Men and women with Alzheimer’s disease have different types of gray matter damage, according to a study presented at the 98th Annual Meeting of the Radiological Society of North America. Cognitive decline occurs earlier in women, while men experience more rapid cognitive decline. Women experience brain atrophy earlier than men, but their cognitive decline is not as rapid, said Maria Vittoria Spampinato, PhD, of the University of South Carolina School of Medicine in Charleston. Men’s and women’s brains respond differently to the pathology of Alzheimer’s disease,” she said. The men and women in this study were clinically at the same point in the disease. However, we found that men had dramatic brain volume with cognitive decline. Women, on the other hand, already experienced a decline in brain volume much earlier in the course of cognitive decline.” Previously, in studying the differences between brain atrophy in patients with mild cognitive impairment and those with Alzheimer’s disease with or without language impairment, Dr. Spampinato noted that language impairment tended to occur more severely in women than in men. Women also had an increased risk of Alzheimer’s disease, she said. So, based on the prior findings, she and her research team analyzed data from 60 men and 49 women from the Alzheimer’s Disease Neurological Impact Initiative (ADNI) study, a multicenter study conducted in the United States and Canada to examine the transition from normal old age to mild cognitive impairment and Alzheimer’s disease. The mean age of the study’s subjects was 77 years (70-84 years), and all of these patients progressed from amnestic mild cognitive impairment to Alzheimer’s disease during the ADNI study. The researchers obtained magnetic resonance images of the brain 12 months before the diagnosis of Alzheimer’s disease, at the time of diagnosis and 12 months after the diagnosis. They also performed cortical volume mapping and collected data on race, right- and left-handed habits, years of education, genetic risk factors, cognitive ability tests and cerebrospinal fluid. The findings found progressive cognitive decline in both men and women (p<0.001) and a significant interaction between Clinical Composite Dementia Scale (CDR-SB) scores and gender (p = 0.035). At the time of diagnosis of Alzheimer's disease, men had worse CDR-SB scores compared to women. Cortical volume maps showed that women had more severe atrophy in the anterior cingulate gyrus at 12 months prior to AD diagnosis and in the bilateral middle temporal gyrus, bilateral cingulate gyrus, left inferior callosal gyrus, and right insula at the time of AD diagnosis compared to men. Differences remained between men and women 12 months after the diagnosis of Alzheimer's disease. In women, gray matter volume loss was more severe in the left hippocampus, bilateral temporal lobes, and right parietal lobe; in men, gray matter volume loss was more severe in the bilateral hippocampus, right parahippocampal gyrus, left insula, left caudate nucleus, left frontal lobe, and left parietal lobe. Dr. Spampinato explained that "women experience brain atrophy at a relatively early stage of cognitive decline compared to men, but these differences eventually disappear because more brain volume loss occurs in men as they progress from mild cognitive impairment to Alzheimer's disease." She added that it is important to study the preclinical staging of the disease during the progression from normal aging to mild cognitive impairment to help determine if the male and female brains respond differently to treatment. "These differences also have implications for mild cognitive impairment and Alzheimer's disease treatment progression," Dr. Spampinato noted. These factors need to be taken into account when testing new drugs in clinical trials. Understanding the differences between the types of brain atrophy in men and women will help researchers better determine how patients respond to treatment with drugs, she said. Commenting on this, Dr. David M. Hovsepian, professor of radiology at Stanford University Medical Center in California, said it is not clear why there are significant gender differences in Alzheimer's disease. Understanding these differences will help guide future clinical research, he said. Jeffrey R. Petrella, MD, PhD, director of the Alzheimer's Disease Imaging Research Laboratory at Duke University Medical Center in North Carolina, said a unique aspect of the study is that it focused on patients with prodromal Alzheimer's disease. He said, "Women appeared to have more severe atrophy before and at the time of diagnosis, but men had worse cognitive impairment. This suggests that women have higher cognitive reserve compared to men, which may make them more resistant and, therefore, less symptomatic."