Comparative Effectiveness of Behavioral Interventions to Prevent or Delay Dementia: One-Year Partner Outcomes.

BACKGROUND/OBJECTIVE: Various behavioral interventions are recommended to combat the distress experienced by caregivers of those with cognitive decline, but their comparative effectiveness is poorly understood. DESIGN/SETTING: Caregivers in a comparative intervention study randomly had 1 of 5 possible interventions suppressed while receiving the other four. Caregivers in a full clinical program received all 5 intervention components. Care partner outcomes in the study group were compared to participants enrolled in a full clinical program. PARTICIPANTS: Two hundred and seventy-two dyads of persons with amnestic mild cognitive impairment (pwMCI) and care partners enrolled in the comparative intervention study. 265 dyads participated in the full clinical program. INTERVENTION: Behavioral intervention components included: memory compensation training, computerized cognitive training, yoga, support group, and wellness education. Each was administered for 10 sessions over 2 weeks. MEASUREMENTS: A longitudinal mixed-effect regression model was used to analyze the effects of the interventions on partner burden, quality of life (QoL), mood, anxiety, and self-efficacy at 12 months follow-up. RESULTS: At 12 months, withholding wellness education or yoga had a significantly negative impact on partner anxiety compared to partners in the clinical program (ES=0.55 and 0.44, respectively). Although not statistically significant, withholding yoga had a negative impact on partner burden and mood compared to partners in the full clinical program (ES=0.32 and 0.36, respectively). CONCLUSION: Our results support the benefits of wellness education and yoga for improving partner's burden, mood, and anxiety at one year. Our findings are the first to provide an exploration of the impact of multicomponent interventions in care partners of pwMCI.

Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriers.

BACKGROUND: Fibrillar amyloid deposition preferentially affects the frontal lobes, temporal pole/neocortex, and posterior cingulate by age 65 years in APOE ε4 carriers prior to the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), but is it impairing frontally mediated neuropsychological performance? METHODS: A total of 71 ε4 homozygotes (HMZ), 194 ε4 heterozygotes (HTZ), and 356 ε4 noncarriers (NC) who did not differ significantly in mean age (56.6 years), years of education (15.6), gender (70% women), or follow-up duration (6.3 years) had neuropsychological testing every 2 years including the Auditory Verbal Learning Test (AVLT) and frontal/executive tasks sensitive to psychomotor speed, working memory, problem solving, and activity. A subset also received the Iowa Gambling Task (IGT). Findings were then tested in a clinical sample of 27 patients with incident MCI and AD. RESULTS: APOE ε4 carriers had greater acceleration of decline (quadratic effect) than NC on the AVLT (p = 0.04) but not on any frontal test. APOE ε4 HMZ had greater velocity of decline (linear effects) than NC on all mental arithmetic tests: paced auditory serial attention task (PASAT) 3 second (p = 0.01) and 2 second (p = 0.004) versions; and Wechsler Adult Intelligence Scale-Revised arithmetic (p = 0.048). IGT performance did not differ between 12 ε4 HMZ, 27 ε4 HTZ, and 44 NC. Among 27 patients with incident MCI and AD, the PASAT showed progressive decline preceding diagnosis in 50%. CONCLUSIONS: No frontal cognitive effects were as robust as memory decline. APOE ε4 HMZ declined more quickly than NC on mental arithmetic tests related to frontal lobe-mediated working memory ability.

Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes.

OBJECTIVE: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype. METHODS: We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two. RESULTS: A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p=0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p<0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons. CONCLUSION: CV risk factors influence age-related memory decline in APOE ε4 HMZ.