4 March 2011. Beyond age, the next biggest risk factor for late-onset Alzheimer’s disease is having the disorder in one’s pedigree, especially on Mom’s side. Neuroimaging studies have supported this observation, revealing more preclinical AD-like brain changes in healthy seniors with a maternal history of AD, compared to those with a paternal or negative history. In this month’s Neurology, first author Robyn Honea and colleagues at the University of Kansas School of Medicine, Kansas City, extend this line of evidence with two-year longitudinal data showing faster regional brain atrophy in adult children of mothers with AD. The finding was enough to catch the attention of The New York Times.
When monitored using positron emission tomography (PET), cognitively intact elderly with a maternal history of AD show ominous brain features—among them, decreased glucose metabolism (ARF related news story and Mosconi et al., 2007; Mosconi et al., 2009) and greater amyloid load (ARF related news story on Mosconi et al., 2010). On magnetic resonance imaging (MRI), these folks also have reduced gray matter volume, according to a recent study by Honea and colleagues (Honea et al., 2010; see also Berti et al., 2011). The current paper is a longitudinal extension of that cross-sectional MRI study, with brain atrophy rates determined two years after baseline.
In the cross-sectional study, Honea and colleagues analyzed structural MRI data on 67 cognitively intact seniors enrolled in the University of Kansas’ Brain Aging Project. Compared to participants with a paternal history, or no family history, of Alzheimer’s disease, the group with AD mothers showed lower gray matter volume in AD-vulnerable brain regions. Now, with two-year follow-up MRI data on 53 subjects (32 with no family history, 10 with paternal history, and 11 with maternal history of AD), the present study suggests that people with AD mothers also have accelerated brain atrophy in disease-affected regions. The researchers found strongest evidence of decay in the precuneus and parahippocampal gyrus, areas that overlap with those showing high fibrillar Aβ burden (Mosconi et al., 2010).
The new findings are important for a number of reasons, noted Lisa Mosconi, New York University School of Medicine, New York, in an e-mail to ARF. Brain atrophy rates have been linked to future decline from normal cognition to AD (see ARF related news story), and MRI is widely available for clinical practice as well as clinical trials, she wrote. “Together with previous studies, these new findings strengthen the hypothesis of a genetic component to the biomarker abnormalities in this group of at-risk individuals [i.e., seniors with a maternal history of AD],” wrote Mosconi (see full comment below).
The authors speculate that the “genetic component” may lie within mitochondrial DNA, considering its exclusively maternal transmission and growing evidence for the role of mitochondrial dysfunction in AD (see Reddy and Beal, 2008). Indeed, mitochondrial DNA “may very well be associated with the imaging findings,” Mosconi noted. She added that larger, longer studies will need to follow people with AD mothers “until some of them actually develop AD, in order to determine the prediction accuracy and absolute risk of MRI-determined atrophy and other biomarkers for AD.” Honea expressed similar views in the New York Times article on the current study, noting that more research is needed to achieve the goal of using diagnostic brain scans to identify high-risk individuals before they deteriorate.—Esther Landhuis.
Honea RA, Swerdlow RH, Vidoni ED, Burns JM. Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease. Neurology. 1 March 2011;76:822-829. Abstract