Brain Atrophy in Cognitively Normal Adults Whose Mothers had Alzheimer’s Disease

Besides age, having a family history of Alzheimer’s disease (AD) is the most significant risk factor for AD. Researchers wanted to determine if brain atrophy was present in people who are not experiencing symptoms of AD, but have a family history of the disease.1

Individuals with a family history of AD, but who were cognitively normal themselves, had significantly increased whole-brain gray brain matter atrophy and CSF expansion when compared to cognitively normal individuals with no family history of AD. When the family history group was evaluated further, specifically those with a family history of maternal AD had the significant brain matter atrophy.  Individuals with the e4 version of the apolipoprotein allele (APOE-e4)  had more regional atrophy in the frontal cortex of their brains than non APOE-e4  carriers. Overall, individuals who did not themselves have dementia, but who had a maternal family history of AD, had progressive gray matter volume reductions in select AD-vulnerable brain regions. This data complements other research that individuals with a maternal family history of AD are at greater risk for developing AD themselves.

The participants in this project were individuals aged 60 and over who were enrolled in the University of Kansas Brain Aging Project. All participants were evaluated with a medical history questionnaire, a physical examination, laboratory tests, and neuropsychological and MRI examinations at baseline and at 24 months. They all were evaluated by a board-certified neurologist to determine their Clinical Dementia Rating (CDR), and only individuals with a CDR of 0 were included in this study, as the researchers wanted to focus on people who were not experiencing any symptoms of cognitive decline. All study participants had a family history of at least one first-degree relative with dementia that began between the ages of 60 and 80. However, if both of their parents had AD, the individual was excluded from the study. The participants were then divided into study groups of maternal family history of AD or paternal family history of AD, and compared with individuals with no parental history of AD.

The prevalence of individuals that were APOE-e4 carriers was significantly greater for those with a maternal family history of AD (63%) compared to those with a paternal family history of AD (20%) and no family history of AD (15%). Individuals with a family history of AD (either maternal or paternal) had significantly more whole brain atrophy (gray matter and white matter) compared to individuals with no family history of AD. Individuals with the APOE-e4 allele had progressive atrophy primarily in the frontal cortices of the brain, specifically in the left inferior frontal cortex and the left superior frontal cortex. These regional atrophy changes did not statistically overlap with the maternal family history regional atrophy changes in the precuneus and parahippocampal gyrus. Independent of APOE-e4 status, age, and gender, individuals with a maternal family history had greater atrophy in two regions than those with no family history of AD or those with a paternal family history of AD. This data complements other research that individuals with a maternal family history of AD are at greater risk for developing AD themselves.

  1. Honea RA, Swerdlow RH, Vidoni ED, Burns JM. Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease. Neurology. March 2011. 76: 822-829.

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