Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease

University of Kansas School of Medicine, Department of Neurology, 2100 West 36th Ave., Suite 110, Kansas City, KS 66160, USA.
Neurology (Impact Factor: 8.29). 01/2010; 74(2):113-20. DOI: 10.1212/WNL.0b013e3181c918cb
Source: PubMed


A consistently identified risk factor for Alzheimer disease (AD) is family history of dementia, with maternal transmission significantly more frequent than paternal transmission. A history of maternal AD may be related to AD-like glucose consumption in cognitively healthy subjects. In this cross-sectional study, we tested whether cognitively healthy people with a family history of AD have less gray matter volume (GMV), an endophenotype for late-onset AD, than individuals with no family history, and whether decreases in GMV are different in subjects with a maternal family history.
As part of the Kansas University Brain Aging Project, 67 cognitively intact individuals with a maternal history of late-onset AD (FHm, n = 16), a paternal history of AD (FHp, n = 8), or no parental history of AD (FH-, n = 43), similar in age, gender, education, and Mini-Mental State Examination score, were scanned at 3 T. We used voxel-based morphometry to examine GMV differences between groups, controlling for age, gender, and apoE4.
Cognitively healthy individuals with a family history of late-onset AD had significantly decreased GMV in the precuneus, middle frontal, inferior frontal, and superior frontal gyri compared with FH- individuals. FHm subjects had significantly smaller inferior frontal, middle frontal, precuneus, and lingual gyri compared with FH- and FHp subjects.
Overall, maternal family history of Alzheimer disease (AD) in cognitively normal individuals is associated with lower gray matter volume in AD-vulnerable brain regions. These data complement and extend reports of cerebral metabolic differences in subjects with a maternal family history.

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Available from: Jeffrey M Burns, Apr 09, 2014
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    • "Indeed, unknown genegene and gene-environment interactions are likely to modulate the effect of this genetic factor on brain structure and function, potentially resulting in both overestimation and masking of APOE4 effects (see Donix et al. 2012 for review). In this respect, APOE genotype and family history risk were shown to have independent and/or additive contributions to brain structure (Donix et al. 2010b; Honea et al. 2010, 2011) or metabolism (Mosconi et al. 2007, 2009). "
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    • "This trend is consistent with recent reports (Mosconi et al., 2010, 2013) in which greater amyloid burden in healthy older adults with maternal FH was described. This is also consistent with reports in which it was suggested that maternal FH is associated with lower cerebral blood flow (Okonkwo et al., 2012b), lower metabolic rate of glucose (Mosconi et al., 2007, 2009), cerebral atrophy (Honea et al., 2010, 2011), and altered white matter microstructure on diffusion tensor imaging scans (Bendlin et al., 2010). Maternal inheritance of AD is significantly more common than paternal inheritance (Edland et al., 1996). "
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    • "Studies assessing the effect of APOE4 on brain structure using structural MRI are numerous but lead to diverging findings. Thus, several studies have reported a significant atrophy (or cortical thinning) in APOE4 carriers compared to non carriers, most often in brain regions most susceptible to AD, i.e. medial temporal structures (hippocampus, entorhinal cortex, etc; Plassman et al., 1997; Tohgi et al., 1997; Lemaître et al., 2005; Lind et al., 2006; Wishart et al., 2006; Burggren et al., 2008; Honea et al., 2009; Suthana et al., 2010; O'Dwyer et al., 2012). Other regions are also reported such as the lateral temporal and prefrontal cortex (Wishart et al., 2006) or parietal areas (Honea et al., 2009). "
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