Longitudinal Predictors of Informant-Rated Everyday Function in Mild Cognitive Impairment.

OBJECTIVE: To examine predictors of informant-reported everyday functioning in mild cognitive impairment (MCI) and relations between everyday function and conversion to dementia. METHODS: Informants of participants (n = 2614) with mild cognitive impairment (MCI) were administered the Functional Activities Questionnaire (FAQ). Changes in dimensions of functional ability as determined by an exploratory factor analysis (EFA) were examined over 3 years and participant predictors of change were examined using multilevel modeling (MLM). RESULTS: The FAQ consisted of 3 factors, multistep, finance, and memory/orientation daily tasks. Impairment in memory/orientation tasks was significantly higher than impairment in multistep tasks. Worse functioning was associated with greater depression, worse memory, worse speed/EF, higher years of education and identifying as White. There was variability in some of these associations with different FAQ factors. Impairments in financial and memory/orientation daily tasks predicted follow-up conversion to dementia. CONCLUSIONS: Depression, speed/EF, and memory are consistently associated with domains of everyday functioning. Race, education, and age may be more variability associated with everyday functioning. Specific attention should be paid to subtle declines in the financial and memory/orientation domains as they may uniquely predict future dementia development. Depression may be a modifiable risk factor associated with functional impairment over time.

Impact of COVID-19 Pandemic on Research Participation Among Older African Americans.

COVID-19 represents the newest health disparity faced by African Americans (AA). This study assessed the impact of COVID-19 on barriers and willingness to participate in research among older AAs. An online survey was sent to a nationwide sample of 65- to 85-year-old AAs between January and February 2021. Constant comparison analysis was used to extract themes. A total of 624 older AAs completed the survey. Approximately 40% of participants were willing to engage in virtual or in-person research. Of the individuals who were willing to participate in research, >50% were willing to engage in a spectrum of activities from group discussions to group exercise. Research participation themes related to logistics, technology, pandemic fears, and privacy or security. Older AAs face new research barriers that can be overcome through data use transparency and technology resources. This information can be used to encourage dementia research engagement among older AAs despite the pandemic.

Statin Use and Risk of Cognitive Decline in the ADNI Cohort.

OBJECTIVE: To investigate associations between statin use and cognitive change, as well as diagnostic conversion, in individuals with cognitively normal (CN) status, mild cognitive impairment (MCI), and dementia due to Alzheimer disease (AD-dementia). METHODS: A multicenter cohort study with 1629 adults 48 to 91 years old with CN status, early MCI (EMCI), late MCI (LMCI), or AD-dementia at baseline followed prospectively for 24 months. Statin use was assessed at baseline, and cognition was measured over time with a composite memory score, a composite executive function score, and a global cognition score (Alzheimer's Disease Assessment Scale). Conversion to a more impaired diagnostic category was determined by clinician assessment. Repeated measures linear mixed-effects models were used to evaluate associations between statin use and change in cognition over time. Cox proportional hazards models were used to evaluate associations between statin use and time to diagnostic conversion. All models were stratified by baseline diagnostic group. RESULTS: Statin use was not associated with change in cognitive measures for CN, LMCI, or AD-dementia participants. Among EMCI participants, statin use was associated with a significantly slower rate of decline on the memory composite, but no other cognitive measure. Statin use was not associated with time to conversion for any diagnostic group. CONCLUSIONS: This study did not support an association between statin use and diagnostic conversion but suggested a possible association between statin use and cognitive change in EMCI. Additional randomized clinical trials of statins may be warranted in the prodromal EMCI stage of AD.

Effects of Normative Adjustments to the Montreal Cognitive Assessment.

OBJECTIVE: To investigate optimal cutoff scores and the effects of normative adjustments on the performance of the Montreal Cognitive Assessment (MoCA) as a screening instrument for Mild Cognitive Impairment (MCI) and dementia due to Alzheimer's disease (AD-dementia). METHODS: 499 adults 48 to 91 years-old enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and were administered the MoCA during baseline. Participants were classified as either cognitively normal (CN), MCI, or AD-dementia by clinical assessment. Receiver operating characteristic (ROC) analyses were performed using raw MoCA scores, education-adjusted MoCA scores, and a regression-based adjustment derived from the National Alzheimer's Coordinating Center data (NACC). Test performance characteristics were calculated for various cutoffs after each normative correction method. RESULTS: Areas under the curve (AUC) were similar for raw, education-adjusted, and NACC-adjusted MoCA scores, and demonstrated minimal improvement when adjustments of increasing complexity were applied. Our results suggest that the optimal cutoff score for distinguising MCI is 24 and for distinguising AD-dementia is 22. CONCLUSIONS: This study adds to the understanding of how normative adjustments affect the sensitivity and specificity of the MoCA. Suggested corrections based on education alone do not yield improved test characteristics, but small improvements are attained when a regression-based correction that accounts for age, sex, and education is applied. Furthermore, optimal cutoffs for distinguishing CN from MCI or CN from AD-dementia were lower than previously reported. Optimal cutoffs to detect MCI and AD-dementia may vary in different populations, and further study is needed to determine appropriate use of the MoCA as a screening tool.

Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort.

BACKGROUND: We investigated the relationship between sleep disturbance and cognitive decline or clinical conversion in individuals with normal cognition (CN), as well as those with mild cognitive impairment (MCI) and dementia due to Alzheimer disease (AD-dementia). METHODS: Secondary analysis of 1,629 adults between 48 and 91 years of age with up to 24 months of follow-up from the ADNI (Alzheimer's Disease Neuroimaging Initiative), a longitudinal cohort study. RESULTS: Sleep disturbance was not associated with decline in memory, executive function, or global cognition. The presence of sleep disturbance did not significantly increase the risk of diagnostic conversion in CN, early MCI, or late MCI participants. CONCLUSION: This study investigated the effect of sleep disturbance on cognitive decline using several outcomes and does not support the hypothesis that sleep disturbance predicts subsequent cognitive decline.

Examining the factor structure of the Rey auditory verbal learning test in individuals across the life span.

Objective: Previous studies analyzing the factor structure of the Rey Auditory Verbal Learning Test (RAVLT) have been limited in the number of scores included in the analysis. Often, they lacked inclusion of process scores that have been shown to add predictive value in identifying future cognitive decline. Therefore, the goal of the current study was to determine the factor structure of the RAVLT utilizing factor scores including serial position effects, repetitions, and intrusion errors, and to examine if the factor structure for older adults is similar to that found in the entire lifespan sample.Method: Exploratory factor analysis (EFA) was conducted on 718 participants (age 16-85 years) from the Nathan Kline Institute (NKI)-Rockland project. Confirmatory factor analyses (CFA) of a reduced model of the EFA was conducted on the entire sample and an older (ages 55-85 years; n = 265) and a younger (less than 55 years of age; n = 453) subsample.Results: EFA indicated three factors: Memory, Attention/Learning, and Inaccurate Memory (i.e., repetitions and intrusions). CFA of a reduced model indicated adequate fit in the entire sample and older subsample, and good fit in the younger subsample.Conclusion: The present study examined the factor structure of the RAVLT in a large lifespan sample utilizing a larger set of RAVLT scores than have been examined in prior studies, including total scores and process scores. The same factors were identified in the entire lifespan sample and the younger and older adult subsamples, although similar to previous studies, measures of model fit were less robust in the older adult subsample. These results provide additional support for the error scores (e.g., intrusions and repetitions) as separable from other aspects of learning and memory.

PET imaging of mGluR5 in Alzheimer's disease.

BACKGROUND: Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-ß oligomers. We utilized the positron emission tomography (PET) radioligand [18F]FPEB to investigate mGluR5 binding in early AD. METHODS: Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [18F]FPEB using a bolus-plus-constant-infusion method (Kbol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [18F]FPEB binding (BPND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects. RESULTS: Linear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BPND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BPND = 0.76 ± 0.41) compared to CN (BPND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BPND = 1.57 ± 0.25) compared to CN (BPND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function. CONCLUSIONS: [18F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments.