Fran Lowry

November 27, 2012

CHICAGO — Alzheimer's disease produces a different pattern of gray matter loss in men and women, according to a study presented here at the Radiological Society of North America 98th Scientific Assembly and Annual Meeting.

Brain atrophy begins sooner in women than in men, but their cognitive decline is less rapid, said Maria Vittoria Spampinato, MD, from the Medical University of South Carolina in Charleston. "Male and female brains respond differently to Alzheimer's disease pathology," she told Medscape Medical News.

Dr. Maria Vittoria Spampinato

"The men and women in this study were very similar clinically and were at the same stage of disease. However, in the men, we found a steep brain volume loss at the time of cognitive decline, whereas in the women, volume loss occurred at an earlier stage of cognitive deterioration," she said.

In studying differences in brain atrophy between subjects with mild cognitive impairment and Alzheimer's disease with and without language impairment, Dr. Spampinato noticed that women tend to have worse language impairment than men.

Women also have an increased risk of developing Alzheimer's disease, she said.

She and her team analyzed data on 60 men and 49 women from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multi-institutional study conducted in the United States and Canada to examine the transition from normal aging to mild cognitive impairment to Alzheimer's disease.

The mean age of the study subjects was 77 years (range, 70 - 84). They progressed from amnestic mild cognitive impairment to Alzheimer's disease during their participation in the ADNI.

The researchers obtained magnetic resonance images of the brains 12 months before the diagnosis of Alzheimer's disease, at the time of diagnosis, and 12 months after the diagnosis.

They also generated gray matter volume maps and collected data on ethnicity, handedness, years of education, genetic risk factors, cognitive tests, and cerebrospinal fluid.

There was progressive cognitive decline in both men and women (P < .001), with significant interaction between Clinical Dementia Rating Sum of the Boxes (CDR-SB) score (a measure of cognitive status) and sex (P = .035). At the time of Alzheimer's disease diagnosis, CDR-SB scores were worse in men than in women.

Gray matter volume maps showed greater atrophy in women than in men in the posterior cingulate gyrus at 12 months before diagnosis, and in the bilateral middle temporal gyrus, bilateral cingulate gyrus, left subcallosal gyrus, and right insula at the time of diagnosis.

There were no significant differences in gray matter volume between men and women at either of these time points, Dr. Spampinato reported.

However, women lost volume in the bilateral uncus and men lost volume in the bilateral inferior frontal lobe and right uncus in the 12 months before their diagnosis.

A difference was also seen during the 12 months after being diagnosed with Alzheimer's disease. In women, loss of gray matter volume was greater in the left hippocampus, bilateral temporal lobe, and right parietal lobe; in men, loss of gray matter volume was greater in the bilateral hippocampus, right parahippocampal gyrus, left insula, and in the left caudate, left frontal, and left parietal lobes.

"Atrophy develops at an earlier stage of cognitive deterioration in women than in men, but these differences eventually disappear because greater brain volume loss occurs in men during the progression from mild cognitive impairment to Alzheimer's disease," Dr. Spampinato explained.

It will be important to investigate the preclinical stages of disease during the transition from normal aging to mild cognitive impairment to determine whether male and female brains respond differently to treatment, she added.

"These differences also have implications for the development of therapies for mild cognitive impairment and Alzheimer's disease," Dr. Spampinato noted. "They should be taken into account when testing new drugs in clinical trials. Knowing the difference between male and female patterns of atrophy will help researchers better determine a patient's response to drug therapy," she said.

Dr. David Hovsepian

David M. Hovsepian, MD, professor of radiology at Stanford University Medical Center in California, who commented on this study for Medscape Medical News, said there are clearly sex differences in Alzheimer's disease that are not understood.

"This is a fascinating early peek at where some of these differences may lie and how they may have some relevance in predicting the way Alzheimer's progresses in men and women," Dr. Hovsepian said.

He agrees that being aware of these differences will help guide future clinical studies.

"Now that we have something measurable, and as we look at new therapies, we are clearly going to want to see whether there are gender differences. This is a tool that is going to show us something very revealing about who might benefit from certain therapies and who might not."

Jeffrey R. Petrella, MD, director of the Alzheimer Disease Imaging Research Lab at the Duke University Medical Center in Durham, North Carolina, told Medscape Medical News that a unique aspect of this study is that it focuses on prodromal Alzheimer's disease patients.

"Women seemed to have greater atrophy before and at the time of diagnosis, yet men were worse off cognitively," Dr. Petrella said.

"This suggests that higher cognitive reserve in women may render them more resistant, and therefore less symptomatic, for a given disease burden, compared with men. Cognitive reserve is enhanced by higher levels of mental, physical, and social engagement in everyday life," he noted.

Dr. Spampinato, Dr. Hovsepian, and Dr. Petrella have disclosed no relevant financial relationships.

Radiological Society of North America (RSNA) 98th Scientific Assembly and Annual Meeting: Abstract SSE16-02. Presented November 26, 2012.