Background: Neuropsychiatric symptoms (NPSs) in MCI, and midlife obesity increase the likelihood of developing Alzheimer’s disease. It is unknown whether obesity or related health conditions modify the risk of NPS or severity of cognitive impairment in MCI.Methods: One hundred and thirteen subjects with MCI were assessed near the time of MCI diagnosis. The sample was divided by BMI and related disorders, type-2 diabetes (T2D) and obstructive sleep apnea (OSA) to measure the relationship of these groups with NPS and severity of MCI. NPSs scores were evaluated based on the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and Geriatric Depression Scale, along with NPI-Q clusters. MCI-severity was estimated based on a composite z-score of neuropsychological tests.Results: Obese and overweight subjects represented 65% of the sample and were on average 7 years younger than normal weight subjects. The presence of obesity, T2D and OSA status modified the prevalence and severity of specific NPI-Q symptom clusters, specifically affective symptoms were more frequent across groups and severe in OB and T2D. Total NPS scores were higher for subjects with T2D and OSA although MCI-severity did not differ across groups.Conclusion: MCI subjects with obesity, T2D and OSA demonstrated a higher susceptibility to psychopathologic changes.

We found that MetS was associated with lower neurocognitive function, particularly in midlife. Our findings support and extend current hypotheses that midlife may be a particularly vulnerable developmental period for unhealthy neurocognitive aging.

Introduction Mid‐life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted. Methods Eighty‐seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western‐like/West‐diet vs. Mediterranean‐like/Med‐diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status. Results CSF amyloid beta (Aβ)42/40 ratios increased following the Med‐diet, and decreased after West‐diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West‐diet reduced and the Med‐diet increased total tau (t‐tau), whereas CSF Aβ42/t‐tau ratios increased following the West‐diet and decreased following the Med‐diet. For NC participants, the Med‐diet increased and the West‐diet decreased cerebral perfusion. Discussion Diet response during middle age may highlight early pathophysiological processes that increase AD risk.

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Introduction Sleep and diet are modifiable risk factors for Alzheimer's disease (AD) that may be salient areas for the development of preventive intervention strategies against dementia in people with mild cognitive impairment (MCI). Sleep disturbances account for up to 15% of the population attributable risk for AD. Diet influences sleep quality, such that diets high in sugars, fat, and processed food affect sleep quality and cognition in older adults. The combination of poor sleep and diet health may increase risk for dementia in people with MCI, yet it is unknown how intervening on diet may influence sleep health. Methods The MCI Sleep Study assesses longitudinal changes in objective and subjective measures of sleep between two investigational diet groups in the Brain Energy for Amyloid Transformation in Alzheimer's Disease study: the modified Mediterranean ketogenic diet (MMKD) and the American Heart Association diet. Objective sleep assessments include an in‐home sleep study using the WatchPAT Central Plus (Itamar Medical, Ltd) at baseline and the end of the 4‐month diet intervention. Subjective sleep questionnaires include the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The MCI Sleep Study outcome measures include longitudinal change in cognitive performance, mood, behavior, and quality of life. Results Study recruitment is currently ongoing. We hypothesize the low‐carb MMKD diet to have a beneficial impact on sleep health in individuals with MCI. Pre‐ and post‐diet changes in sleep metrics across diet groups will be examined using mixed effects analysis of variance models. Discussion Early assessment of chronic sleep and diet behaviors may be vital in understanding when interventions are necessary and the lifestyle modifications that should accompany future AD prevention and therapy recommendations.

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Background Cortical thinning is an early marker of Alzheimer’s disease (AD) neurodegenerative changes. We examined relationships of cortical thickness and cerebral blood flow (CBF) to assess whether structural brain changes in AD‐related regions are associated with functional changes in blood flow dynamics. Previous reports of CBF indicate reduced blood flow progressing along the AD continuum from normal cognition (NC) to mild cognitive impairment (MCI) to AD. We hypothesized that reduced cortical thickness in AD‐specific brain regions would relate to reduced global gray matter (GM) CBF. Method Participants enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort (N=373, mean age=70.5 years) underwent neuropsychological assessment, and T1 and pcASL MRI to assess brain structure and CBF. Participants were adjudicated as cognitively unimpaired (NC, N=212) or impaired (MCI or AD, N=161) using NIA‐Alzheimer’s Association criteria. T1 MRI were processed using FreeSurfer v5.3; an “AD‐signature” meta‐ROI cortical thickness value was calculated, which was thresholded to classify participants as neurodegeneration‐negative (N‐, above threshold) or ‐positive (N+, below threshold). PcASL MRI were processed to yield CBF images that were normalized to MNI space (Fig.1). A 2‐tissue partial volume correction was applied to yield voxelwise GM CBF. Mean GM CBF across a set of cortical AAL ROIs was calculated for each participant. A MANCOVA model adjusted for age, sex and education measured differences in GM CBF between N‐ and N+ groups. We additionally assessed cognitive status as a moderator of these associations. Result We found a significant difference in GM CBF between N‐ and N+ groups (p=0.010). Participants with lower meta‐ROI cortical thickness had reduced GM CBF compared to participants above the threshold (Fig.2). The interaction of cognitive status and N+/‐ group revealed lower CBF for impaired participants (Fig.3, unadjusted p<0.001), which remained significant after adjustment (p=0.014). Conclusion In our ADRC cohort, neurodegenerative changes within brain regions vulnerable to AD pathology were associated with global GM CBF reductions. Cognitively unimpaired N+ participants exhibited similar levels of GM CBF as impaired N‐ participants. Future studies will assess whether unimpaired N+ participants with reduced CBF have a higher risk of conversion to MCI or AD.