The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer’s dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer’s disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers.

Background Previous neuroimaging studies of recently detoxified alcohol-dependent patients (RDA) have found significant loss of white matter integrity associated with the shrinkage of the frontal lobes and thinning of the corpus callosum, especially the genu. The current study hypothesized that, in addition to exhibiting the most microstructural white matter disruption in RDA, the genu will also evidence the most recovery after abstinence. This microstructural recovery will be associated with improvements in executive functioning measures. Methods Fifteen RDA were examined approximately 2 weeks after abstinence and again after 1 year of abstinence and compared to 15 age- and education-matched nonalcoholic controls using diffusion tensor imaging (DTI). The effects of group, time, and their interactions on fractional anisotropy, radial diffusivity, and axial diffusivity were evaluated with repeated measures MANOVA; in addition, 2 × 2 ANOVA was used to test changes in measures of executive functioning in the 2 groups. Results At 2 weeks of abstinence, DTI of RDA showed significantly lower fractional anisotropy and greater radial diffusivity compared to controls in the genu and body of the corpus callosum. Reexamination after 1 year showed significant time by group interaction with fractional anisotropy increasing and radial diffusivity decreasing in RDA but not controls in these 2 regions. A smaller relapsed group did not show improvements between the 2 time points. Abstinent RDA also showed improvement on Digit Span Backward, a measure of working memory, but did not benefit from practice effects on the Halstead Category Test compared to controls. Conclusions The results suggest susceptibility of the genu and body of the corpus callosum to the effects of alcohol, and the potential for recovery of both these regions after abstinence, perhaps via mechanisms involving myelin reconstitution.

Introduction: Plasma glial fibrillary acidic protein (GFAP) may be associated with amyloid burden, neurodegeneration, and stroke but its specificity for Alzheimer's disease (AD) in the general population is unclear. We examined associations of plasma GFAP with amyloid and tau positron emission tomography (PET), cortical thickness, white matter hyperintensities (WMH), and cerebral microbleeds (CMBs). Methods: The study included 200 individuals from the Mayo Clinic Study of Aging who underwent amyloid and tau PET and magnetic resonance imaging and had plasma GFAP concurrently assayed; multiple linear regression and hurdle model analyses were used to investigate associations controlling for age and sex. Results: GFAP was associated with amyloid and tau PET in multivariable models. After adjusting for amyloid, the association with tau PET was no longer significant. GFAP was associated with cortical thickness, WMH, and lobar CMBs only among those who were amyloid‐positive. Discussion: This cross‐sectional analysis demonstrates the utility of GFAP as a plasma biomarker for AD‐related pathologies.