, that is the time to intervene. Get at the collagen while it’s still receptive.”
Estrogen exerts a plethora of antiaging, skin-preserving effects. “We know that a decrease in estrogen is related to telomere shortening. Estrogen protects against oxidative damage. It signals keratinocytes through IGF-1,” she said.
The hormone also protects skin’s water-binding qualities by promoting mucopolysaccharides, sebum production, barrier function, and hyaluronic acid. It may even play a role in protecting against ultraviolet light. Estrogen downregulation affects healing by inhibiting the proliferation of keratinocytes and the proliferation and migration of fibroblasts.
All these add up to rapid skin aging after estrogen levels drop.
“The visible effects of aging on women’s skin are not so much related to her chronological age as to the years after menopause,” Dr. Madfes said – a finding that is particularly illustrated in young women with surgical menopause and those with breast cancer who take tamoxifen. The observation seems to suggest that early intervention with estrogen might help prevent at least some of the signs of aging.
The ongoing KEEPS trial (Kronos Early Estrogen Prevention Study) may shed some light on the issue. KEEPS has randomized 729 women aged 42-58 years to oral or transdermal estrogen; the primary endpoint is rate of atherosclerosis. But an ancillary study is looking at the effect of estrogen on skin wrinkles and skin rigidity.
The substudy is based on positive findings of a 1996 study, which found evidence for facial application of topical estrogen designed for vulvar use. After 6 months, elasticity and firmness significantly improved. Skin moisture increased, as did type 3 collagen and collagen fibers.
Some women do use topical estrogens on their faces. “It seems to promote skin thickening and tightening,“ Dr. Madfes said, although a recent editorial suggested that using the product anywhere but on the genitals can cause estrogen-mediated side effects in both children and pets.
But recommending estrogen is fraught with controversy. Large studies have come to conflicting conclusions about its benefit and safety. And prescribing estrogen is not really within a dermatologist’s purview.
“It’s not for us to suggest that women go on hormone therapy. But we can explain these things and ask if she is taking it, or if she’s talked to her gynecologist about it.”
Dr. Madfes has no financial disclosures to report.
On Twitter @Alz_Gal
NEW YORK – Evidence is mounting that early intervention in the menopausal transition could help forestall some of the skin aging associated with estrogen decline.
Estrogen supplementation and collagen stimulation both seem effective in preserving the integrity of a woman’s skin as levels of the hormone decrease, Dr. Diane Madfes said at the American Academy of Dermatology summer meeting.
Type 3 collagen decreases by up to 50% within a few years of menopause, said Dr. Madfes, a dermatologist in New York. This is directly related to a loss of estrogen receptor beta in the dermal matrix, which promotes collagen formation.
“There is a theory – the timing hypothesis – that we have a window of opportunity to intervene. If we can stimulate the collagen before the receptors go down, maybe we can have a beneficial effect on skin.”
Any method of collagen stimulation should work, she said: laser resurfacing, microneedling, or radiofrequency. “We are very good about being able to stimulate collagen. The method doesn’t matter as much as the timing. The important thing is to intervene early. If you see your patients starting to sag, see a loss of elasticity, that is the time to intervene. Get at the collagen while it’s still receptive.”
Estrogen exerts a plethora of antiaging, skin-preserving effects. “We know that a decrease in estrogen is related to telomere shortening. Estrogen protects against oxidative damage. It signals keratinocytes through IGF-1,” she said.
The hormone also protects skin’s water-binding qualities by promoting mucopolysaccharides, sebum production, barrier function, and hyaluronic acid. It may even play a role in protecting against ultraviolet light. Estrogen downregulation affects healing by inhibiting the proliferation of keratinocytes and the proliferation and migration of fibroblasts.
All these add up to rapid skin aging after estrogen levels drop.
“The visible effects of aging on women’s skin are not so much related to her chronological age as to the years after menopause,” Dr. Madfes said – a finding that is particularly illustrated in young women with surgical menopause and those with breast cancer who take tamoxifen. The observation seems to suggest that early intervention with estrogen might help prevent at least some of the signs of aging.
The ongoing KEEPS trial (Kronos Early Estrogen Prevention Study) may shed some light on the issue. KEEPS has randomized 729 women aged 42-58 years to oral or transdermal estrogen; the primary endpoint is rate of atherosclerosis. But an ancillary study is looking at the effect of estrogen on skin wrinkles and skin rigidity.
The substudy is based on positive findings of a 1996 study, which found evidence for facial application of topical estrogen designed for vulvar use. After 6 months, elasticity and firmness significantly improved. Skin moisture increased, as did type 3 collagen and collagen fibers.
Some women do use topical estrogens on their faces. “It seems to promote skin thickening and tightening,“ Dr. Madfes said, although a recent editorial suggested that using the product anywhere but on the genitals can cause estrogen-mediated side effects in both children and pets.
But recommending estrogen is fraught with controversy. Large studies have come to conflicting conclusions about its benefit and safety. And prescribing estrogen is not really within a dermatologist’s purview.
“It’s not for us to suggest that women go on hormone therapy. But we can explain these things and ask if she is taking it, or if she’s talked to her gynecologist about it.”
Dr. Madfes has no financial disclosures to report.
On Twitter @Alz_Gal
EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2015
AAIC: Aerobic exercise proves beneficial for mild cognitive impairment
WASHINGTON – For the first time, a randomized study has demonstrated that vigorous physical exercise not only improves cognition, but moves Alzheimer’s disease biomarkers in the right direction.
Six months after subjects with mild cognitive impairment (MCI) began aerobic exercise, scores on a composite measure of cognition rose significantly. Not only that, hypometabolic brain regions associated with Alzheimer’s symptoms were reperfused. And phosphorylated tau – a marker of neuronal injury – fell significantly in cerebrospinal fluid (CSF), Laura Baker, Ph.D., said at the Alzheimer’s Association International Conference 2015.
The finding of reduced tau is especially intriguing, said Dr. Baker of Wake Forest University, Winston-Salem, N.C. The biggest improvements occurred in subjects older than 70 years, who were carrying a double hit of both MCI- and age-related tau.
“I hope that we are moving toward being able to demonstrate that regular, moderate aerobic exercise can attenuate the effects of both aging and Alzheimer’s. This is a potential intervention that combats two diseases – if we regard aging as a disease process.”
Aerobic exercise is easy to institute, inexpensive to continue, and confers numerous physical and mental benefits, Dr. Baker said.
“Like other lifestyle interventions, exercise targets multiple, health-restoring biological processes. It’s not just one molecule affecting one part of our chemistry, but multiple targets. These kinds of interventions with diversified target portfolios may be our most potent means to prevent and slow Alzheimer’s.”
She and her colleagues conducted a 6-month exercise trial with 71 sedentary adults who had both MCI and prediabetes (hemoglobin A1c of 5.7%-6.4%). The subjects, aged 55-89 years, were randomized to either a control program of thrice-weekly stretching, or to an exercise program of thrice-weekly aerobic exercise for 45-60 minutes. Most subjects used a treadmill, but other forms of exercise were also allowed, including stationary bike and approved group classes.
The intervention group aimed to maintain an exertion level of 70%-80% of their maximum heart rate, while the control group exercised at below 35% of it. Both interventions were carried out under the supervision of a study researcher. This is an important point, Dr. Baker noted, because it means that both groups were getting the benefit of leaving their house several times a week and experiencing social interactions in classes at the gym.
At baseline and 6 months, everyone completed cognitive testing (verbal recall, tests of executive function); a 400-meter timed walking test; glucose tolerance test; body fat assessment; and blood and CSF collection. A total of 40 also underwent structural and functional brain MRI. All results were controlled for age and education.
For the analysis, Dr. Baker stratified the group by those younger and older than 70 years.
There were no reductions in CSF tau in either age group in the stretching cohort. However, in the exercise cohort, both age groups experienced significant declines in CSF tau. Tau is released when neurons are damaged; reductions in tau suggest a slowing of that damage. The older group’s tau levels declined by 10 pg/mL – especially impressive when considering that their baseline levels were elevated not only from their cognitive disorder, but from normal aging.
“In fact, the greatest drops in tau occurred among the folks who were starting with the highest levels,” Dr. Baker said.
She found a trend – albeit nonsignificant – for a positive change in CSF amyloid-beta-42 among the intervention group. “In the stretching group, we expected to see continuation of disease, and this was reflected in the CSF amyloid levels, which increased over 6 months. In the aerobic group, this increase appeared to be attenuated.”
Whole brain blood flow also improved significantly in the exercise group and was driven by increased flow in regions particularly associated with aging and Alzheimer’s: the superior frontal cortex, posterior cingulate, and cingulate gyrus.
“In all three regions blood flow was increased bilaterally, and these increases were similar. This was encouraging and suggests that changes related to aging and Alzheimer’s benefited. Typically, the signature profile of aging is reduced flow in the superior frontal region, and the profile for Alzheimer’s is reduced flow in the posterior cingulate and cingulate gyrus. These are exactly the regions that were boosted by exercise.”
The cognitive measure was a compilation of several tests of executive function. “Independent of age and APOE4 [apolipoprotein E epsilon-4] status, we saw significantly improved performance.”
Dr. Baker said that she is eager to follow-up with her cohort and find out not only how many have independently continued to exercise, but to retest them and see if the effects were transient or imparted some lasting benefit. She also plans to initiate an 18-month, phase III trial of the two interventions at 15 sites throughout the United States.
“We really hope these results will help us move this work forward,” she said.
Dr. Baker had no financial disclosures.
On Twitter @alz_gal
WASHINGTON – For the first time, a randomized study has demonstrated that vigorous physical exercise not only improves cognition, but moves Alzheimer’s disease biomarkers in the right direction.
Six months after subjects with mild cognitive impairment (MCI) began aerobic exercise, scores on a composite measure of cognition rose significantly. Not only that, hypometabolic brain regions associated with Alzheimer’s symptoms were reperfused. And phosphorylated tau – a marker of neuronal injury – fell significantly in cerebrospinal fluid (CSF), Laura Baker, Ph.D., said at the Alzheimer’s Association International Conference 2015.
The finding of reduced tau is especially intriguing, said Dr. Baker of Wake Forest University, Winston-Salem, N.C. The biggest improvements occurred in subjects older than 70 years, who were carrying a double hit of both MCI- and age-related tau.
“I hope that we are moving toward being able to demonstrate that regular, moderate aerobic exercise can attenuate the effects of both aging and Alzheimer’s. This is a potential intervention that combats two diseases – if we regard aging as a disease process.”
Aerobic exercise is easy to institute, inexpensive to continue, and confers numerous physical and mental benefits, Dr. Baker said.
“Like other lifestyle interventions, exercise targets multiple, health-restoring biological processes. It’s not just one molecule affecting one part of our chemistry, but multiple targets. These kinds of interventions with diversified target portfolios may be our most potent means to prevent and slow Alzheimer’s.”
She and her colleagues conducted a 6-month exercise trial with 71 sedentary adults who had both MCI and prediabetes (hemoglobin A1c of 5.7%-6.4%). The subjects, aged 55-89 years, were randomized to either a control program of thrice-weekly stretching, or to an exercise program of thrice-weekly aerobic exercise for 45-60 minutes. Most subjects used a treadmill, but other forms of exercise were also allowed, including stationary bike and approved group classes.
The intervention group aimed to maintain an exertion level of 70%-80% of their maximum heart rate, while the control group exercised at below 35% of it. Both interventions were carried out under the supervision of a study researcher. This is an important point, Dr. Baker noted, because it means that both groups were getting the benefit of leaving their house several times a week and experiencing social interactions in classes at the gym.
At baseline and 6 months, everyone completed cognitive testing (verbal recall, tests of executive function); a 400-meter timed walking test; glucose tolerance test; body fat assessment; and blood and CSF collection. A total of 40 also underwent structural and functional brain MRI. All results were controlled for age and education.
For the analysis, Dr. Baker stratified the group by those younger and older than 70 years.
There were no reductions in CSF tau in either age group in the stretching cohort. However, in the exercise cohort, both age groups experienced significant declines in CSF tau. Tau is released when neurons are damaged; reductions in tau suggest a slowing of that damage. The older group’s tau levels declined by 10 pg/mL – especially impressive when considering that their baseline levels were elevated not only from their cognitive disorder, but from normal aging.
“In fact, the greatest drops in tau occurred among the folks who were starting with the highest levels,” Dr. Baker said.
She found a trend – albeit nonsignificant – for a positive change in CSF amyloid-beta-42 among the intervention group. “In the stretching group, we expected to see continuation of disease, and this was reflected in the CSF amyloid levels, which increased over 6 months. In the aerobic group, this increase appeared to be attenuated.”
Whole brain blood flow also improved significantly in the exercise group and was driven by increased flow in regions particularly associated with aging and Alzheimer’s: the superior frontal cortex, posterior cingulate, and cingulate gyrus.
“In all three regions blood flow was increased bilaterally, and these increases were similar. This was encouraging and suggests that changes related to aging and Alzheimer’s benefited. Typically, the signature profile of aging is reduced flow in the superior frontal region, and the profile for Alzheimer’s is reduced flow in the posterior cingulate and cingulate gyrus. These are exactly the regions that were boosted by exercise.”
The cognitive measure was a compilation of several tests of executive function. “Independent of age and APOE4 [apolipoprotein E epsilon-4] status, we saw significantly improved performance.”
Dr. Baker said that she is eager to follow-up with her cohort and find out not only how many have independently continued to exercise, but to retest them and see if the effects were transient or imparted some lasting benefit. She also plans to initiate an 18-month, phase III trial of the two interventions at 15 sites throughout the United States.
“We really hope these results will help us move this work forward,” she said.
Dr. Baker had no financial disclosures.
On Twitter @alz_gal
WASHINGTON – For the first time, a randomized study has demonstrated that vigorous physical exercise not only improves cognition, but moves Alzheimer’s disease biomarkers in the right direction.
Six months after subjects with mild cognitive impairment (MCI) began aerobic exercise, scores on a composite measure of cognition rose significantly. Not only that, hypometabolic brain regions associated with Alzheimer’s symptoms were reperfused. And phosphorylated tau – a marker of neuronal injury – fell significantly in cerebrospinal fluid (CSF), Laura Baker, Ph.D., said at the Alzheimer’s Association International Conference 2015.
The finding of reduced tau is especially intriguing, said Dr. Baker of Wake Forest University, Winston-Salem, N.C. The biggest improvements occurred in subjects older than 70 years, who were carrying a double hit of both MCI- and age-related tau.
“I hope that we are moving toward being able to demonstrate that regular, moderate aerobic exercise can attenuate the effects of both aging and Alzheimer’s. This is a potential intervention that combats two diseases – if we regard aging as a disease process.”
Aerobic exercise is easy to institute, inexpensive to continue, and confers numerous physical and mental benefits, Dr. Baker said.
“Like other lifestyle interventions, exercise targets multiple, health-restoring biological processes. It’s not just one molecule affecting one part of our chemistry, but multiple targets. These kinds of interventions with diversified target portfolios may be our most potent means to prevent and slow Alzheimer’s.”
She and her colleagues conducted a 6-month exercise trial with 71 sedentary adults who had both MCI and prediabetes (hemoglobin A1c of 5.7%-6.4%). The subjects, aged 55-89 years, were randomized to either a control program of thrice-weekly stretching, or to an exercise program of thrice-weekly aerobic exercise for 45-60 minutes. Most subjects used a treadmill, but other forms of exercise were also allowed, including stationary bike and approved group classes.
The intervention group aimed to maintain an exertion level of 70%-80% of their maximum heart rate, while the control group exercised at below 35% of it. Both interventions were carried out under the supervision of a study researcher. This is an important point, Dr. Baker noted, because it means that both groups were getting the benefit of leaving their house several times a week and experiencing social interactions in classes at the gym.
At baseline and 6 months, everyone completed cognitive testing (verbal recall, tests of executive function); a 400-meter timed walking test; glucose tolerance test; body fat assessment; and blood and CSF collection. A total of 40 also underwent structural and functional brain MRI. All results were controlled for age and education.
For the analysis, Dr. Baker stratified the group by those younger and older than 70 years.
There were no reductions in CSF tau in either age group in the stretching cohort. However, in the exercise cohort, both age groups experienced significant declines in CSF tau. Tau is released when neurons are damaged; reductions in tau suggest a slowing of that damage. The older group’s tau levels declined by 10 pg/mL – especially impressive when considering that their baseline levels were elevated not only from their cognitive disorder, but from normal aging.
“In fact, the greatest drops in tau occurred among the folks who were starting with the highest levels,” Dr. Baker said.
She found a trend – albeit nonsignificant – for a positive change in CSF amyloid-beta-42 among the intervention group. “In the stretching group, we expected to see continuation of disease, and this was reflected in the CSF amyloid levels, which increased over 6 months. In the aerobic group, this increase appeared to be attenuated.”
Whole brain blood flow also improved significantly in the exercise group and was driven by increased flow in regions particularly associated with aging and Alzheimer’s: the superior frontal cortex, posterior cingulate, and cingulate gyrus.
“In all three regions blood flow was increased bilaterally, and these increases were similar. This was encouraging and suggests that changes related to aging and Alzheimer’s benefited. Typically, the signature profile of aging is reduced flow in the superior frontal region, and the profile for Alzheimer’s is reduced flow in the posterior cingulate and cingulate gyrus. These are exactly the regions that were boosted by exercise.”
The cognitive measure was a compilation of several tests of executive function. “Independent of age and APOE4 [apolipoprotein E epsilon-4] status, we saw significantly improved performance.”
Dr. Baker said that she is eager to follow-up with her cohort and find out not only how many have independently continued to exercise, but to retest them and see if the effects were transient or imparted some lasting benefit. She also plans to initiate an 18-month, phase III trial of the two interventions at 15 sites throughout the United States.
“We really hope these results will help us move this work forward,” she said.
Dr. Baker had no financial disclosures.
On Twitter @alz_gal
AT AAIC 2015
Key clinical point: Regular aerobic exercise boosted cognition and blood flow to the brain, and improved cerebrospinal biomarkers associated with Alzheimer’s disease.
Major finding: Phosphorylated tau in cerebrospinal fluid decreased by 10 pg/mL in the group that exercised vigorously.
Data source: The 6-month study randomized 71 adults with MCI and prediabetes to either thrice-weekly stretching or aerobic exercise.
Disclosures: Dr. Baker had no financial conflicts.
Online resource provides updated HCV tx guidelines
The newest guidelines for testing, managing, and treating hepatitis C infections in adults are part of a “living document” – a constantly updated online resource that reflects the ever-changing world of HCV research.
A joint venture of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), the document puts cutting-edge science in the hands of clinicians, Dr. Gary L. Davis wrote (Hepatology 2015 June 25 [doi:10.1002/hep.27950]). The continuously updated version may be accessed at any time at www.hcvguidelines.org.
“The pace of hepatitis C virus (HCV) drug development in recent years has accelerated dramatically,” wrote Dr. Davis, cochair for the AASLD/IDSA HCV Guidance writing group. “Such information and advice can be difficult to access readily given the diverse sources from which information is available, and the sometimes lengthy time needed for publication of original articles and scholarly perspectives. Traditional practice guidelines for more established areas of medicine and care often take years to develop and bring to publication. In the new era in hepatitis C treatment, such a process would not be nimble or timely enough to address the needs of patients with HCV infection, practitioners caring for these patients, or payers approving therapies for use.”
The online guidelines “will undergo real-time revisions as the field evolves,” Dr. Davis noted. A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations.
The new update contains recommendations for direct antiviral drug regimens in treatment-naive patients and for all six HCV genotypes. A second section examines the recommended regimens for patients who have failed treatment with PEG-interferon and ribavirin, with or without a direct antiviral agent.
The document also gives guidance for managing patients with and without a sustained viral response and concludes with a section on treating special patient populations (decompensated cirrhosis, post-transplant HCV infections, renal impairment, and coinfection with HIV).
[email protected]
AGA Resource
AGA offers a Hepatitis C Clinical Service Line through the AGA Roadmap to the Future of Practice to help you provide high-quality patient care. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
The newest guidelines for testing, managing, and treating hepatitis C infections in adults are part of a “living document” – a constantly updated online resource that reflects the ever-changing world of HCV research.
A joint venture of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), the document puts cutting-edge science in the hands of clinicians, Dr. Gary L. Davis wrote (Hepatology 2015 June 25 [doi:10.1002/hep.27950]). The continuously updated version may be accessed at any time at www.hcvguidelines.org.
“The pace of hepatitis C virus (HCV) drug development in recent years has accelerated dramatically,” wrote Dr. Davis, cochair for the AASLD/IDSA HCV Guidance writing group. “Such information and advice can be difficult to access readily given the diverse sources from which information is available, and the sometimes lengthy time needed for publication of original articles and scholarly perspectives. Traditional practice guidelines for more established areas of medicine and care often take years to develop and bring to publication. In the new era in hepatitis C treatment, such a process would not be nimble or timely enough to address the needs of patients with HCV infection, practitioners caring for these patients, or payers approving therapies for use.”
The online guidelines “will undergo real-time revisions as the field evolves,” Dr. Davis noted. A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations.
The new update contains recommendations for direct antiviral drug regimens in treatment-naive patients and for all six HCV genotypes. A second section examines the recommended regimens for patients who have failed treatment with PEG-interferon and ribavirin, with or without a direct antiviral agent.
The document also gives guidance for managing patients with and without a sustained viral response and concludes with a section on treating special patient populations (decompensated cirrhosis, post-transplant HCV infections, renal impairment, and coinfection with HIV).
[email protected]
AGA Resource
AGA offers a Hepatitis C Clinical Service Line through the AGA Roadmap to the Future of Practice to help you provide high-quality patient care. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
The newest guidelines for testing, managing, and treating hepatitis C infections in adults are part of a “living document” – a constantly updated online resource that reflects the ever-changing world of HCV research.
A joint venture of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), the document puts cutting-edge science in the hands of clinicians, Dr. Gary L. Davis wrote (Hepatology 2015 June 25 [doi:10.1002/hep.27950]). The continuously updated version may be accessed at any time at www.hcvguidelines.org.
“The pace of hepatitis C virus (HCV) drug development in recent years has accelerated dramatically,” wrote Dr. Davis, cochair for the AASLD/IDSA HCV Guidance writing group. “Such information and advice can be difficult to access readily given the diverse sources from which information is available, and the sometimes lengthy time needed for publication of original articles and scholarly perspectives. Traditional practice guidelines for more established areas of medicine and care often take years to develop and bring to publication. In the new era in hepatitis C treatment, such a process would not be nimble or timely enough to address the needs of patients with HCV infection, practitioners caring for these patients, or payers approving therapies for use.”
The online guidelines “will undergo real-time revisions as the field evolves,” Dr. Davis noted. A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations.
The new update contains recommendations for direct antiviral drug regimens in treatment-naive patients and for all six HCV genotypes. A second section examines the recommended regimens for patients who have failed treatment with PEG-interferon and ribavirin, with or without a direct antiviral agent.
The document also gives guidance for managing patients with and without a sustained viral response and concludes with a section on treating special patient populations (decompensated cirrhosis, post-transplant HCV infections, renal impairment, and coinfection with HIV).
[email protected]
AGA Resource
AGA offers a Hepatitis C Clinical Service Line through the AGA Roadmap to the Future of Practice to help you provide high-quality patient care. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
VIDEO: Keeping the Alzheimer’s big picture in mind as antiamyloid trials continue
WASHINGTON – Amyloid-beta has been the Alzheimer’s research darling for more than a decade, and finally, after many failures, some small successes may be appearing in antiamyloid trials.
Experts suggest that these encouraging early results may lead companies to retest failed drugs under new conditions – for example, by using patients who test positive for amyloid-beta on brain PET scans, who have prodromal disease, or who are asymptomatic.
But questions remain, and some are fundamental. The functional nature of amyloid remains unknown. There are still questions about which form is the most neurotoxic. Little is understood about the way it interacts with tau as symptoms emerge.
Will these lines of investigation fall to the wayside if companies and amyloid-centric researchers put too many eggs into the antiamyloid basket? Dr. Michael Wolfe, Ph.D., of Brigham and Women’s Hospital, Boston, discusses these issues in an interview.
On Twitter @alz_gal
WASHINGTON – Amyloid-beta has been the Alzheimer’s research darling for more than a decade, and finally, after many failures, some small successes may be appearing in antiamyloid trials.
Experts suggest that these encouraging early results may lead companies to retest failed drugs under new conditions – for example, by using patients who test positive for amyloid-beta on brain PET scans, who have prodromal disease, or who are asymptomatic.
But questions remain, and some are fundamental. The functional nature of amyloid remains unknown. There are still questions about which form is the most neurotoxic. Little is understood about the way it interacts with tau as symptoms emerge.
Will these lines of investigation fall to the wayside if companies and amyloid-centric researchers put too many eggs into the antiamyloid basket? Dr. Michael Wolfe, Ph.D., of Brigham and Women’s Hospital, Boston, discusses these issues in an interview.
On Twitter @alz_gal
WASHINGTON – Amyloid-beta has been the Alzheimer’s research darling for more than a decade, and finally, after many failures, some small successes may be appearing in antiamyloid trials.
Experts suggest that these encouraging early results may lead companies to retest failed drugs under new conditions – for example, by using patients who test positive for amyloid-beta on brain PET scans, who have prodromal disease, or who are asymptomatic.
But questions remain, and some are fundamental. The functional nature of amyloid remains unknown. There are still questions about which form is the most neurotoxic. Little is understood about the way it interacts with tau as symptoms emerge.
Will these lines of investigation fall to the wayside if companies and amyloid-centric researchers put too many eggs into the antiamyloid basket? Dr. Michael Wolfe, Ph.D., of Brigham and Women’s Hospital, Boston, discusses these issues in an interview.
On Twitter @alz_gal
AT AAIC 2015
Biogen’s aducanumab stumbles on cognitive endpoints at 6 mg/kg dose
WASHINGTON – An antiamyloid antibody that showed significant cognitive benefit at 10 mg/kg failed to deliver similar good news at a lower dose in the first randomized, antiamyloid antibody trial comprising only patients who screened positive for amyloid-beta plaques on PET imaging.
At 6 mg/kg, aducanumab, a fully human monoclonal antibody, cleared amyloid brain plaques almost as well as the higher dose. But although there were numerical improvements on cognitive measures, these were not statistically significant, Dr. Jeff Sevigny said at the Alzheimer’s Association International Conference 2015.
The drug is being developed by Biogen. Dr. Sevigny is the company’s senior medical director of neurodegenerative disorders.
The PRIME study enrolled 166 patients with prodromal or mild Alzheimer’s who screened positive for amyloid-beta plaques on PET imaging. This ensured a pure cohort of patients with amyloid-beta plaques – something that has been lacking in antiamyloid antibody trials. Some researchers have estimated that up to 15% of those enrolled in previous trials actually had no amyloid-beta in the brain, a finding that could seriously dilute any efficacy signal of a drug designed to remove the protein.
The 52-week phase Ib study randomized patients to placebo or to 1-, 3-, 6-, or 10-mg/kg monthly infusions of aducanumab. In all, patients received 14 infusions. While the trial was designed to evaluate safety and tolerability, it did include preliminary cognitive data in the form of the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB).
The initial study readout was reported in March amid global hoopla. The 3- and 10-mg/kg doses removed amyloid-beta from the brain; the 10-mg/kg dose delivered significant benefits on both cognitive measures. Patients taking the 10-mg/kg dose dipped about half a point below baseline on the MMSE, compared with nearly a 3-point drop for those on placebo. The 3-mg/kg dose also conferred significant benefits against cognitive decline.
Aducanumab was hailed as what could be the “Goldilocks drug” for Alzheimer’s – the first evidence of an antibody that both engaged the amyloid-beta target and provided significant cognitive improvements, although some researchers cautioned against overinterpretation of such early-phase results.
Patients in PRIME had a mean MMSE of 25, and about two-thirds were apolipoprotein E–epsilon 4 (APOE4) positive. Close to half were in the prodromal stage and the remainder had mild Alzheimer’s.
At 52 weeks, patients taking placebo worsened by 2.81 points on the MMSE. Patients taking 6 mg/kg lost 1.96 points – not a significant difference. The 10-mg/kg MMSE results were statistically significant, with a decline of 0.56 in the active group. Even the 3-mg/kg dose performed better than 6 mg/kg, with a decline of 0.70 points – significantly better than the placebo group.
The story was similar on the CDR-SB measure. The placebo group worsened by 1.87 points at week 52, while the 6-mg/kg group worsened by 1.11 points – again not statistically significant. Only the 10-mg/kg dose achieved a statistically significant difference relative to placebo (0.63 points). The 1-mg/kg dose was not significantly better than placebo on either the MMSE or CDR-SB.
All doses except for 1 mg/kg lowered amyloid-beta plaque burden. In the placebo arm, the level of amyloid remained unchanged at both imaging time points (26 and 52 weeks). Plaque moved out in a dose- and time-dependent manner, with 6 and 10 mg/kg removing increasing amounts of the protein.
Amyloid-related imaging abnormalities (ARIA), a brain inflammation related to the removal of amyloid plaques, occurred in 13% of the 3-mg/kg group, 33% of the 6-mg/kg group; and 47% of the 10-mg/kg group. Most of these (89%) occurred in the initial 5 weeks; most (65%) were asymptomatic. The remainder caused mild and transient symptoms, with headache, visual disturbances, and cognitive worsening that resolved by 12 weeks.
APOE4 carriers were particularly subject to ARIA. It occurred in 5% of patients taking the 1-mg/kg and 3-mg/kg doses, 43% of those taking 6 mg/kg, and 55% of those receiving 10 mg/kg. In noncarriers, there were no cases in the 1-mg/kg group. The incidence was 9%, 11%, and 17% in the 3-, 6-, and 10-mg/kg groups of noncarriers respectively. Patients who developed ARIA had the choice of dropping out, opting for a lower dose, or continuing the study at their original dose. Most who developed ARIA (56%) chose to continue treatment.
There were three deaths: two in the placebo group and one in the 10-mg/kg group. None were related to the study drug.
According to Biogen, aducanumab is a fully human IgG1 monoclonal antibody that binds aggregated forms of amyloid, not monomer, and preferentially attaches to parenchymal amyloid rather than vascular amyloid. It was “derived from a deidentified library of B cells collected from healthy elderly subjects with no signs of cognitive impairment and cognitively impaired elderly subjects with unusually slow cognitive decline.”
On Twitter @Alz_Gal
WASHINGTON – An antiamyloid antibody that showed significant cognitive benefit at 10 mg/kg failed to deliver similar good news at a lower dose in the first randomized, antiamyloid antibody trial comprising only patients who screened positive for amyloid-beta plaques on PET imaging.
At 6 mg/kg, aducanumab, a fully human monoclonal antibody, cleared amyloid brain plaques almost as well as the higher dose. But although there were numerical improvements on cognitive measures, these were not statistically significant, Dr. Jeff Sevigny said at the Alzheimer’s Association International Conference 2015.
The drug is being developed by Biogen. Dr. Sevigny is the company’s senior medical director of neurodegenerative disorders.
The PRIME study enrolled 166 patients with prodromal or mild Alzheimer’s who screened positive for amyloid-beta plaques on PET imaging. This ensured a pure cohort of patients with amyloid-beta plaques – something that has been lacking in antiamyloid antibody trials. Some researchers have estimated that up to 15% of those enrolled in previous trials actually had no amyloid-beta in the brain, a finding that could seriously dilute any efficacy signal of a drug designed to remove the protein.
The 52-week phase Ib study randomized patients to placebo or to 1-, 3-, 6-, or 10-mg/kg monthly infusions of aducanumab. In all, patients received 14 infusions. While the trial was designed to evaluate safety and tolerability, it did include preliminary cognitive data in the form of the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB).
The initial study readout was reported in March amid global hoopla. The 3- and 10-mg/kg doses removed amyloid-beta from the brain; the 10-mg/kg dose delivered significant benefits on both cognitive measures. Patients taking the 10-mg/kg dose dipped about half a point below baseline on the MMSE, compared with nearly a 3-point drop for those on placebo. The 3-mg/kg dose also conferred significant benefits against cognitive decline.
Aducanumab was hailed as what could be the “Goldilocks drug” for Alzheimer’s – the first evidence of an antibody that both engaged the amyloid-beta target and provided significant cognitive improvements, although some researchers cautioned against overinterpretation of such early-phase results.
Patients in PRIME had a mean MMSE of 25, and about two-thirds were apolipoprotein E–epsilon 4 (APOE4) positive. Close to half were in the prodromal stage and the remainder had mild Alzheimer’s.
At 52 weeks, patients taking placebo worsened by 2.81 points on the MMSE. Patients taking 6 mg/kg lost 1.96 points – not a significant difference. The 10-mg/kg MMSE results were statistically significant, with a decline of 0.56 in the active group. Even the 3-mg/kg dose performed better than 6 mg/kg, with a decline of 0.70 points – significantly better than the placebo group.
The story was similar on the CDR-SB measure. The placebo group worsened by 1.87 points at week 52, while the 6-mg/kg group worsened by 1.11 points – again not statistically significant. Only the 10-mg/kg dose achieved a statistically significant difference relative to placebo (0.63 points). The 1-mg/kg dose was not significantly better than placebo on either the MMSE or CDR-SB.
All doses except for 1 mg/kg lowered amyloid-beta plaque burden. In the placebo arm, the level of amyloid remained unchanged at both imaging time points (26 and 52 weeks). Plaque moved out in a dose- and time-dependent manner, with 6 and 10 mg/kg removing increasing amounts of the protein.
Amyloid-related imaging abnormalities (ARIA), a brain inflammation related to the removal of amyloid plaques, occurred in 13% of the 3-mg/kg group, 33% of the 6-mg/kg group; and 47% of the 10-mg/kg group. Most of these (89%) occurred in the initial 5 weeks; most (65%) were asymptomatic. The remainder caused mild and transient symptoms, with headache, visual disturbances, and cognitive worsening that resolved by 12 weeks.
APOE4 carriers were particularly subject to ARIA. It occurred in 5% of patients taking the 1-mg/kg and 3-mg/kg doses, 43% of those taking 6 mg/kg, and 55% of those receiving 10 mg/kg. In noncarriers, there were no cases in the 1-mg/kg group. The incidence was 9%, 11%, and 17% in the 3-, 6-, and 10-mg/kg groups of noncarriers respectively. Patients who developed ARIA had the choice of dropping out, opting for a lower dose, or continuing the study at their original dose. Most who developed ARIA (56%) chose to continue treatment.
There were three deaths: two in the placebo group and one in the 10-mg/kg group. None were related to the study drug.
According to Biogen, aducanumab is a fully human IgG1 monoclonal antibody that binds aggregated forms of amyloid, not monomer, and preferentially attaches to parenchymal amyloid rather than vascular amyloid. It was “derived from a deidentified library of B cells collected from healthy elderly subjects with no signs of cognitive impairment and cognitively impaired elderly subjects with unusually slow cognitive decline.”
On Twitter @Alz_Gal
WASHINGTON – An antiamyloid antibody that showed significant cognitive benefit at 10 mg/kg failed to deliver similar good news at a lower dose in the first randomized, antiamyloid antibody trial comprising only patients who screened positive for amyloid-beta plaques on PET imaging.
At 6 mg/kg, aducanumab, a fully human monoclonal antibody, cleared amyloid brain plaques almost as well as the higher dose. But although there were numerical improvements on cognitive measures, these were not statistically significant, Dr. Jeff Sevigny said at the Alzheimer’s Association International Conference 2015.
The drug is being developed by Biogen. Dr. Sevigny is the company’s senior medical director of neurodegenerative disorders.
The PRIME study enrolled 166 patients with prodromal or mild Alzheimer’s who screened positive for amyloid-beta plaques on PET imaging. This ensured a pure cohort of patients with amyloid-beta plaques – something that has been lacking in antiamyloid antibody trials. Some researchers have estimated that up to 15% of those enrolled in previous trials actually had no amyloid-beta in the brain, a finding that could seriously dilute any efficacy signal of a drug designed to remove the protein.
The 52-week phase Ib study randomized patients to placebo or to 1-, 3-, 6-, or 10-mg/kg monthly infusions of aducanumab. In all, patients received 14 infusions. While the trial was designed to evaluate safety and tolerability, it did include preliminary cognitive data in the form of the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB).
The initial study readout was reported in March amid global hoopla. The 3- and 10-mg/kg doses removed amyloid-beta from the brain; the 10-mg/kg dose delivered significant benefits on both cognitive measures. Patients taking the 10-mg/kg dose dipped about half a point below baseline on the MMSE, compared with nearly a 3-point drop for those on placebo. The 3-mg/kg dose also conferred significant benefits against cognitive decline.
Aducanumab was hailed as what could be the “Goldilocks drug” for Alzheimer’s – the first evidence of an antibody that both engaged the amyloid-beta target and provided significant cognitive improvements, although some researchers cautioned against overinterpretation of such early-phase results.
Patients in PRIME had a mean MMSE of 25, and about two-thirds were apolipoprotein E–epsilon 4 (APOE4) positive. Close to half were in the prodromal stage and the remainder had mild Alzheimer’s.
At 52 weeks, patients taking placebo worsened by 2.81 points on the MMSE. Patients taking 6 mg/kg lost 1.96 points – not a significant difference. The 10-mg/kg MMSE results were statistically significant, with a decline of 0.56 in the active group. Even the 3-mg/kg dose performed better than 6 mg/kg, with a decline of 0.70 points – significantly better than the placebo group.
The story was similar on the CDR-SB measure. The placebo group worsened by 1.87 points at week 52, while the 6-mg/kg group worsened by 1.11 points – again not statistically significant. Only the 10-mg/kg dose achieved a statistically significant difference relative to placebo (0.63 points). The 1-mg/kg dose was not significantly better than placebo on either the MMSE or CDR-SB.
All doses except for 1 mg/kg lowered amyloid-beta plaque burden. In the placebo arm, the level of amyloid remained unchanged at both imaging time points (26 and 52 weeks). Plaque moved out in a dose- and time-dependent manner, with 6 and 10 mg/kg removing increasing amounts of the protein.
Amyloid-related imaging abnormalities (ARIA), a brain inflammation related to the removal of amyloid plaques, occurred in 13% of the 3-mg/kg group, 33% of the 6-mg/kg group; and 47% of the 10-mg/kg group. Most of these (89%) occurred in the initial 5 weeks; most (65%) were asymptomatic. The remainder caused mild and transient symptoms, with headache, visual disturbances, and cognitive worsening that resolved by 12 weeks.
APOE4 carriers were particularly subject to ARIA. It occurred in 5% of patients taking the 1-mg/kg and 3-mg/kg doses, 43% of those taking 6 mg/kg, and 55% of those receiving 10 mg/kg. In noncarriers, there were no cases in the 1-mg/kg group. The incidence was 9%, 11%, and 17% in the 3-, 6-, and 10-mg/kg groups of noncarriers respectively. Patients who developed ARIA had the choice of dropping out, opting for a lower dose, or continuing the study at their original dose. Most who developed ARIA (56%) chose to continue treatment.
There were three deaths: two in the placebo group and one in the 10-mg/kg group. None were related to the study drug.
According to Biogen, aducanumab is a fully human IgG1 monoclonal antibody that binds aggregated forms of amyloid, not monomer, and preferentially attaches to parenchymal amyloid rather than vascular amyloid. It was “derived from a deidentified library of B cells collected from healthy elderly subjects with no signs of cognitive impairment and cognitively impaired elderly subjects with unusually slow cognitive decline.”
On Twitter @Alz_Gal
FROM AAIC 2015
Key clinical point: The antiamyloid antibody aducanumab failed to deliver cognitive benefits at 6 mg/kg, throwing some doubt on more positive results from the initial study readout in March.
Major finding: At 52 weeks, patients taking the 6-mg/kg monthly dose worsened by 1.96 points on the MMSE and 1.11 points on the CDR-SB, which were not significantly different from the placebo group’s worsening of 2.81 points and 1.87 points, respectively.
Data source: The trial randomized 166 patients with prodromal or mild Alzheimer’s to 52 weeks of placebo or aducanumab infusions at 1, 3, 6, and 10 mg/kg.
Disclosures: Biogen is developing the molecule and funded the study. Dr. Sevigny is the company’s senior medical director of neurodegenerative disorders.
Estrogen Therapy Linked to Brain Atrophy in Women With Diabetes
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
AT AAIC 2015
Estrogen therapy linked to brain atrophy in women with diabetes
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
On Twitter @Alz_Gal
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
On Twitter @Alz_Gal
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
On Twitter @Alz_Gal
AT AAIC 2015
Key clinical point: Prescribing estrogen therapy for older women with type 2 diabetes could increase the risk of brain atrophy.
Major finding: Older women with type 2 diabetes who took estrogen therapy had about an 18-cc lower total brain volume than women with diabetes who took placebo and than women without the disease.
Data source: WHIMS-MRI was a large parallel-group study that examined the effect of hormone therapy on the brain and cognition in postmenopausal women.
Disclosures: Dr. Hugenschmidt reported having no relevant financial disclosures.
