Locke, Dona E.C.

Background/Objectives Behavioral problems in individuals with Alzheimer's disease ( AD ) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment ( MCI ). Design Longitudinal observational cohort study. Setting Academic medical center. Participants Members of an apolipoprotein E ( APOE ) ɛ4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory—Revised ( NEO ‐ PI ‐R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO ‐ PI ‐R administrations. Intervention Longitudinal administration of the NEO ‐ PI ‐R and neuropsychological test battery. Measurements Change in NEO ‐ PI ‐R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow‐up duration in nontransitioners. Results NEO ‐ PI ‐R neuroticism T‐scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval ( CI ) = 0.9–4.9 vs 0, 95% CI = −0.7–0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (−4.8, 95% CI = −7.3 to −2.4 vs −1.0, 95% CI = −1.6 to −0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude. Conclusion Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.

This pilot study examined the functional impact of computerized versus compensatory calendar training in cognitive rehabilitation participants with mild cognitive impairment (MCI). Fifty-seven participants with amnestic MCI completed randomly assigned calendar or computer training. A standard care control group was used for comparison. Measures of adherence, memory-based activities of daily living (mADLs), and self-efficacy were completed. The calendar training group demonstrated significant improvement in mADLs compared to controls, while the computer training group did not. Calendar training may be more effective in improving mADLs than computerized intervention. However, this study highlights how behavioral trials with fewer than 30–50 participants per arm are likely underpowered, resulting in seemingly null findings.

Introduction: This study set out to clarify the differential acute cognitive impact of lorazepam based on varying genetic risk for Alzheimer disease. Methods: Fifty-seven cognitively unimpaired individuals aged 51 to 88, genotyped according to apolipoprotein E (APOE) and translocase of outer mitochondrial membrane (40 homolog) poly-T lengths, completed cognitive testing before, 2.5 and 5 hours after receiving a 1 mg dose of lorazepam. Results: Post-lorazepam, there were significant (P<0.05) declines from baseline in memory, psychomotor processing speed, and executive function. At 2.5 hours, the magnitude of this lorazepam-induced cognitive change was significantly greater in the APOE3/4 group than in the APOE3/3 group for tests of working memory and visuospatial memory/executive function. At 5 hours postchallenge, verbal memory and working memory deficits persisted in the APOE3/4 group compared with the APOE3/3 group. At 5 hours after lorazepam challenge, as compared with the very long/very long group, the short/short group performed slightly worse on a test of working memory (P<0.05), but no other differences were observed among translocase of the outer mitochondrial membrane 40 homolog poly-T variant groups. Discussion: The lorazepam challenge may be unmasking presymptomatic cognitive dysfunction associated with APOE4 carriage.

ObjectiveThis study aims to provide effect size estimates of the impact of two cognitive rehabilitation interventions provided to patients with mild cognitive impairment: computerized brain fitness exercise and memory support system on support partners' outcomes of depression, anxiety, quality of life, and partner burden.MethodsA randomized controlled pilot trial was performed.ResultsAt 6 months, the partners from both treatment groups showed stable to improved depression and anxiety scores, while partners in an untreated control group showed worsening depression and anxiety over 6 months. There were no statistically significant differences on quality of life or burden outcomes in this small pilot trial; however, effect sizes were moderate, suggesting that the sample sizes in this pilot study were not adequate to detect statistical significance.ConclusionEither form of cognitive rehabilitation may help partners' mood or anxiety, compared with providing no treatment. However, effect size estimates related to other partner outcomes (i.e., burden, quality of life) suggest that follow‐up efficacy trials will need sample sizes of at least 30–100 people per group to accurately determine significance. Copyright © 2017 John Wiley & Sons, Ltd.