Objective:To determine if following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer’s disease (AD), we analyzed cross-sectional data from the German Longitudinal Cognitive Impairment and Dementia StudyMethod:The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 AD relatives, 209 SCD and 81 MCI). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis.Results:Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status.Conclusion:Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.

Objective:We assessed whether novelty-related fMRI activity in medial temporal lobe (MTL) regions and precuneus follows an inverted U-shape pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy.Methods:We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of β-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus and precuneus, as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, gender, study site, and education.Results:In the precuneus, we observed an inverted U-shape pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared to HC, but not in AD patients who showed relatively lower activity than MCI. This non-linear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to precuneus, hippocampal activity was reduced in AD dementia compared to all other groups and related to AD biomarkers.Conclusion:Novelty-related activity in the precuneus follows a non-linear pattern across the clinical spectrum of increased AD risk. While the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the non-linearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity.

Introduction It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves the identification of the initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. Methods Cross‐sectional and longitudinal data from the multicenter, memory clinic–based DELCODE study. Results The SCD group showed slightly worse cognition as well as more subtle functional and behavioral symptoms than the control group (CO). SCD–A+ cases (39.3% of all SCD) showed greater hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms than CO–A+. Amyloid concentration in the CSF had a greater effect on longitudinal cognitive decline in SCD than in the CO group. Discussion Our data suggests that SCD serves the identification of stage 2 of the AD continuum and that stage 2, operationalized as SCD‐A+, is associated with subtle, but extended impact of AD pathology in terms of neurodegeneration, symptoms and clinical progression.

IntroductionThe user experience and clinical effectiveness with wearable global positioning system (GPS) devices for persons with dementia (PwDs) and caregivers (CGs) remain unclear although many are available.MethodsUsing a crossover design, 20 dyads tested two similar commercial GPS watches (products A and B) at home for 4 weeks each. Usability, product functions, design features and product satisfaction at home and the clinic were investigated. Caregiver burden and quality of life assessed clinical effectiveness.ResultsThe final 17 dyads rated the usability, telephone function, overall design features, font, buttons, and battery life of B significantly better than A. PwDs rated the overall design features and buttons of A significantly better than CGs. Product satisfaction with both products was significantly lower at home. Clinical effectiveness was not found.DiscussionUser experience can be improved by optimizing specific product details. This might translate to clinical effectiveness. Social desirability bias may explain different product satisfaction ratings.