Assessing the effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on mRNA transcript levels, Alzheimer’s disease (AD) risk and cognitive performance (P2.163)
Neurology | December 6, 2023 | Volume: 84 | Issue: 14_supplement | Pages: No page available
AbstractBackgroundPartners of persons with mild cognitive impairment (pwMCI) show increased rates of depression and other mental health problems compared to the general population. While dyadic behavioral interventions such as cognitive rehabilitation have shown beneficial effects in reducing caregiver burden, research to date lacks consistent outcome measures and rarely focuses on distressed partners. Therefore, this study explored the longitudinal effect of the Healthy Action to Benefit Independence & Thinking® (HABIT) program on partners with relatively low initial adjustment level. We hypothesized that the HABIT program would improve partner adjustment in those who were distressed.MethodData from 322 pwMCI and partners were utilized from the HABIT IRB research registry. Among them, 240 completed HABIT while 82 served as an untreated control group. Consistent with our previous exploratory factor analysis, a composite partner adjustment score was calculated using the Center for Epidemiologic Studies Depression scale (CES‐D), the REACH Anxiety Inventory Form, and the Quality of Life scale for adults with Alzheimer’s Disease (QOL‐AD). We included partners with an adjustment score below the median of each group to focus on partners with low levels of baseline adjustment. Latent growth curve models were conducted at baseline, 3‐month, 6‐month, and 1‐year follow‐ups to investigate the trajectories of partner adjustment level.ResultIn the low adjustment subsample, no between group difference was found at baseline. An overall improvement in partner adjustment scores was observed only in the treatment group (b = 5.00, p<.001). The slope of change was larger (b = 3.75, p = .016) in the treatment group, indicating a faster improvement in adjustment level in HABIT partners with marginally lower baseline and higher follow‐up scores. This difference in the improvement rates was most evident at the 3‐month follow‐up (t(1, 94) = ‐2.63, p = .010) and gradually reduced in subsequent visits.ConclusionIn partners of those with MCI who have low levels of emotional adjustment, behavioral interventions like HABIT can be beneficial in accelerating improvement in their overall adjustment level and facilitate adaptation to their loved ones’ MCI symptoms compared to untreated controls. Techniques taught in dyadic interventions may serve as protective factors for mental health problems in primary caregivers of pwMCI.
Procedural learning, declarative learning, and working memory as predictors of learning the use of a memory compensation tool in persons with amnestic mild cognitive impairment
AbstractBackgroundEvidence suggests that select hippocampal subfields are implicated in the initial stages of Alzheimer’s disease (AD) and are selectively involved in objective memory. Less is known whether subfields are associated with informant-reported memory difficulties of individuals with a diagnosis of mild cognitive impairment (MCI).MethodData from 56 participants with a diagnosis of amnestic MCI were included in the present study. To test whether FreeSurfer derived hippocampal subfields (CA1–4, subiculum, presubiculum, and dentate gyrus) were associated with objective (learning and delayed recall) and informant-reports of memory difficulties, we used multiple linear regression analysis. Subfields were adjusted for total intracranial volume, and age, sex, and years of education were included as covariates in all models.ResultsLarger presubiculum, subiculum, and CA4/dentate gyrus volumes were associated with higher delayed recall scores, and larger subiculum and CA4/dentate gyrus volumes were associated with fewer informant-reports of memory difficulties. There were no statistically significant associations between subfields and learning scores.DiscussionFindings from the present study support the idea that difficulties with memory-dependent everyday tasks in older adults with MCI may signal a neurodegenerative process while increasing understanding of subfields correlates of these memory-specific functional difficulties. Continued investigations into identifying patterns of subfield atrophy in AD may aid early identification of those at higher risk of dementia conversion while advancing precision medicine.
Longitudinal effects of behavioral interventions: A comparison using a propensity score matching model
Alzheimer's & Dementia | February 1, 2022 | Volume: 17 | Issue: S7 | Pages: No page available
AbstractBackgroundBehavioral interventions are often recommended for persons with mild cognitive impairment (MCI). The Healthy Action to Benefit Independence & Thinking® Program (HABIT) has been shown to benefit activities of daily living (ADL) and self‐efficacy in patients at 6‐ and 12‐months post intervention. However, to date, the findings have been limited by comparison to a relatively small, untreated control group. This study attempted to explore HABIT ADL outcomes compared to a large, presumably untreated Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort.MethodA total of 767 participants with MCI were selected from the ADNI database, whereas 478 participants with MCI were recruited from the HABIT IRB approved research registry. Functional outcomes were assessed with informant‐based measures ‐ Functional Activities Questionnaire (FAQ) and Everyday Cognition scale (ECOG) memory and total scores – at both 6‐month‐ and 12‐month‐follow‐ups. After near‐neighbor propensity score matching with a caliper of 0.2, 288 participants from each group were matched for the FAQ, and 333 were matched for the ECOG scores. Latent growth curve models were used to test the hypothesis that the HABIT program might delay functional decline in patients with MCI.ResultAfter matching HABIT group continued to show higher initial scores on FAQ (b=.849, p=.013), and ECOG memory (b=.200, p=.004) and total scores (b=1.115, p<.001) compared to the ADNI group. Although an increase in scores was observed in both groups for each functional outcome, the slopes were steeper for the HABIT group for FAQ (b=1.194, p<.001), ECOG memory (b=.073, p=.019) and ECOG total (b=.383, p=.007).ConclusionContrary to our hypothesis, in this non‐randomized study, partners of HABIT participants with MCI reported more rapid functional decline compared to those in an imaging study. This discrepancy could be due to the HABIT group’s higher baseline impairment level even after matching. Furthermore, patients with perceived more rapid decline may be more likely to seek interventions relative to those who elect to participate in a non‐interventional imaging study. In addition, the intervention sessions could prime the partners to be more scrupulous and aware when rating functional assessments. Additional randomized research may help add clarity to these findings.
APOE3
-Jacksonville (V236E) variant reduces self-aggregation and risk of dementia
Science Translational Medicine | September 29, 2021 | Volume: 13 | Issue: 613 | Pages: No page available
Background: In Alzheimer’s disease and related disorders (ADRD) research, common outcome measures include cognitive and functional impairment, as well as persons with mild cognitive impairment (pwMCI) and care partner self-reported mood and quality of life. Studies commonly analyze these measures separately, which potentially leads to issues of multiple comparisons and/or multicollinearity among measures while ignoring the latent constructs they may be measuring. Objective: This study sought to examine the latent factor structure of a battery of 12-13 measures of domains mentioned above, used in a multicomponent behavioral intervention (The HABIT® program) for pwMCI and their partners. Methods: Exploratory factor analysis (EFA) involved 214 pwMCI-partner pairs. Subsequent Confirmatory factor analyses (CFA) used 730 pairs in both pre- and post-intervention conditions. Results: EFA generated a three-factor model. Factors could be characterized as partner adjustment (29.9%), pwMCI adjustment (18.1%), and pwMCI impairment (12.8%). The subsequent CFA confirmed our findings, and the goodness-of-fit for this model was adequate in both the pre- (CFI = 0.937; RMSEA = 0.057, p = 0.089) and post-intervention (CFI = 0.942; RMSEA = 0.051, p = 0.430) groups. Conclusion: Results demonstrated a stable factor structure across cohorts and intervention conditions suggesting that three broad factors may provide a straightforward and meaningful model to assess intervention outcome, at least during the MCI phase of ADRD.