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Background: The association of late‐life hypertension (LHTN) with Alzheimer's disease (AD) remains controversial. We hypothesize that FOXO3 longevity‐associated genotype modulates the association between LHTN and incident AD. Method: Subjects were 2,688 American men of Japanese ancestry (baseline age: 77.0 ± 4.1 years, range 71‐93 years) from the Kuakini Honolulu Heart Program. Status was known for FOXO3 rs2802292 genotype, LHTN at baseline, and diagnosis of incident dementia over 21 years follow‐up. Association of FOXO3 genotype with LHTN and incident all‐cause dementia, vascular dementia (VD) and Alzheimer's disease was assessed using Cox regression. Result: During the follow‐up, 725 men were diagnosed with all‐cause dementia, 513 with AD and 104 with VD. A multivariable Cox model, adjusting for age, education, APOE‐ε4 and cardiovascular risk factors, showed LHTN increased VD risk (HR = 1.71, 95%CI = 1.08–2.71, p = 0.022), but not AD risk. We found no significant protective effect of FOXO3 longevity genotype, nor of LHTN, on all‐cause dementia and AD at the population level. However, in a full Cox model adjusting for age, education, APOE‐ε4 and other cardiovascular risk factors, there was a significant interaction effect of LHTN and FOXO3 longevity genotype on incident AD (ß = –0.52, p = 0.0061). In men with FOXO3 rs2802292 longevity genotype (TG/GG), LHTN showed protection against AD (HR = 0.72; 95% CI = 0.55–0.95, p = 0.021). In men with FOXO3 rs2802292 non‐longevity genotype (TT), LHTN had no protective effect (HR = 1.16; 95% CI = 0.90‐1.51, p = 0.25). Discussion: Since the effect of LHTN on AD incidence differed according to FOXO3 genotype, the overall effect, namely, a weighted average effect of LHTN on AD across different FOXO3 genotypes, would be moving towards the null (i.e., HR = 1). This would explain why most studies have found no significant association between LHTN and AD. One exception is the Ibadan study, in which all participants were African American. African Americans have the highest proportion (94%) of FOXO3 rs2802292 longevity genotype (TG/GG) in all races, and the strongest effect of LHTN in protecting against AD (RR = 0.33). Conclusion: This longitudinal study found that FOXO3 genotype modulates the effect of late‐life hypertension on incident AD, thus explaining the conflicting data on late‐life hypertension and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: We assessed the longitudinal association between social networks in late life and the incidence of all‐cause dementia (DEM), Alzheimer's disease (AD) and vascular dementia (VaD) over a 10‐year follow‐up period in a community‐based cohort of older Japanese‐American men. Method: This prospective study analyzed data from cognitively intact participants of the Kuakini Honolulu‐Asia Aging Study (K‐HAAS). The K‐HAAS began with the Kuakini Honolulu Heart Program's fourth examination in 1991‐1993, which served as our baseline timepoint. We followed 2,636 Japanese‐American men through the seventh exam (1999‐2000). Participants were dementia‐free at baseline and during the first 3 years of follow‐up. Social network strength was assessed by the Lubben Social Network Scale (LSNS). Weak and strong social network groups were defined by a median split of LSNS scores. Global cognitive functioning was evaluated by the Cognitive Abilities Screening Instrument (CASI), and depressive symptoms by the Center for Epidemiologic Studies Depression (CES‐D) 11‐item Scale. Dementia was diagnosed and classified by consensus of neurologists and geriatricians using standard criteria. Associations between baseline LSNS scores and the risks of DEM, AD and VaD were evaluated by multivariable Cox regression and Kaplan‐Meier estimators using age as the time scale. Result: Study participants had a median (range) baseline age of 77 (71‐93) years. The age‐adjusted incidence of DEM was significantly higher among men who had weak (LSNS score ≤29) vs. strong (>29) social networks (12.6 vs. 8.7 per 1,000 person‐years of follow‐up; p = 0.014). Kaplan‐Meier survival curves showed that the men with strong social networks were less likely to develop DEM (p<0.0001) and AD (p = 0.0006); the probability of DEM‐free survival at almost 10 years was 93.8% for participants with strong social networks and 89.0% (11% incidence) for those with weak networks. In Cox regression models adjusting for baseline age, education, presence of at least one ApoE ɛ4 allele, prevalent stroke, depressive symptoms (CES‐D score ≥9), and CASI score, weak social networks were significantly associated with increased risk of DEM (HR = 1.52, 95%CI = 1.11‐2.08, p = 0.009) and AD (HR = 1.67, 95%CI = 1.11‐2.51, p = 0.014). Conclusion: Strong social networks may protect against incident dementia and Alzheimer's disease. Effective strategies should be devised to prevent the social isolation of older adults. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are cardinal symptoms of dementia. They are often associated with functional decline, poor quality of life, and caregiver burden. Anecdotal reports have suggested increase in NPS during the COVID pandemic. However, decreased time demands on the caregivers could be hypothesized to have improved relationships and indirectly NPS. There has been limited literature on whether NPS improved or worsened during the current pandemic. The current study examines the prevalence of NPS and changes in NPS profile during the pandemic. Loneliness, cognition, function, and caregiver distress were also studied. Methods: The COVID Dementia study is an ongoing cross‐sectional study of community dwelling cognitively impaired older adults (N=102). Loneliness was assessed with the 3‐item loneliness questionnaire, cognition with the Tele‐Montreal Cognitive Assessment (T‐MoCA), and functional status with the Functional Activities Questionnaire (FAQ). Neuropsychiatry symptoms including severity and distress were collected using the Neuropsychiatric Inventory (NPI) and change during COVID was also recorded for each symptom. Results: Mean age was 73.0 (±8.0) years, 96.1% male, 42.2% rural, 75.2% Caucasian, and 24.8% non‐Caucasian. T‐MoCA and FAQ mean scores were 15.2 (±4.6) and 8.0 (±9.3), respectively. Loneliness was prevalent in majority of participants (53.5%). Mean loneliness score was 4.7 (±2.1). Mean NPI total severity and total distress were 7.5 (±6.5) and 10.9 (±8.8), respectively. Irritability and night‐time behavior were most frequently reported symptoms (45.7% each), followed by anxiety (45.3%), and agitation (41.1%). Majority of the participants reported worsening of neuropsychiatric symptoms during COVID (61.5%). Irritability, agitation, and anxiety was the cluster that was reported as most frequently worsened symptoms during the pandemic followed by depression and apathy cluster (Fig. 1). Among those that reported worsening of neuropsychiatric symptoms, 66.1% noted an increase in ≥ two symptoms. Conclusions: Older adults with pre‐existent cognitive impairment may be at high risk for loneliness and worsening of neuropsychiatric symptoms during the COVID pandemic. Some NPS might worsen more frequently during the pandemic and need particular attention. [ABSTRACT FROM AUTHOR]

Background: Loneliness in older adults is multifactorial. Social connectedness and resilience are protective against loneliness and have been adversely affected by the COVID pandemic. The objective was to measure loneliness in older adults with and without cognitive impairment and to compare the interaction of loneliness with resilience and social connectedness in these subgroups. Methods: A cross‐sectional study was conducted in community dwelling older adults (N=254) (November 2020‐ongoing). Demographic data were collected along with variables related to social determinants of health. Loneliness was assessed with the 3‐item loneliness questionnaire, resilience with the Brief Resilience Coping Scale (BRCS) and social connectedness using the 6‐item Lubben social network scale. Results: Mean age was 74.6 (±8.0) years, 93.7% male, 50.8% rural, 79.5% Caucasian, and 17.3% African American. Mean education was 14 years (±2.4). The majority of the participants reported loneliness (57.5%). Mean Lubben social network score was 14.7 (±7.1) and mean resilience score was 15.0 (±4.1). Loneliness was higher in those living alone compared to those living with someone (5.6 vs. 4.6, p<0.001, 95% CI: ‐1.6, ‐0.48). There were strong negative correlations between social connectedness and loneliness (p<0.001, r=‐0.43) and resilience and loneliness (p=0.001, r=‐0.19). Compared to those without cognitive impairment (N=151), participants with cognitive impairment (N=101) had a significantly lower mean social network score (p=0.007, 95% CI: 0.69, 4.23). Compared to those without cognitive impairment, participants with cognitive impairment had lower mean resilience score, however the difference was not statistically significant (p=0.080, 95% CI: ‐0.11, 1.97). T‐MoCA and FAQ mean scores for the cognitively impaired older adults were 15.2 (±4.6) and 8.0 (±9.3), respectively. The strong negative correlation between resilience and loneliness scores persisted in the subgroup with cognitive impairment (p=0.028, r=‐0.22). Conclusions: Loneliness was commonly reported among older adults during the COVID pandemic. Loneliness was negatively correlated with social connectedness and resilience. Compared to cognitively intact counterparts, those with cognitive impairment reported significantly lower social connectedness. This finding indicates that those with cognitive impairment may need more attention during natural disasters that foster physical separation. [ABSTRACT FROM AUTHOR]