Smith, Glenn E.

AbstractBackgroundGenetic variants at the CLU, CR1, and PICALM loci associate with risk for late‐onset Alzheimer's disease (LOAD) in genomewide association studies. In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in black and white subjects.MethodsWe pursued an association study between single nucleotide polymorphism genotypes at the CLU, CR1, and PICALM loci and memory endophenotypes. We assessed black subjects (AA series: 44 with LOAD and 224 control subjects) recruited at Mayo Clinic Florida and whites recruited at Mayo Clinic Minnesota (RS series: 372 with LOAD and 1690 control subjects) and Florida (JS series: 60 with LOAD and 529 control subjects). Single nucleotide polymorphisms at the LOAD risk loci CLU (rs11136000), CR1 (rs6656401, rs3818361), and PICALM (rs3851179) were genotyped and tested for association with Logical Memory immediate recall, Logical Memory delayed recall, Logical Memory percent retention, Visual Reproduction immediate recall, Visual Reproduction delayed recall, and Visual Reproduction percent retention scores from the Wechsler Memory Scale–Revised using multivariable linear regression analysis, adjusting for age at exam, sex, education, and apolipoprotein E ε4 dosage.ResultsWe identified nominally significant or suggestive associations between the LOAD‐risky CR1 variants and worse Logical Memory immediate recall scores in blacks (P = .068–.046, β = −2.7 to −1.2). The LOAD‐protective CLU variant is associated with better logical memory endophenotypes in white subjects (P = .099–.027, β = 0.31–0.93). The CR1 associations persisted when the control subjects from the AA series were assessed separately. The CLU associations appeared to be driven by one of the white series (RS) and were also observed when the control subset from RS was analyzed.ConclusionThese results suggest for the first time that LOAD risk variants at CR1 may influence memory endophenotypes in blacks. In addition, the CLU LOAD‐protective variant may confer enhanced memory in whites. Although these results would not remain significant after stringent corrections for multiple testing, they need to be considered in the context of the LOAD associations with which they have biological consistency. They also provide estimates for effect sizes on memory endophenotypes that could guide future studies. The detection of memory effects for these variants in clinically normal subjects, implies that these LOAD risk loci might modify memory prior to clinical diagnosis of AD.

Objective Individuals with amnestic mild cognitive impairment (MCI) have few empirically based treatment options for combating their memory loss. This study sought to examine the efficacy of a calendar/notebook rehabilitation intervention, the memory support system (MSS), for individuals with amnestic MCI. Methods Forty individuals with single domain amnestic MCI and their program partners were randomized to receive the MSS, either with training or without (controls). Measures of adherence, activities of daily living, and emotional impact were completed at the first and last intervention sessions and again at 8 weeks and 6 months post intervention. Results Training in use of a notebook/calendar system significantly improved adherence over those who received the calendars but no training. Functional ability and memory self‐efficacy significantly improved for those who received MSS training. Change in functional ability remained significantly better in the intervention group than in the control group out to 8‐week follow‐up. Care partners in the intervention group demonstrated improved mood by 8‐week and 6‐month follow‐ups, whereas control care partners reported worse caregiver burden by 6‐month follow‐up. Conclusions Memory support system training resulted in improvement in activities of daily living and sense of memory self‐efficacy for individuals with MCI. Although activities of daily living benefits were maintained out to 8 weeks post intervention, future inclusion of booster sessions may help extend the therapeutic effect out even further. Improved mood of care partners of trained individuals and worsening sense of caregiver burden over time for partners of untrained individuals further support the efficacy of the MSS for MCI. Copyright © 2012 John Wiley & Sons, Ltd.