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. Youden’s index indicated that the optimal cutoff score may be lower than the established cutoff of 26. 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.

Objectives Projections from the United States Census Bureau suggest that the African American population may be the fastest growing race over the next 30 years and that they may be at the highest risk for developing dementia later in life. Various social factors have been shown to be associated with cognitive function and health outcomes. The present study aims to evaluate the relationship between social engagement and cognitive decline in a cohort of older African American adults. Methods We utilized multilevel modeling to examine the association between cognitive decline and social engagement in a sample of 617 older African American adults. Results Social activity was associated with global cognition, perceptual speed, perceptual orientation, and episodic memory over time. Loneliness was associated with better semantic memory performance over time. Perceived discrimination was associated with better semantic memory performance over time. Larger social network was associated with worse perceptual speed scores over time. Conclusions Although our findings on loneliness and perceived discrimination over time were inconsistent with prior research, our findings on social activity and social network size over time were consistent with past literature and are thought to be due to positive social interactions providing a catalyst for cognitively stimulating activities. These results suggest that interventions designed to preserve cognition in African American older adults should incorporate adequate social activity. Furthermore, to maximize effectiveness, interventions should not necessarily focus on just expanding one's social network.

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-β oligomers. We utilized the positron emission tomography (PET) radioligand [ 18 F]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 [ 18 F]FPEB using a bolus-plusconstant-infusion method (K bol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [ 18 F]FPEB binding (BP ND) 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 BP ND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BP ND = 0.76 ± 0.41) compared to CN (BP ND = 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 (BP ND = 1.57 ± 0.25) compared to CN (BP ND = 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: [ 18 F]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.

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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.