White Matter Lesions May Affect Alzheimer's Tx

ATLANTA – Fast fluid-attenuated inversion-recovery MR images reveal that the brains of patients with Alzheimer's disease show more extensive areas of focal white matter hyperintensities than do those of normal controls, and the extent of pathology is inversely correlated with cognitive performance, said Michael D. Devous, Ph.D., of the University of Texas Southwestern Medical Center at Dallas.

This new evidence strengthens the link between Alzheimer's disease and cerebrovascular pathology, he said in a poster presentation at the annual meeting of the Society for Neuroscience.

The white matter hyperintensities, also known as leukoaraiosis, are thought to be a consequence of cerebral small vessel disease.

By calculating the ratio of the volume of the white matter hyperintensities to whole brain volume (the leukoaraiosis index), physicians may be able to identify Alzheimer's patients at higher risk of rapid progression or those who are unlikely to respond well to treatment, Mitali Bose, a graduate student at the University of Texas at Dallas and a coauthor, said in an interview.

The mean leukoaraiosis index was almost twice as high in the Alzheimer's group (n = 30) than in the normal control group (n = 40) (1 ± 0.9 vs. 0.6 ± 0.7, P = .01). Total leukoaraiosis volume was also significantly higher in the Alzheimer's group than in controls (14 ± 11 vs. 6 ± 9, P = .01) while whole brain volume was significantly lower in patients than in controls (1,100 ± 107 vs. 1,164 ± 112, P =.01).

Alzheimer's patients with higher leukoaraiosis index scores were more likely to have poorer cognition, as measured with the Mini Mental State Examination (r = −0.28, P less than .05). “While this correlation was modest, it suggests an impact of leukoaraiosis on a coarse measure of general cognitive status. It is possible that correlating the specific neuroanatomical sites of leukoaraiosis with a more refined neuropsychological variable may provide additional insight into the effect of this abnormality on patient cognition,” said Dr. Devous, director of the Neuroimaging Core of the Alzheimer's Disease Center, UT Southwestern Medical Center.

The researchers also compared leukoaraiosis index scores to creatinine levels, another marker of vascular risk, and found a significant positive correlation between the two indicators (r = 0.35, P less than .01). “We still don't know the exact pathology underlying leukoaraiosis as seen on FLAIR MRI, but if [ongoing work finds that] there is correlation with pathological findings on postmortem brain, it may help us relate the leukoaraiosis to other vascular risk factors. Of course, a main goal of this work is to understand this and other risk factors as predictors of symptom severity, disease progression, and response to therapy,” Dr. Devous said in an interview.

“This is semiautomated software so it is at the first level of application. It should have clinical application once the tool is totally automated,” said Ms. Bose. The group is now exploring whether hyperintensities in the periventricular or deep subcortical areas have differential prognostic value.

'We still don't know the exact pathology underlying leukoaraiosis as seen on' MRI. DR. DEVOUS

Subcortical and periventricular areas of hyperintensities are seen in this fluid-attentuated inversion-recovery MR image. Courtesy Dr. Michael D. Devous

ATLANTA – Fast fluid-attenuated inversion-recovery MR images reveal that the brains of patients with Alzheimer's disease show more extensive areas of focal white matter hyperintensities than do those of normal controls, and the extent of pathology is inversely correlated with cognitive performance, said Michael D. Devous, Ph.D., of the University of Texas Southwestern Medical Center at Dallas.

This new evidence strengthens the link between Alzheimer's disease and cerebrovascular pathology, he said in a poster presentation at the annual meeting of the Society for Neuroscience.

The white matter hyperintensities, also known as leukoaraiosis, are thought to be a consequence of cerebral small vessel disease.

By calculating the ratio of the volume of the white matter hyperintensities to whole brain volume (the leukoaraiosis index), physicians may be able to identify Alzheimer's patients at higher risk of rapid progression or those who are unlikely to respond well to treatment, Mitali Bose, a graduate student at the University of Texas at Dallas and a coauthor, said in an interview.

The mean leukoaraiosis index was almost twice as high in the Alzheimer's group (n = 30) than in the normal control group (n = 40) (1 ± 0.9 vs. 0.6 ± 0.7, P = .01). Total leukoaraiosis volume was also significantly higher in the Alzheimer's group than in controls (14 ± 11 vs. 6 ± 9, P = .01) while whole brain volume was significantly lower in patients than in controls (1,100 ± 107 vs. 1,164 ± 112, P =.01).

Alzheimer's patients with higher leukoaraiosis index scores were more likely to have poorer cognition, as measured with the Mini Mental State Examination (r = −0.28, P less than .05). “While this correlation was modest, it suggests an impact of leukoaraiosis on a coarse measure of general cognitive status. It is possible that correlating the specific neuroanatomical sites of leukoaraiosis with a more refined neuropsychological variable may provide additional insight into the effect of this abnormality on patient cognition,” said Dr. Devous, director of the Neuroimaging Core of the Alzheimer's Disease Center, UT Southwestern Medical Center.

The researchers also compared leukoaraiosis index scores to creatinine levels, another marker of vascular risk, and found a significant positive correlation between the two indicators (r = 0.35, P less than .01). “We still don't know the exact pathology underlying leukoaraiosis as seen on FLAIR MRI, but if [ongoing work finds that] there is correlation with pathological findings on postmortem brain, it may help us relate the leukoaraiosis to other vascular risk factors. Of course, a main goal of this work is to understand this and other risk factors as predictors of symptom severity, disease progression, and response to therapy,” Dr. Devous said in an interview.

“This is semiautomated software so it is at the first level of application. It should have clinical application once the tool is totally automated,” said Ms. Bose. The group is now exploring whether hyperintensities in the periventricular or deep subcortical areas have differential prognostic value.

'We still don't know the exact pathology underlying leukoaraiosis as seen on' MRI. DR. DEVOUS

Subcortical and periventricular areas of hyperintensities are seen in this fluid-attentuated inversion-recovery MR image. Courtesy Dr. Michael D. Devous

ATLANTA – Fast fluid-attenuated inversion-recovery MR images reveal that the brains of patients with Alzheimer's disease show more extensive areas of focal white matter hyperintensities than do those of normal controls, and the extent of pathology is inversely correlated with cognitive performance, said Michael D. Devous, Ph.D., of the University of Texas Southwestern Medical Center at Dallas.

This new evidence strengthens the link between Alzheimer's disease and cerebrovascular pathology, he said in a poster presentation at the annual meeting of the Society for Neuroscience.

The white matter hyperintensities, also known as leukoaraiosis, are thought to be a consequence of cerebral small vessel disease.

By calculating the ratio of the volume of the white matter hyperintensities to whole brain volume (the leukoaraiosis index), physicians may be able to identify Alzheimer's patients at higher risk of rapid progression or those who are unlikely to respond well to treatment, Mitali Bose, a graduate student at the University of Texas at Dallas and a coauthor, said in an interview.

The mean leukoaraiosis index was almost twice as high in the Alzheimer's group (n = 30) than in the normal control group (n = 40) (1 ± 0.9 vs. 0.6 ± 0.7, P = .01). Total leukoaraiosis volume was also significantly higher in the Alzheimer's group than in controls (14 ± 11 vs. 6 ± 9, P = .01) while whole brain volume was significantly lower in patients than in controls (1,100 ± 107 vs. 1,164 ± 112, P =.01).

Alzheimer's patients with higher leukoaraiosis index scores were more likely to have poorer cognition, as measured with the Mini Mental State Examination (r = −0.28, P less than .05). “While this correlation was modest, it suggests an impact of leukoaraiosis on a coarse measure of general cognitive status. It is possible that correlating the specific neuroanatomical sites of leukoaraiosis with a more refined neuropsychological variable may provide additional insight into the effect of this abnormality on patient cognition,” said Dr. Devous, director of the Neuroimaging Core of the Alzheimer's Disease Center, UT Southwestern Medical Center.

The researchers also compared leukoaraiosis index scores to creatinine levels, another marker of vascular risk, and found a significant positive correlation between the two indicators (r = 0.35, P less than .01). “We still don't know the exact pathology underlying leukoaraiosis as seen on FLAIR MRI, but if [ongoing work finds that] there is correlation with pathological findings on postmortem brain, it may help us relate the leukoaraiosis to other vascular risk factors. Of course, a main goal of this work is to understand this and other risk factors as predictors of symptom severity, disease progression, and response to therapy,” Dr. Devous said in an interview.

“This is semiautomated software so it is at the first level of application. It should have clinical application once the tool is totally automated,” said Ms. Bose. The group is now exploring whether hyperintensities in the periventricular or deep subcortical areas have differential prognostic value.

'We still don't know the exact pathology underlying leukoaraiosis as seen on' MRI. DR. DEVOUS

Subcortical and periventricular areas of hyperintensities are seen in this fluid-attentuated inversion-recovery MR image. Courtesy Dr. Michael D. Devous