Higher Risk Of Dementia Research Articles

Associations of Serum GDF-15 Levels with Physical Performance, Mobility Disability, Cognition, Cardiovascular Disease, and Mortality in Older Adults.

Growth differentiation factor 15 (GDF-15) is a member of the TGFβ superfamily secreted by many cell types and found at higher blood concentrations as chronological age increases (1). Given the emergence of GDF-15 as a key protein associated with aging, it is important to understand the multitude of conditions with which circulating GDF-15 is associated. We pooled data from 1,174 randomly selected Health ABC Study (Health ABC) participants and 1,503 Cardiovascular Health Study (CHS) participants to evaluate the risk of various conditions and age-related outcomes across levels of GDF-15. The primary outcomes were (1) risk of mobility disability and falls; (2) impaired cognitive function; (3) and increased risk of cardiovascular disease and total mortality. The pooled study cohort had a mean age of 75.4 +/-4.4 years. Using a Bonferroni-corrected threshold, our analyses show that high levels of GDF-15 were associated with a higher risk of severe mobility disability (HR: 2.13 [1.64, 2.77]), coronary heart disease (HR: 1.47 [1.17, 1.83]), atherosclerotic cardiovascular disease (HR: 1.56 [1.22, 1.98]), heart failure (HR: 2.09 [1.66, 2.64]), and mortality (HR: 1.81 [1.53, 2.15]) when comparing the highest and lowest quartiles. For CHS participants, analysis of extreme quartiles in fully adjusted models revealed a 3.5-fold higher risk of dementia (HR: 3.50 [1.97, 6.22]). GDF-15 is associated with several age-related outcomes and diseases, including mobility disability, impaired physical and cognitive performance, dementia, cardiovascular disease, and mortality. Each of these findings demonstrates the importance of GDF-15 as a potential biomarker for many aging-related conditions.

Dementia Incidence in Survivors of Multiple Myeloma: A National Case-Control Study Conducted in Korea (The CAREMM-2106 Study)

BackgroundDementia, a growing global health issue, affects older adults and specific groups like long-term cancer survivors. The link between cancer survival and dementia is debated. Multiple myeloma (MM), a common blood cancer in older adults, is often linked with cognitive issues. This study investigated dementia incidence in long-term MM survivors using Korean national data. MethodsA retrospective case-control study used data from the Korea National Health Insurance Service (KNHIS), covering about 50 million Koreans. Patients diagnosed with MM between 2009 and 2020 formed the case cohort, while the control cohort included matched individuals without MM using propensity-score matching. Analyzing baseline characteristics, comorbidities, and socioeconomic status, the primary outcome was dementia incidence identified via ICD-10 codes. Statistical methods included Kaplan-Meier plots, cause-specific and Fine–Gray subdistribution hazard models, and a 3-year landmark analysis for immortal time bias. ResultsThe study included 33,864 patients, with 16,932 in each cohort. The overall cumulative dementia incidence was lower in the MM cohort compared to controls. However, in the first 3 years, MM patients had a higher dementia risk (HR: 1.711, 95% CI, 1.562-1.874) than controls. After 3 years, the risk significantly decreased (HR: 0.625, 95% CI, 0.560-0.696). Age-specific analysis showed a consistent pattern, particularly among MM patients aged 70-79, where dementia risk increased post-3 years. ConclusionThis study reveals a lower long-term dementia risk in MM survivors compared to non-MM individuals. Further prospective studies are needed to confirm these findings and explore the underlying mechanisms.

House dust mite-induced asthma exacerbates Alzheimer’s disease changes in the brain of the AppNL-G-F mouse model of disease

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal death. Besides aging, various comorbidities increase the risk of AD, including obesity, diabetes, and allergic asthma. Epidemiological studies have reported a 2.17-fold higher risk of dementia in asthmatic patients. However, the molecular mechanism(s) underlying this asthma-associated AD exacerbation is unknown. This study was designed to explore house dust mite (HDM)-induced asthma effects on AD-related brain changes using the AppNL-G-F transgenic mouse model of disease. Male and female 8–9 months old C57BL/6J wild type and AppNL-G-F mice were exposed to no treatment, saline sham, or HDM extract every alternate day for 16 weeks for comparison across genotypes and treatment. Mice were euthanized at the end of the experiment, and broncho-alveolar lavage fluid (BALF), blood, lungs, and brains were collected. BALF was used to quantify immune cell phenotype, cytokine levels, total protein content, lactate dehydrogenase (LDH) activity, and total IgE. Lungs were sectioned and stained with hematoxylin and eosin, Alcian blue, and Masson’s trichrome. Serum levels of cytokines and soluble Aβ1-40/42 were quantified. Brains were sectioned and immunostained for Aβ, GFAP, CD68, and collagen IV. Finally, frozen hippocampi and temporal cortices were used to perform Aβ ELISAs and cytokine arrays, respectively. HDM exposure led to increased levels of inflammatory cells, cytokines, total protein content, LDH activity, and total IgE in the BALF, as well as increased pulmonary mucus and collagen staining in both sexes and genotypes. Levels of serum cytokines increased in all HDM-exposed groups. Serum from the AppNL-G-F HDM-induced asthma group also had significantly increased soluble Aβ1-42 levels in both sexes. In agreement with this peripheral change, hippocampi from asthma-induced male and female AppNL-G-F mice demonstrated elevated Aβ plaque load and increased soluble Aβ 1–40/42 and insoluble Aβ 1–40 levels. HDM exposure also increased astrogliosis and microgliosis in both sexes of AppNL-G-F mice, as indicated by GFAP and CD68 immunoreactivity, respectively. Additionally, HDM exposure elevated cortical levels of several cytokines in both sexes and genotypes. Finally, HDM-exposed groups also showed a disturbed blood–brain-barrier (BBB) integrity in the hippocampus of AppNL-G-F mice, as indicated by decreased collagen IV immunoreactivity. HDM exposure was responsible for an asthma-like condition in the lungs that exacerbated Aβ pathology, astrogliosis, microgliosis, and cytokine changes in the brains of male and female AppNL-G-F mice that correlated with reduced BBB integrity. Defining mechanisms of asthma effects on the brain may identify novel therapeutic targets for asthma and AD.

Estimated Pulse Wave Velocity Is Associated With a Higher Risk of Dementia in the Health and Retirement Study.

In this paper, we use the Health and Retirement Study (HRS) to examine the relationship between an estimated measure of pulse wave velocity (ePWV) and cognitive impairment with no dementia and dementia, respectively. We modeled the relationship between ePWV and cognitive status in 2006/2008 using data from 8,492 men and women (mean age 68.6 years) controlling for age, blood pressure, sociodemographic, and socioeconomic characteristics (sex, race and ethnicity, education, income, wealth), health behaviors (smoking and physical activity), body mass index (BMI), health status and related medication use (history of cardiovascular disease, diabetes, and stroke), and cerebrovascular disease (CVD)-related biomarkers (C-reactive protein, cystatin-C, hemoglobin A1c, total cholesterol, high-density lipoprotein [HDL] cholesterol). We assess cognitive function with the 27-item Langa-Weir Telephone Interview for Cognitive Status (TICS) scale. ePWV is derived from an equation based on participant age and resting blood pressure. In a model that controlled for the constituent components of ePWV (age, age squared, systolic and diastolic blood pressure), ePWV is associated with increased odds of having cognitive impairment with no dementia (OR = 2.761) and dementia (OR = 6.344) relative to a group with no cognitive impairment or dementia. After controlling for the constituent components of ePWV, sociodemographic and socioeconomic characteristics, health behaviors, BMI, health status and medication use, and CVD-related biomarkers, ePWV remains significantly associated with dementia (OR = 3.969) but not cognitive impairment with no dementia (OR = 1.782). These findings suggest that ePWV may be a novel research tool and biomarker of vascular aging that can be used in large, population-representative studies to examine cognitive aging and dementia risk.

Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease.

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with a higher risk of dementia and, consequently, be not rarely misdiagnosed. In this review, we summarize the current understanding of LBD-AD by discussing the synergistic effects of AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment for use in LBD-AD and their possible diagnostic and prognostic values. AD pathology can be predicted in vivo by means of CSF, MRI and PET markers, whereas the most promising technique to date for identifying Lewy pathology in different biological tissues is the α-synuclein seed amplification assay. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity as in pure AD. Implementing the use of blood-based AD biomarkers might allow faster screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account when considering differential diagnoses of dementia syndromes, to allow prognostic evaluation on an individual level, and to guide symptomatic and disease-modifying therapies.

A Longitudinal Study of CogEvo's Prediction of Cognitive Decline in Older Adults.

The predictive abilities of computer-based screening devices for early cognitive decline (CD) in older adults have rarely been longitudinally examined. Therefore, this study examined the ability of CogEvo, a short-duration, computer-based cognitive screening device requiring little professional involvement, to predict CD among community-dwelling older adults. We determined whether 119 individuals aged ≥ 65 years living in Japanese rural communities who scored ≥ 24 on the Mini-Mental State Examination (MMSE) at baseline developed CD by annually administering the MMSE to them. CD was defined as an MMSE score of ≤23. At baseline, the overall CogEvo judgment grade, with lower grades indicating better cognitive function, was calculated from the results of various cognitive tasks. Over 2 years, 10 participants developed CD. Participants with grades of 4 had a higher percentage of CD cases than those with grades of ≤3 (p < 0.01). This relationship remained significant after controlling for possible confounders, including the MMSE score at baseline. The sensitivity and specificity of the CogEvo grade cutoff of 4 were 50.0% and 93.6%, respectively. In conclusion, CogEvo may be an efficient tool for identifying individuals at a high risk for dementia. The possibility of missing CD cases should be considered when using CogEvo for screening.

Cerebral arteriolosclerosis, lacunar infarcts, and cognition in older Black adults.

Older Black adults are at risk of cerebral small vessel disease (CSVD), which contributes to dementia risk. Two subtypes of CSVD, arteriolosclerosis and ischemic lacunar infarcts, have been independently linked to lower cognition and higher dementia risk, but their combined effects on cognition in older Black adults are unclear. Mixed models were used to examine the associations of in vivo measures of arteriolosclerosis (ARTS) and ischemic lacunar infarcts to cognitive level and change in 370 older Black adults without dementia. RESULTS: Modeled together, higher ARTS load accounted for lower levels of global cognition, episodic memory, semantic memory, and perceptual speed, whereas higher infarct load accounted for lower levels of working memory. There were no associations with rate of cognitive change. Both arteriolosclerosis and ischemic infarcts impact the cognitive health of older Black adults, but arteriolosclerosis affects cognition more broadly and offers promise as an in vivo biomarker of dementia risk. Older Black adults are at risk of cerebral small vessel disease (CSVD) and dementia. Examined magnetic resonance imaging-derived measure of arteriolosclerosis (ARTS), infarcts, and cognition. ARTS load was widely associated with lower cognition after adjusting for infarct load. Infarct load was specifically associated with lower complex attention. More within-Black in vivo studies of CSVD subtypes and cognition are needed.

Adverse Lipid Profiles Are Associated with Lower Dementia Risk in Older People

ObjectiveMidlife dyslipidemia is associated with higher risk of dementia in late-life dementia, but the impact of late-life dyslipidemia on dementia risk is uncertain. This may be due to the large heterogeneity in cholesterol measures and study designs employed. We used detailed data from a large prospective cohort of older persons to comprehensively assess the relation between a broad range of cholesterol measures and incident dementia, addressing potential biases, confounders, and modifiers. DesignPost hoc observational analysis based on data from a dementia prevention trial (PreDIVA).Setting and participants: 3392 community-dwelling individuals, without dementia, aged 70-78 years at baseline (recruited between June 2006 and March 2009). MethodsTotal cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein A1 and B were assessed. Over a median of 6.7 years’ follow-up, dementia was established by clinical diagnosis confirmed by independent outcome adjudication. Hazard ratios (HRs) for dementia and mortality were calculated using Cox regression. ResultsDementia occurred in 231 (7%) participants. One-SD increase in LDL/HDL conveyed a 19% (P = .01) lower dementia risk and a 10% (P = .02) lower risk of dementia/mortality combined. This was independent of age, cardiovascular risk factors, cognitive function, apolipoprotein E genotype, and cholesterol-lowering drugs (CLD). This association was not influenced by the competing risk of mortality. Consistent and significant interactions suggested these associations were predominant in individuals with low body mass index (BMI) and higher education. Conclusions and implicationsDyslipidemia in older individuals was associated with a lower risk of dementia. Low BMI and higher education level mitigate poor outcomes associated with dyslipidemia. These findings suggest that a different approach may be appropriate for interpreting lipid profiles that are conventionally considered adverse in older adults. Such an approach may aid predicting dementia risk and designing intervention studies aimed at reducing dementia risk in older populations.

Shift work effects on incident neuropsychiatric disorders and shift work tolerance

BackgroundShift work is associated with susceptibility to several neuropsychiatric disorders. This study aims to investigate the effect of shift work on the incidence of neuropsychiatric disorders, and highlighting how individual variability may influence the association. MethodsUK Biobank participants with employment information were included. Cox survival was conducted in main and subgroup analyses. Correlation analyses explored the impact of shift work on brain structures, and mediation analyses were performed to elucidate the shared underlying mechanisms. Shift work tolerance was evaluated through survival analyses contrasting the risks associated with five neuropsychiatric disorders in shift versus non-shift workers across different demographic or occupational strata. ResultsThe analysis encompassed 254,646 participants. Shift work was associated with higher risk of dementia (HR 1.29, 95 % CI 1.10–1.52), anxiety (1.08, 1.01–1.15), depression (1.29, 1.22–1.36), and sleep disorders (1.18, 1.09–1.28), but not stroke (p = 0.20). Shift work was correlated with decreasing volume of various brain regions, particularly in thalamus, lateral orbitofrontal, and middle temporal. Mediation analysis revealed that increased immune response and glucose levels are common pathways linking shift work to these disorders. We observed diversity in shift work tolerance across different individual characteristics, among which socioeconomic status and length of working hours were the most essential. LimitationsSelf-reported employment information may cause misclassification and recall bias. And since we focused on the middle-aged population, the conclusions may not be representative of younger or older populations. ConclusionsOur findings indicated the need to monitor shift worker health and provide personalized management to help adapt to shift work.

Risks of Dementia in a General Japanese Older Population With Preserved Ratio Impaired Spirometry: The Hisayama Study.

Studies on the association between preserved ratio impaired spirometry (PRISm) and dementia are limited. Indeed, PRISm has often been overlooked or ignored as an index of lung function impairment. Therefore, we investigated the association of PRISm with the risk for the development of dementia in an older Japanese population. A total of 1,202 community-dwelling, older Japanese participants aged ≥65 years without dementia were followed up for a median of 5.0 years. Participants were categorized by spirometry as follows: normal spirometry (FEV1/FVC ≥0.70 and FEV1 ≥80% predicted), PRISm (≥0.70 and <80%), airflow limitation (AFL) Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 (<0.70 and ≥80%), and AFL GOLD 2 to 4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using a Cox proportional hazards model. During the follow-up period, 122 participants developed dementia. The age- and sex-adjusted incidences of dementia in the participants with normal spirometry, PRISm, AFL GOLD 1, and AFL GOLD 2 to 4 were 20.5, 37.0, 18.4, and 28.6 per 1,000 person-years, respectively. Participants with PRISm had a higher risk of dementia (HR 2.04; 95% CI, 1.19-3.49) than those with normal spirometry after adjusting for confounders. Moreover, both reduced FEV1% predicted values and FVC% predicted values were associated with the risk of dementia. PRISm was associated with an increased risk of dementia in a general older Japanese population.

The characteristic pattern of functional connectivity density influenced by postmenopausal females in the preclinical stage of dementia.

Subjective cognitive decline (SCD) is considered an early indicator of Alzheimer's disease. Previous evidence suggests that postmenopausal females are at heightened risk for developing dementia. However, the potential effects of gender (i.e. postmenopausal female) on functional connectivity density (FCD) in individuals with SCD are not well understood. A total of 56 healthy controls and 57 subjects with SCD were included. The short-range and long-range FCD (srFCD and lrFCD) mapping of each participant was calculated. The interactive effect of gender × diagnosis on the FCD was explored by two-way analysis of variance. The interaction effect of gender × diagnosis on lrFCD was primarily in the right middle frontal gyrus (MFG). The older males with SCD exhibited significantly enhanced lrFCD in the right MFG relative to other subgroups. The lrFCD of the right MFG was positively associated with cognitive performance in older females with SCD. Cognition-related functional terms were significantly related to the right MFG. Decreased lrFCD of the right MFG in cognitively normal older women may explain why postmenopausal females have a higher risk for progression to dementia than men. Furthermore, this altered pattern could be applied to identify individuals with a high risk for dementia.

Life Events and Incident Dementia: A Prospective Study of 493,787 Individuals Over 16 Years.

Life events can be stressful and have a detrimental impact on health, but evidence is inconclusive regarding life events and dementia risk. The present study tests whether life events are associated with incident dementia, whether experiencing multiple events has cumulative effects, and whether the associations vary across age, sex, race/ethnicity, socioeconomic status, and genetic vulnerability. UK Biobank participants (N = 493,787) reported on 6 life events that occurred within the past 2 years: serious illness, injury, assault to yourself or close relative, death of a spouse/partner or close relative, marital separation/divorce, and financial problems. Incident all-cause dementia was ascertained through health records from the UK National Health Service over a 16-year follow-up. Serious illness, injury, or assault to yourself, marital separation/divorce, and financial difficulties were associated with a higher risk of dementia; serious illness, injury, or assault of a close relative was associated with a lower risk of dementia. When combined, experiencing 3-4 events was associated with a more than 2-fold increase in dementia risk. The association for marital separation/divorce was stronger within the first 5 years of follow-up (consistent with reverse causality). Death of a spouse/partner or close relative was mostly unrelated to dementia risk. With few exceptions, the associations were similar across age, sex, race/ethnicity, socioeconomic status, and apolipoprotein E e4 status groups. Severe illness, injury, or personal assault, marital separation or divorce, and financial hardships may raise risk of dementia, particularly when these events occur together.

Effects of psychosocial characteristics on cognitive function in middle-aged and older adults: Focusing on change by year using the Korean Longitudinal Study of Aging panel data (2014-2018).

Old age is associated with a higher risk of dementia. Psychosocial characteristics frequently affect cognitive function; however, the exact mechanism underlying the effect of psychosocial factors on cognitive function is unclear. Therefore, this study aimed to investigate the effects of psychosocial characteristics on cognitive function. The participants comprised 4809 middle-aged and older (years 50+) adults. The analysis used data from the Korean Longitudinal Study of Aging from 2014 to 2018. The effects of neighborhood interaction, depression, life satisfaction, and economic activity on cognitive function were examined, and a linear mixed model analysis was performed to assess the change in cognitive function by year. A statistically significant association was found between neighborhood interaction and time. Additionally, cognitive function decreased in the presence of depression and with time. In men, significant interactions were found between depression and time and between economic activity and time. In women, significant interactions were found between life satisfaction and time. The findings indicate that since active neighborhood interaction positively affects cognitive function, it is necessary to develop various community-wide social activity programs for middle-aged and older adults. As depression is a risk factor for cognitive impairment, it is crucial to prevent cognitive decline through continuous management of depression. Given the positive effects of economic activity on cognitive function in men, it is essential to expand infrastructure to sustain economic activity by developing educational programs and creating job opportunities for middle-aged and older men.

Sleep Disorders and Dementia Risk in Older Patients with Kidney Failure: A Retrospective Cohort Study.

Community-dwelling older adults with sleep disorders are at higher risk of developing dementia. Greater than 50% of older patients with kidney failure experience sleep disorders, which may explain their high burden of dementia. Among 216,158 patients (age ≥66 years) with kidney failure (United States Renal Data System; 2008-2019), we estimated the risk of dementia (including subtypes) associated with sleep disorders using Cox proportional-hazard models with propensity score weighting. We tested whether positive airway pressure (PAP) therapy was associated with reduced dementia risk among patients with obstructive sleep apnea (OSA). 26.3% of patients were diagnosed with sleep disorders; these patients had a higher five-year unadjusted cumulative incidence for any type of dementia (36.2% vs. 32.3%; P<0.001), vascular dementia (4.4% vs. 3.7%; P<0.001), and other/mixed dementia (29.3% vs. 25.8%; P<0.001). Higher risk of any type of dementia was identified in patients with insomnia (aHR=1.42; 95%CI: 1.34-1.51), sleep-related breathing disorders (SRBDs) (aHR=1.20; 95%CI: 1.17-1.23), and other sleep disorders (aHR=1.24; 95%CI: 1.11-1.39). Higher vascular dementia risk was observed in patients with insomnia (aHR=1.43; 95%CI: 1.19-1.73), SRBDs (aHR=1.15; 95%CI: 1.07-1.24). Patients with SRBDs (aHR=1.07; 95%CI: 1.00-1.15) were at higher risk of Alzheimer's disease. Among patients with OSA, PAP therapy was associated with lower risk for any type of dementia (aHR=0.82; 95%CI: 0.76-0.90), and vascular dementia (aHR=0.65; 95%CI: 0.50-0.85). Older patients with kidney failure and sleep disorders are at a higher risk of dementia. Sleep is an important modifiable factor that should be considered for targeted interventions to mitigate dementia risk in patients with kidney failure. For patients with OSA, PAP therapy is associated with lower dementia risk.

Association of infertility and recurrent pregnancy loss with the risk of dementia

Emerging evidence has shown the association between female reproductive histories (e.g., menarche age, parity, premature and early menopause) and the risk of dementia. However, little attention has been given to infertility and pregnancy loss. To examine the associations of infertility, recurrent miscarriages, and stillbirth with the risk of dementia, this study used data from four cohorts in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. Women with data on at least one of the reproductive exposures of interest, dementia, and all covariates were included. Histories of infertility, miscarriage, and stillbirth were self-reported. Dementia (including Alzheimer’s disease) was identified through surveys, aged care, pharmaceutical, hospital, and death registry data. Cause-specific Cox regression models were used to estimate the hazard ratios of dementia, accounting for well-established risk factors of dementia, study variability, and within-study correlation. Overall, 291,055 women were included at a median (interquartile range) age of 55.0 (47.0–62.0) at baseline. During the median (interquartile range) follow-up period of 13.0 (12.0–14.0) years, 3334 (1.2%) women developed dementia. Compared to women without stillbirth, a history of recurrent stillbirths (≥ 2) was associated with 64% higher risk of dementia (adjusted hazard ratio = 1.64, 95% confidence interval: 1.46–1.85). Compared to women without miscarriage, women with recurrent miscarriages (≥ 3) were at 22% higher risk of dementia (adjusted hazard ratio = 1.22, 95% confidence interval: 1.19–1.25). These findings suggest that recurrent stillbirths is a risk factor for dementia and may need to be considered in risk assessment of dementia in women.

Gender-specific analysis of social connection patterns and risk of dementia in community-dwelling older people.

Poor social connection is considered a risk factor for dementia. Since socializing behaviors may cluster together or act compensatorily, we aimed to investigate social connection patterns and their association with dementia, for men and women separately. A total of 12,896 community-dwelling older adults (mean±SD age: 75.2±4.3 years, 54% women) without major cognitive impairment were included. Latent class analysis was conducted using 24 baseline social connection indicators. Cox proportional hazards regression was used to estimate the association between latent classes and incident dementia over 12 (median: 8.4) years follow-up. Three distinct classes were identified in both genders: strong social connections with an intermediate friend-relative network (Class 1: men, 43.8%; women, 37.9%), weak social connections (Class 2: men, 29.6%; women, 27.4%), and strong social connections with a larger friend-relative network (Class 3: men, 26.6%; women, 34.7%). Compared to Class 1, men in Class 2 (HR: 1.38, 95% CI: 1.08-1.77) and women in Class 3 (HR: 1.27, 95% CI: 1.01-1.60) had an increased risk of dementia. Dementia risk varies with different social connection patterns among older men and women. Three distinct social connection patterns were identified based on 24 indicators. These patterns were related to dementia risk differently in men and women. In men, a weak social connection pattern was associated with a higher dementia risk. In women, a strong social connection with a relatively larger friend-relative network was associated with a greater dementia risk.

Concurrent nutrient deficiencies are associated with dementia incidence.

While observational research suggests a protective role for nutrition in brain aging, intervention studies remain inconclusive. This failing translation from observational to interventional research may result from overlooking nutrient interactions. We developed a nutrient status index capturing the number of suboptimal statuses of omega-3 fatty acids, homocysteine, and vitamin D (range 0 to 3). We associated this index with dementia incidence in a subsample (age ≥ 50 years) of the Framingham Heart Study Offspring cohort. Among 968 participants, 79 developed dementia over 15.5 years (median follow-up). Each point increase in nutrient status index was associated with a 50% higher risk of dementia (hazard ratio [HR]=1.50; 95% confidence interval [CI]=1.16, 1.96). Participants with three high-risk statuses had a four-fold increased risk of dementia compared to participants without high-risk status (HR=4.68; 95% CI=1.69, 12.94). Concurrent nutrient deficiencies are associated with the risk of dementia. The potential of optimizing nutritional status to lower dementia risk warrants further study. Nutrition and dementia research calls for multiple-nutrient approaches. We studied combined suboptimal statuses of omega-3 polyunsaturated fatty acids, homocysteine, and vitamin D. Suboptimal status of the three nutrients was associated with dementia risk. The risk estimate was larger than for other factors (ie, diabetes, apolipoprotein Eε4 carrier). Future studies should assess the effect of improving nutrient status on dementia risk.

Incidence of Dementia Before Age 65 Years Among World Trade Center Attack Responders

Reports suggest that the individuals who served in rescue operations following the terrorist attacks on the World Trade Center (WTC) have poorer brain health than expected. To assess the incidence of dementia before age 65 years in a prospective study of WTC responders and to compare incidence among responders with severe exposures to debris vs responders not exposed to building debris or who wore personalized protective equipment (PPE). This prospective cohort study was conducted from November 1, 2014, to January 1, 2023, in an academic medical monitoring program available to verified WTC responders residing on Long Island, New York. Responders 60 years of age or younger without dementia at the time of their first cognitive assessment were followed up every 18 months, on average, for up to 5 years. Exposure severity was based on responses to a detailed questionnaire of WTC exposures and exposure-related activities that included exposures to fine particulate dust and potentially neurotoxic debris, duration of work, and the use of PPE. Exposure level was divided into 5 categories ranging from low to severe. Incidence of all-cause dementia before age 65 years was the primary outcome. Dementia was diagnosed following standard guidelines relying on repeated measures of cognition. Of 9891 responders, 5010 were eligible for inclusion in this study of cognitive function (median [IQR] age, 53 [48-57] years; 4573 [91.3%] male). There were 228 cases of dementia identified during 15 913.1 person-years of follow-up. Increasing WTC exposure severity was associated with incremental increases in the incidence rate of dementia per 1000 person-years (low, 2.95 [95% CI, 1.07-11.18]; mild, 12.16 [95% CI, 10.09-14.79]; moderate, 16.53 [95% CI, 13.30-20.81]; high, 30.09 [95% CI, 21.35-43.79]; and severe, 42.37 [95% CI, 24.86-78.24]). Adjusting for social, demographic, and relevant medical factors, each unit increase in exposure severity was associated with increased incidence of dementia (adjusted hazard ratio, 1.42 [95% CI, 1.18-1.71]; P < .001; mean risk difference, 9.74 [95% CI, 2.94-32.32] per 1000 person-years; P < .001). In this cohort study of WTC responders who survived these unique exposures and participated in a longitudinal follow-up study of cognition from 2014 through 2022, when compared with responders with the lowest exposure levels or responders who used PPE, more severe exposure to dust or debris was significantly associated with a higher risk of dementia before 65 years of age. This study suggests that the reliable use of PPE might help prevent the onset of dementia before age 65 years among individuals exposed to an uncontrolled building collapse. Future research is warranted to determine cerebral biomarkers for individuals with exposure-associated dementia.

What's New in Dementia Risk Prediction Modelling? An Updated Systematic Review.

Identifying individuals at high risk of dementia is critical to optimized clinical care, formulating effective preventative strategies, and determining eligibility for clinical trials. Since our previous systematic reviews in 2010 and 2015, there has been a surge in dementia risk prediction modelling. The aim of this study was to update our previous reviews to explore, and critically review, new developments in dementia risk modelling. MEDLINE, Embase, Scopus, and Web of Science were searched from March 2014 to June 2022. Studies were included if they were population- or community-based cohorts (including electronic health record data), had developed a model for predicting late-life incident dementia, and included model performance indices such as discrimination, calibration, or external validation. In total, 9,209 articles were identified from the electronic search, of which 74 met the inclusion criteria. We found a substantial increase in the number of new models published from 2014 (>50 new models), including an increase in the number of models developed using machine learning. Over 450 unique predictor (component) variables have been tested. Nineteen studies (26%) undertook external validation of newly developed or existing models, with mixed results. For the first time, models have also been developed in low- and middle-income countries (LMICs) and others validated in racial and ethnic minority groups. The literature on dementia risk prediction modelling is rapidly evolving with new analytical developments and testing in LMICs. However, it is still challenging to make recommendations about which one model is the most suitable for routine use in a clinical setting. There is an urgent need to develop a suitable, robust, validated risk prediction model in the general population that can be widely implemented in clinical practice to improve dementia prevention.

Bipolar disorder and Lewy body dementia: case report and literature review.

Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in which depressive and psychotic symptoms commonly coexist. In contrast, psychotic symptoms occur more frequently in depressive episodes of bipolar disorder (BD) than in major depressive disorder (MDD). Although MDD is a significant risk factor for dementia, studies exploring the relationship between BD and dementia are lacking. This report details the case of a 74-year-old female who experienced severe psychotic depression that led to suicide attempts during a long-term course of young-onset BD. Ultimately, she was diagnosed with DLB based on her neurocognitive symptoms and results of the neuroimaging examination. She had experienced multiple relapses in the past, predominantly characterized by depressive episodes in her old age. Notably, she had never undergone lithium treatment, which is known for its potential efficacy in preventing relapse and dementia. Recent systematic reviews and meta-analyses have suggested that patients with BD have a higher risk of dementia than the general population, and that lithium usage is associated with a reduced risk. Moreover, patients with BD have been suggested to have an elevated risk of developing Parkinson's disease (PD), and the pathophysiological relationship between BD and PD may be attributed to dopamine dysregulation resulting from multiple relapses. Future research is imperative to identify strategies for preventing dementia in patients with BD and to develop interventions for the comorbidities of BD and DLB.