A systematic review to examine the efficacy of computer-based cognitive interventions for cognitively healthy older adults was conducted. Studies were included if they met the following criteria: average sample age of at least 55 years at time of training; participants did not have Alzheimer’s disease or mild cognitive impairment; and the study measured cognitive outcomes as a result of training. Theoretical articles, review articles, and book chapters that did not include original data were excluded. We identified 151 studies published between 1984 and 2011, of which 38 met inclusion criteria and were further classified into three groups by the type of computerized program used: classic cognitive training tasks, neuropsychological software, and video games. Reported pre-post training effect sizes for intervention groups ranged from 0.06 to 6.32 for classic cognitive training interventions, 0.19 to 7.14 for neuropsychological software interventions, and 0.09 to 1.70 for video game interventions. Most studies reported older adults did not need to be technologically savvy in order to successfully complete or benefit from training. Overall, findings are comparable or better than those from reviews of more traditional, paper-and-pencil cognitive training approaches suggesting that computerized training is an effective, less labor intensive alternative.

Introduction: Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific role for the gut-brain axis in neurodegeneration. Bile acids (BA), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer disease (AD). Methods: Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1,464 subjects including 370 cognitively normal older adults (CN), 284 with early mild cognitive impairment (MCI), 505 with late MCI, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for cofounders and multiple testing. Results: In AD compared to CN, we observed significantly lower serum concentrations of a primary BA (cholic acid CA) and increased levels of the bacterially produced, secondary BA, deoxycholic acid (DCA), and its glycine and taurine conjugated forms. An increased ratio of DCA:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response related genes implicated in AD showed associations with BA profiles. Conclusion: We report for the first time an association between altered BA profile, genetic variants implicated in AD and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut liver brain axis in the pathogenesis of AD.

Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large metabolic differences. We systematically investigated group-specific metabolic alterations by conducting stratified association analyses of 139 serum metabolites in 1,517 individuals from the AD Neuroimaging Initiative with AD biomarkers. We observed substantial sex differences in effects of 15 metabolites with partially overlapping differences for APOE ε4 status groups. Several group-specific metabolic alterations were not observed in unstratified analyses using sex and APOE ε4 as covariates. Combined stratification revealed further subgroup-specific metabolic effects limited to APOE ε4+ females. The observed metabolic alterations suggest that females experience greater impairment of mitochondrial energy production than males. Dissecting metabolic heterogeneity in AD pathogenesis can therefore enable grading the biomedical relevance for specific pathways within specific subgroups, guiding the way to personalized medicine.

Key Points Question Are liver function markers associated with cognition and the “A/T/N” (amyloid, tau, and neurodegeneration) biomarkers for Alzheimer disease? Findings In this cohort study of 1581 older adults, elevated aspartate aminotransferase to alanine aminotransferase ratios were associated with diagnosis of Alzheimer disease, poor cognition, lower cerebrospinal fluid levels of amyloid-β 1-42, increased amyloid-β deposition, higher cerebrospinal fluid levels of phosphorylated tau and total tau, and reduced brain glucose metabolism. Lower levels of alanine aminotransferase were associated with increased amyloid-β deposition, reduced brain glucose metabolism, greater brain atrophy, diagnosis of Alzheimer disease, and poor cognition. Meaning Consistent associations of serum-based liver function markers with Alzheimer disease biomarkers highlight the involvement of metabolic disturbances in the pathophysiology of Alzheimer disease.