Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers

Abstract

Purpose:To investigate the possible effect of the APOE ε4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy ε4 allele carriers compared with noncarriers. Materials and Methods:A total of 211 subjects, ages 27 to 83 years, 51 ε4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE ε4 gene on the gray matter. Results:We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE ε4 carriers compared withthe noncarriers particularly in the prefrontal region (P ϭ 0.02). No gray matter differences were observed between the two groups.Conclusion: APOE ε4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE ε4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.

Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline

“…In addition to our own studies that have reported evidence of increased hippocampal activation in the earliest stages of MCI, relative to normal controls, 2,3,20,21 several other groups have reported hyperactivation in MCI, in particular for successful memory formation. 8,9,22 This paradoxical increase in activation has also been observed in carriers of the APOE ⑀4 allele, 11,12 even among young carriers, 13 and in asymptomatic offspring of individuals with confirmed familial late-onset AD. 23 We did not observe a significant effect of APOE carrier status in this study, perhaps because of the more advanced age of our subjects.…”

“…10 Increased MTL activation has also been reported in asymptomatic individuals at genetic risk. [11][12][13] We hypothesize that hyperactivation might represent an early response to AD pathology, which may predict impending hippocampal failure and memory decline. Longitudinal fMRI research is needed to determine the evolution of fMRI activity over the course of clinical decline.…”

White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

“…Brain imaging studies show reduced white matter volume in AD (Balthazar et al, 2009; Baxter et al, 2006; Chaim et al, 2007; Im et al, 2008; Li et al, 2008; Salat et al, 2009; Stout et al, 1996; Teipel et al, 1998, 2002; Vermersch et al, 1994; Wang et al, 2006), white matter atrophy over time (Hua et al, 2010) and microstructural alterations as indexed by diffusion tensor imaging (DTI) (Bozzali et al, 2002; Canu et al, 2009; Duan et al, 2006; Fellgiebel et al, 2008; Hanyu et al, 1999; Huang et al, 2007, 2012; Medina et al, 2006; Rose et al, 2008; Salat et al, 2010; Stahl et al, 2007; Takahashi et al, 2002; Wang et al, 2012; Xie et al, 2006). Brain changes in AD occur several years before memory symptoms appear, and accordingly, risk factors for AD are also associated with white matter changes, including apolipoprotein E e4 genotype (APOE4) (Bartzokis et al, 2006; Bartzokis et al, 2007; Filippini et al, 2009; Heise et al, 2011; Honea et al, 2009; Nierenberg et al, 2005; Persson et al, 2006; Ryan et al, 2011; Westlye et al, 2012) and parental family history of AD (Bendlin et al, 2010; Xiong et al, 2011). …”

Cued Recall Measure Predicts the Progression of Gray Matter Atrophy in Patients with Amnesic Mild Cognitive Impairment

“…As the Apo E4 genotype is considered to be the main biological risk factor for sporadic AD, this adds evidence supporting the hypothesis that MTLA-MCI patients are at higher risk to suffer from AD pathological changes than SCFA-MCI [36]. The higher frequency of the Apo E4 allele in MTLA-MCI patients may reflect anatomically specific effects of Apo E4 on cortical vulnerability of the MTL [37,38,39,40]. By contrast, the frequency of the Apo4 allele in SCFA-MCI patients was close to that observed in the general population [41].…”