Specific and cumulative infection burden and mild cognitive impairment and dementia: A population-based study.

Infection by pathogenic microbes is widely hypothesized to be a risk factor for the development of neurocognitive disorders and dementia, but evidence remains limited. We analyzed the association of seropositivity to 11 common pathogens and cumulative infection burden with neurocognitive disorder (mild cognitive impairment and dementia) in a population-based cohort of 475 older individuals (mean age = 67.6 y) followed up over 3-5 years for the risk of MCI-dementia. Specific seropositivities showed a preponderance of positive trends of association with MCI-dementia, including for Plasmodium, H. pylori, and RSV (p < 0.05), as well as Chickungunya, HSV-2, CMV and EBV (p > 0.05), while HSV-1 and HHV-6 showed equivocal or no associations, and Dengue and VZV showed negative associations (p < 0.05) with MCI-dementia. High infection burden (5 + cumulated infections) was significantly associated with an increased MCI-dementia risk in comparison with low infection burden (1-3 cumulative infections), adjusted for age, sex, and education. Intriguingly, for a majority (8 of 11) of pathogens, levels of antibody titers were significantly lower in those with MCI-dementia compared to cognitive normal individuals. Based on our observations, we postulate that individuals who are unable to mount strong immunological responses to infection by diverse microorganisms, and therefore more vulnerable to infection by greater numbers of different microbial pathogens or repeated infections to the same pathogen in the course of their lifetime are more likely to develop MCI or dementia. This hypothesis should be tested in more studies.

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Healthy elderly Singaporeans show no age-related humoral hyporesponsiveness nor diminished plasmablast generation in response to influenza vaccine.

ABSTRACT: Improving influenza vaccine efficacy is a priority to reduce the burden of influenza-associated morbidity and mortality. By careful selection of individuals based on health we show sustained response to influenza vaccination in older adults. Sustaining health in aging could be an important player in maintaining immune responses to influenza vaccination. TRIAL REGISTRATION: NCT03266237. Registered 30 August 2017, https://clinicaltrials.gov/ct2/show/NCT03266237.

Prevalence and severity of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Chinese: findings from the Shanghai three districts study.

OBJECTIVES: Studies of the prevalence and risk factors for behavioral and psychological symptoms of dementia (BPSD) have primarily been conducted in nursing home and clinic populations. Few population-based studies have been conducted in community-living persons with dementia. METHODS: In this cross-sectional study, persons aged 65 and above who were living in the community were screened for dementia with the Chinese version of Mini-Mental State Examination (CMMSE) and Ability of Daily Living (ADL-14) scale. Participants with a diagnosis of dementia according to DSM-IV criteria made by trained neuropsychiatrists s were with the Neuropsychiatric Inventory assessed for BPSD by informant interview. RESULTS: Among 1271 persons with dementia, 50.1% had at least one BPSD. Sleep disturbance was the most common symptom (21.9%), followed by irritability (19.6%), and apathy (15.7%). About 40% (N = 501) of these problems were clinically significant (NPI score > 4). The NPI score was significantly associated with the CMMSE score, ADL score and education. CONCLUSION: BPSD are common among community living Chinese people with dementia, but the relatively lower prevalence rate and different pattern of symptoms from those reported in the USA, UK and Japan suggest the possible influence of cultural background and psychosocial environment.

Subsyndromal depression in old age: clinical significance and impact in a multi-ethnic community sample of elderly Singaporeans.

OBJECTIVE: This cross-sectional study examined the clinical significance and impact of subsyndromal depression in a sample of elderly people living in the community in Singapore. METHOD: Data were analyzed from a population survey (the Singapore National Mental Health Survey of the Elderly). A total of 1092 respondents from a nationally representative multi-ethnic (Chinese, Malay and Indian) stratified random sample of older adults aged 60 and above were examined for depression using the Geriatric Mental State Examination (GMS). Diagnostic confidence levels of 3-5 indicated a DSM-IV diagnosis of syndromal depression, and 1-2 indicated subsyndromal depression. Other variables included sociodemographic characteristics, psychiatric and medical comorbidities, MMSE, health awareness, health and functional status. RESULTS: Subjects with subsyndromal depression were more likely to have poor socioeconomic status, cognitive impairment, anxiety, and measures of poor mental, physical and functional status compared with non-depressed subjects, and were similar to or worse than syndromal cases. In multivariate analyses that controlled for age, gender, ethnicity, education and several other sociodemographic factors, both subsyndromal and syndromal depression were significantly associated with higher numbers of medical comorbidities, diagnoses of comorbid dementia and anxiety, lower MMSE scores, self-reported mental health problem, functional disability and poor health status. CONCLUSION: In this Asian population, subsydromal depression had the same clinical significance and health impact as syndromal depression, similar to findings in the West.