Table 3.
Population Type | Study Type | Sample Size/Age Range | Type of Measurement | Areas Affected | Evidence for Divergence | Reference |
---|---|---|---|---|---|---|
APOE π4 carriers vs. non-carriers (all w/1st- or 2nd-degree family history of dementia) | Cross-sectional | n= 24; ages 26β45 | Gray matter atrophyGray matter increase | Bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal corticesBilateral cerebellar, middle occipital, bilateral thalamic, bilateral fusiform, right lingual gyri, and some bilateral hippocampal regions | Patterns seen in carriers compared to non-carriers | Alexander et al., 2012β |
Healthy APOE π3 homozygous adults (VL/VL vs. S/S vs. S/VL TOMM40 poly-T lengths) | Cross-sectional | n = 117 (VL/VL = 35, S/S = 38, S/VL = 44); mean age = 55 | Gray matter atrophy | Medial ventral precuneus, ventral posterior cingulate | Dose-dependent effects (greater atrophy per VL allele) | Johnson et al., 2011β |
Late middle-aged adults assessed for family history of parental AD (FH) and APOE π4 genotype | Cross-sectional | n = 343; ages 47β76 | White matter damage | Genu of corpus callosum, superior longitudinal fasciculusUncinate fasciculus | Higher FA in FH+Lower axial diffusivity in FH+, APOE π4-; higher axial diffusivity in FH+, APOE π4+ | Adluru et al., 2014β |
APOE π4/π4 vs. π3/π4 vs. π3/π3 | Cross-sectional | n= 60; ages 49β79 | White matter damage | Posterior corpus callosum, occipito-frontal fasciculus, left hippocampus | Reduced FA in carriers compared to non-carriers (ages 49β64) | Persson et al., 2006β |
APOE π4 carriers vs. non-carriers | Cross-sectional | n = 203; ages 21.1β69.9 (mean = 47.6) | White matter damage | Basal temporal lobe, internal capsule, anterior parts of corpus callosum, forceps minor, superior longitudinal fasciculus, occipital and corticospinal pathways | Increased RD and MD in carriers compared to non-carriers | Westlye et al., 2012β |
Young adult vs. non-demented older adult vs. AD older adult | Cross-sectional | n = 75 (25 young, 25 non-demented older, 25 AD older); mean age young = 22, older = 77, AD older = 77) | White matter damage | Corpus callosum, lobar regions | Age affects in anterior white matter; AD-specific effects in posterior white matter | Head et al., 2004β‘ |
Middle-aged adults assessed for parental family history (FH) of AD and APOE π4 genotype | Cross-sectional | n = 136; mean age FH+/π4+ = 57.5, FH+/π4- = 57.4, FH-/π4+ = 55.4, FH-/π4- = 58.4 | White matter damage | Bilateral anterior corona radiata, left uncinate fasciculus/inferior fronto-occipital fasciculus, left superior corona radiata, left superior longitudinal fasciculus, left tapetum, bilateral posterior corona radiata, parts of the corpus callosum, right posterior cingulum, bilateral hippocampus | Reduced FA in FH+ | Bendlin et al., 2010β |
Non-demented vs. AD late middle-aged adults | Cross-sectional | n = 37; mean age cognitively normal = 61.5, AD = 62.8 | White matter damage | Left anterior cingulum, left posterior cingulum, bilateral descending cingulum, left uncinate tracts | Reduced FA in AD compared to cognitively normal | Zhang et al., 2009β |
Young adult vs. MCI vs. non-demented older adult vs. mild AD | Cross-sectional | n = 372; mean age young = 22.2, MCI = 61.4, non-demented older = 76.7, mild AD = 76.6 | Network-related volume loss | Superior frontal cortices, putamen, caudateHippocampus; entorhinal, retrosplenial, posterior cingulate, precuneus cortices | Age-related changesAD-related changes | Fjell et al., 2010β |
Non-demented vs. AD older adults | Longitudinal | n = 26; mean age non-demented = 71.4, AD = 68.4 | Volume loss | Right hippocampus Left hippocampus | β8.2% Β± 2.6% per year in AD; -0.2 Β± 1.2% per year in controls | Thompson et al., 2004β‘ |
Left hippocampus | β4.9% Β± 1.8% per year in AD; -3.8 Β± 1.6% per year in controls |
APOE π4, Apolipoprotein E π4 allele; TOMM-40, Translocase of the outer mitochondrial membrane poly-T polymorphism; VL, Very long poly-T allele (associated with earlier onset of AD); S, Short poly-T allele; FH, Family history of parental AD, meaning one or both of the individualβs parents has a diagnosis of AD/dementia; FA, Fractional anisotropy; MD, Mean diffusivity; aMCI, Amnestic mild cognitive impairment; RD, Radial diffusivity; βreports on preclinical dementia in midlife; β‘ shows divergence of healthy and pathological aging, one area promising for midlife effects.