studies investigating dietary intake in relation to AD.Our findings suggest that higher adherence to a Western dietary pattern may be associated with pathological levels of AD biomarkers in the preclinical phase of AD. These findings can be added to the increasing amount of evidence linking diet with AD and may be useful for future intervention studies investigating dietary intake in relation to AD. We and collaborators discovered that flickering lights and sound at gamma frequency (40Hz) reduce Alzheimer's disease (AD) pathology and alter immune cells and signaling in mice. To determine the feasibility of this intervention in humans we tested the safety, tolerability, and daily adherence to extended audiovisual gamma flicker stimulation. Ten patients with mild cognitive impairment due to underlying AD received 1-hour daily gamma flicker using audiovisual stimulation for 4 or 8weeks at home with a delayed start design. Gamma flicker was safe, tolerable, and adherable. Participants' neural activity entrained to stimulation. Magnetic resonance imaging and cerebral spinal fluid proteomics show preliminary evidence that prolonged flicker affects neural networks and immune factors in the nervous system. These findings show that prolonged gamma sensory flicker is safe, tolerable, and feasible with preliminary indications of immune and network effects, supporting further study of gamma stimulation in AD.These findings show that prolonged gamma sensory flicker is safe, tolerable, and feasible with preliminary indications of immune and network effects, supporting further study of gamma stimulation in AD.Elderly persons with currently normal cognition who have cerebral hypometabolism as shown by low uptake of 18fluorine-fluorodeoxyglucose (18F-FDG), are at risk of future loss of cognition and, thus, of future Alzheimer's dementia (AD). Reduction of either 18F-FDG or cognition is assumed to reflect synaptic dysfunction, since synapses account for the majority of glucose use by the brain and cognition depends upon accurate synaptic function. The chronology of the connection between reduced cerebral synaptic function and hypometabolism is, therefore, a critical question, because if synaptic dysfunction came first, then correcting the hypometabolism would likely not benefit synaptic function; but if hypometabolism came first, then correcting the hypometabolism probably would benefit synaptic function. That correction might prevent initiation of the cognitive loss that eventuates in AD and, thereby, would benefit the vast numbers of persons in their eighth to tenth decades of life who are at risk for AD. Among the many citations reviewed in this presentation, seven show hypometabolism that precedes synaptic dysfunction, and two show the reverse. Thus the preponderance of evidence, 78%, suggests that the initiating event is synaptic hypometabolism and that it is 3.5-fold less likely that synaptic dysfunction is the initiator. In addition, it is inherently unlikely that synaptic dysfunction causes hypometabolism. This conclusion could be tested by a clinical trial whose primary objective would be to assess the benefit to cognition of improving synaptic metabolism in patients who are at risk for cognitive loss. To study if declining cognition drives weight loss in preclinical dementia, we examined the longitudinal association between body mass index (BMI) and cognitive abilities in individuals who did or did not later develop dementia. Using data from individuals spanning age 50 to 89, we applied dual change score models separately in individuals who remained cognitively intact (n=1498) and those who were diagnosed with dementia within 5 years of last assessment (n=459). Among the cognitively intact, there was a bidirectional association Stable BMI predicted stable cognition and vice versa. Among individuals who were subsequently diagnosed with dementia, the association was unidirectional Higher BMI predicted declining cognition but cognition did not predict change in BMI. Although BMI and cognition stabilized each other when cognitive functioning was intact, this buffering effect was missing in the preclinical dementia phase. This finding indicates that weight loss in preclinical dementia is not driven by declining cognition.Although BMI and cognition stabilized each other when cognitive functioning was intact, this buffering effect was missing in the preclinical dementia phase. This finding indicates that weight loss in preclinical dementia is not driven by declining cognition. Prospective studies investigating flavonoid intake and dementia risk are scarce. The aims of this study were to examine associations between flavonoid intake and the risk of incident dementia and to investigate whether this association differs in the presence of lifestyle risk factors for dementia. We examined associations in 55,985 participants of the Danish Diet, Cancer, and Health Study followed for 23 years. The Phenol-Explorer database was used to estimate flavonoid intakes. Information on incident dementia and dementia subtypes was obtained using Danish patient and prescription registries. Hazard ratios (HRs) were calculated using restricted cubic splines in multivariable-adjusted Cox proportional hazards models. For incident dementia, moderate compared to low intakes of flavonols (HR 0.90 [0.82, 0.99]), flavanol oligo+polymers (HR 0.87 [0.79, 0.96]), anthocyanins (HR 0.84 [0.76, 0.93]), flavanones (HR 0.89 [0.80, 0.99]), and flavones (HR 0.85 [0.77, 0.95]) were associated with a lower risk. For vascular dementia, moderate intakes of flavonols (HR 0.69 [0.53, 0.89]) and flavanol oligo + polymers (HR 0.65 [0.51, 0.83]) were associated with lower risk. selleck inhibitor Flavonoid intakes were not significantly associated with Alzheimer's disease or unspecified dementia. The inverse association between total flavonoid intake and incident dementia was stronger in "ever" smokers than in "never" smokers and in those without hypercholesterolemia versus those with hypercholesteremia. Furthermore, the inverse association of vascular dementia with a moderate total flavonoid intake was stronger in "ever" smokers and those who were "normal" to "overweight" versus "never" smokers or those who were "obese," respectively. A moderate intake of flavonoid-rich foods may help to reduce dementia risk.A moderate intake of flavonoid-rich foods may help to reduce dementia risk.