Higher Risk Of Dementia Research Articles

Age at diagnosis of diabetes, obesity, and the risk of dementia among adult patients with type 2 diabetes.

While Type 2 Diabetes Mellitus (T2DM) prevalence is increasing among younger individuals, few studies have examined how age at T2DM diagnosis relates to dementia risk in diabetic populations. We aimed to investigate the association between age at T2DM diagnosis and subsequent dementia risk, and to determine whether obesity moderates this relationship. We conducted a prospective cohort study using data from the Health and Retirement Study (2002-2016) matched with its 2003 Diabetes Mail-Out Survey. The study included 1,213 dementia-free adults aged ≥50 with diagnosed T2DM. Primary exposures were age at T2DM diagnosis (categorized as <50, 50-59, 60-69, and ≥70 years) and obesity status (BMI ≥30 kg/m2). The outcome was incident dementia, assessed using the Telephone Interview for Cognitive Status. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic factors, health behaviors, health status, and diabetes medication use. Over a median follow-up of 10 (interquartile range, 6-14) years, 216 (17.8%) participants developed dementia. Compared to participants diagnosed with T2DM at age ≥70 years, those diagnosed at younger ages had increased dementia risk: HR 1.70 (95% CI, 1.03-2.80) for 60-69 years, 1.72 (95% CI, 1.06-2.79) for 50-59 years, and 1.90 (95% CI, 1.14-3.18) for <50 years. Obesity significantly moderated this relationship, with obese individuals diagnosed with T2DM before age 50 showing the highest dementia risk (HR 3.05; 95% CI 1.23-7.56) compared to non-obese individuals diagnosed at ≥50 years. Younger age at diagnosis of T2DM was significantly associated with a higher risk of dementia, particularly among individuals with obesity. Interventions specifically targeting obesity may be more effective in preventing dementia for adults with a younger onset of T2DM.

Abstract 4136600: Hypertensive disorders of pregnancy and the risk of Dementia, Alzheimer’s disease, and Vascular Dementia. A Systematic review and Meta-analysis of 25,03,538 women participants.

Background: Hypertensive disorders of pregnancy (HDP) are associated with maternal adverse cardiovascular outcomes. However, their association with maternal Dementia and Alzheimer’s disease is not well established with limited and conflicting results to date. Objective: We sought to evaluate the association between HDP and risk of incidence of Dementia, and Alzheimer’s disease. Methods: We performed a systematic review and meta-analysis of available literature that enrolled women with HDP and women without HDP groups. PubMed, Embase and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 8 studies with 2503538 patients (1,51,905 in women with HDP and 23,51,633 in the women without HDP group) were included. Pooled analysis shows that HDP women were having 37% higher risk of dementia (aHR, 1.37(95%CI: 1.27-1.46), P&lt;0.001, I2=0%) when compared with women without HDP. Further pooled analysis showed that women with HDP were having 28% higher risk of Alzheimer’s disease (aHR, 1.28(95%CI: 1.56), P&lt;0.001, I2=53.98%), and 2-fold higher risk of vascular dementia (aHR, 2.49(95%CI: 1.29-3.68), P&lt;0.001, I2=71.51%) when compared with women without HDP. Conclusion: Women with HDP were at higher risk of developing Dementia, and Alzheimer's disease in future.

Modifiable dementia risk associated with smaller white matter volume and altered 1/f aperiodic brain activity: cross-sectional insights from the LEISURE study.

The rising prevalence of dementia necessitates identifying early neurobiological markers of dementia risk. Reduced cerebral white matter volume and flattening of the slope of the electrophysiological 1/f spectral power distribution provide neurobiological markers of brain ageing alongside cognitive decline. However, their association with modifiable dementia risk remains to be understood. A cross-sectional sample of 98 healthy older adults (79 females, mean age = 65.44) underwent structural magnetic resonance imaging (sMRI), resting-state electroencephalography (EEG), cognitive assessments and dementia risk scoring using the CogDrisk framework. Univariate and multivariate linear regression models were conducted to investigate the relationships between modifiable dementia risk and sMRI brain volumes, the exponent of EEG 1/f spectral power, and cognition, whilst controlling for non-modifiable factors. Smaller global white matter volume (F(1,87) = 6.884, R2 = 0.073, P = .010), and not grey (F(1,87) = 0.540, R2 = 0.006, P = .468) or ventricle volume (F(1,87) = 0.087, R2 = 0.001, P = .769), was associated with higher modifiable dementia risk. A lower exponent, reflecting a flatter 1/f spectral power distribution, was associated with higher dementia risk at frontal (F(1,92) = 4.096, R2 = 0.043, P = .046) but not temporal regions. No significant associations were found between cognitive performance and dementia risk. In multivariate analyses, both white matter volume and the exponent of the 1/f spectral power distribution independently associated with dementia risk. Structural and functional neurobiological markers of early brain ageing, but not cognitive function, are independently associated with modifiable dementia risk in healthy older adults.

Joint effect of polysocial risk score, lifestyle and genetic susceptibility with the risk of dementia: A prospective cohort study

ObjectivesThe comprehensive impact of polysocial risk score (PsRS)—encompassing multiple social determinants of health (SDoHs) with genetic and lifestyle factors on dementia incidence remains to be elucidated. Study designThis study aimed to clear the associations between PsRS and dementia incidence and evaluated how genetic and lifestyle factors modified these associations in the UK Biobank cohort.Methods: The detailed prospective study involved over 500,000 participants when recruited in 2006–2010. The PsRS was calculated by 12 SDoHs across psychosocial factors, socioeconomic status, and neighborhood and living environment. A healthy lifestyle score was constructed from physical activities, alcohol consumption, smoking status, and diet. A genetic risk score (GRS) was computed via genotype data from UK Biobank. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between PsRS, lifestyle factors, GRS and dementia. ResultsResults showed the participants with intermediate (HR = 1.32, 95%CI: 1.20–1.45) and high PsRS (HR = 2.10, 95 % CI: 1.91–2.32) were significantly associated with an increased risk of dementia compared with those with a low PsRS. Then, compared with participants with low PsRS and favorable lifestyle/low GRS, high PsRS and unfavorable lifestyle/high GRS had the highest risk of dementia (HR = 3.11,95%CI: 2.63–3.68)/(HR = 3.56, 95%CI: 2.62–4.85). ConclusionsBoth high PsRS and GRS were significantly associated with higher dementia risk. A favorable lifestyle could reduce dementia incidence regardless of high PsRS or GRS. Additionally, focusing on the intervention of SDoHs would be positive in preventing dementia.

Sarcopenia and associated factors among older adults at high risk of dementia

Abstract Background Sarcopenia and dementia share pathophysiological pathways and risk factors, including advanced age, physical inactivity, unhealthy diet, smoking and diabetes. Older adults at high risk of dementia may face increased susceptibility to sarcopenia, which can also exacerbate cognitive decline. Thus, this study aims to estimate the frequency of sarcopenia and its associated factors within this vulnerable population. Methods This cross-sectional analysis includes data from a subset of older adults (≥65 years of age) enrolled in the MIND-Matosinhos randomized controlled trial, a community-based cognitive decline prevention program. Per the European Working Group on Sarcopenia in Older People, probable sarcopenia is defined as low muscle strength (handgrip strength &amp;lt;16 kg for women and &amp;lt;27 kg for men). Sociodemographic, lifestyle and health-related data were collected via structured questionnaires. To assess factors associated with sarcopenia, odds ratios (OR) and respective confidence intervals (95% CI) were estimated using logistic regression. Results A total of 157 participants (58.6% female), with a median age of 73 years (range: 65 to 85 years), were included. The overall prevalence of sarcopenia was 21.7% (n = 34). After adjusting for sex, age and education, inadequate adherence to Mediterranean Diet (MD) (OR = 10.90; 95% CI:1.41-84.52), current smoking status (OR = 5.06; 95% CI:1.06-24.18) and poorer self-perceived health (OR = 2.74; 95% CI:1.03-7.28) were positively associated with sarcopenia. No other statistically significant associations were found. Conclusions The observed sarcopenia frequency underscores the need for enhanced screening and management of this condition in community settings and among those at dementia risk. Inadequate adherence to MD, smoking and poor self-perceived health, seem to be associated with sarcopenia in older adults at high risk of dementia. Sarcopenia prevention should involve a holistic approach to promoting a healthy lifestyle. Key messages • Sarcopenia was observed in 21.7% of older adults at high risk of dementia, indicating a significant burden on this vulnerable population. • Inadequate adherence to the Mediterranean diet, smoking and poor self-perceived health were associated with sarcopenia.

Neurophysiological markers of early cognitive decline in older adults: a mini-review of electroencephalography studies for precursors of dementia.

The early detection of cognitive decline in older adults is crucial for preventing dementia. This mini-review focuses on electroencephalography (EEG) markers of early dementia-related precursors, including subjective cognitive decline, subjective memory complaints, and cognitive frailty. We present recent findings from EEG analyses identifying high dementia risk in older adults, with an emphasis on conditions that precede mild cognitive impairment. We also cover event-related potentials, quantitative EEG markers, microstate analysis, and functional connectivity approaches. Moreover, we discuss the potential of these neurophysiological markers for the early detection of cognitive decline as well as their correlations with related biomarkers. The integration of EEG data with advanced artificial intelligence technologies also shows promise for predicting the trajectory of cognitive decline in neurodegenerative disorders. Although challenges remain in its standardization and clinical application, EEG-based approaches offer non-invasive, cost-effective methods for identifying individuals at risk of dementia, which may enable earlier interventions and personalized treatment strategies.

Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study.

Accelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults. This study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA. Nested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age. Small sample size limited estimate precision, however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.

Socioeconomic inequalities in dementia risk among a population-based cohort: Quantifying the role of a broad combination of lifestyle factors.

The complex associations of socioeconomic status (SES) and lifestyle with dementia are unclear. Our objective was to examine whether a broad combination of lifestyle factors mediates the associations of SES with incident dementia and the extent of interaction or joint relations of lifestyles and SES with dementia. A total of 274,871 participants from the UK Biobank were included. SES was assessed using the Townsend Deprivation Index. A lifestyle index was created based on smoking status, alcohol consumption, physical activity, social connections, sleep duration, diet, and sedentary behavior. Cox proportional hazards models were fitted. Mediation and interaction analyses were conducted to explore the relationship between lifestyles and SES in dementia. The HRs (95% CIs) for when participants with low SES were compared with participants of high SES were 1.32 (1.22-1.42) for all-cause dementia, 1.25 (1.11-1.40) for Alzheimer's disease (AD), and 1.61 (1.37-1.90) for vascular dementia (VD). Lifestyles explained ≤ 7.8% of socioeconomic disparities in dementia. Unhealthy lifestyle categories were associated with a higher risk of dementia and its subtypes across all SES levels. The HRs (95% CIs) for all-cause dementia, AD, and VD comparing participants with low SES and the least healthy lifestyle versus those with high SES and the healthiest lifestyle were 1.82 (1.56-2.11), 1.51 (1.20-1.90), and 2.56 (1.81-3.61), respectively. Adhering to a healthy lifestyle may prevent dementia across all socioeconomic groups, but socioeconomic inequalities in dementia cannot be fully addressed by promoting healthy lifestyles alone. The social determinants of dementia need to be better addressed.

Effects of depression and cognitive impairment on increased risks of incident dementia: a prospective study from three elderly cohorts

Depression is usually accompanied with cognitive impairment and increases risk of incident dementia. However, evidence has been limited on the effect size of depression with cognitive impairment and their synergistic effect on future dementia. To explore this, we examined three large cross-country population-based prospective cohorts. Depressive symptoms were assessed by epidemiologic scale, while cognitive impairment was defined by subjective cognitive tests. Dementia was ascertained by self-reported physician-diagnosed conditions. Cox proportional hazard models were employed to determine the hazard ratio (HR) and 95% confidence interval (95% CI), with adjustments of potential confounding variables. Addictive and multiplicative interactions were calculated to evaluate the synergistic effect. A total of 64,706 participants were included at baseline (mean age: 63.9, female: 55.2%), where 4197 (6.5%) individuals had depressive symptoms only, 28,175 (43.5%) individuals had cognitive impairment only, 11,564 (17.9%) individuals had both, and 20,770 (32.1%) individuals had neither. Compared with the neither group, all the other three groups had higher risks of subsequent dementia (depression only: HR 1.65, 95% CI 1.26–2.17; cognitive impairment only: HR 2.71, 95% CI 2.33–3.14; depression with cognitive impairment: HR 3.51, 95% CI 2.95–4.17). There was insignificant additive (RERI, 0.15, 95% CI −0.45–0.75; AP, 0.042, 95% CI −0.13–0.21; SI, 1.06, 95% CI 0.83–1.37) and multiplicative (0.78, 95% CI 0.58–1.06) interaction between depression and cognitive impairment on subsequent dementia. We found depression with cognitive impairment has higher risks of dementia than either condition alone and no significant synergistic effect exists between these two factors.

Validation of the Updated "LIfestyle for BRAin health" (LIBRA) Index in the English Longitudinal Study of Ageing and Maastricht Aging Study.

The "LIfestyle for BRAin health" (LIBRA) index was recently updated with three new modifiable factors: hearing impairment, social contact, and sleep (LIBRA2), but has not yet been validated. Comparison of the performance of both LIBRA versions in predicting dementia risk. Longitudinal data from the English Longitudinal Study of Ageing (ELSA) and the Maastricht Aging Study (MAAS) were used. The weighted LIBRA (11/12 factors available) and LIBRA2 (14/15 factors available) scores were calculated, with higher scores representing an unhealthier lifestyle. Dementia diagnoses were based on self- or informant reported physician diagnosis, an informant-based cognitive screening tool, registry data or test data. Cox-proportional hazards regression was used to investigate the association between LIBRA(2) scores and dementia risk. Model fit and predictive accuracy were determined using the Akaike information criterion and Harrell's C index. Over an average follow-up of 8.3 years in ELSA and 17.9 years in MAAS, 346 (4.6%) and 120 (8.5%) individuals developed dementia, respectively. In ELSA, a one-point increase in LIBRA2 was associated with an 8% (1.06-1.11) higher dementia risk (LIBRA: 13%, 1.09-1.16). In MAAS, a one-point increase in LIBRA2 was associated with a 6% (1.01-1.12) higher dementia risk (LIBRA: 8%, 0.99-1.16). In ELSA, LIBRA (Harrell's C = 0.68) and LIBRA2 (Harrell's C = 0.67) performed similarly. In MAAS, LIBRA2 (Harrell's C = 0.62) performed better compared to LIBRA (Harrell's C = 0.52). LIBRA2 is a better model for identifying individuals at increased dementia risk and for public health initiatives aimed at dementia risk reduction.

Associations of combined accelerated biological aging and genetic susceptibility with incident dementia: a prospective study in the UK Biobank

BackgroundAccelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease.MethodsWe included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales.ResultsThese findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale.ConclusionsAccelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.

Effects of Occupational and Leisure-Time Physical Activity on the Risk of Dementia: Results From the Copenhagen City Heart Study.

Leisure-time physical activity (LTPA) decreases the risk of dementia, whereas occupational physical activity (OPA) possibly increases the risk. Yet, previous findings are mixed. We therefore aimed to investigate the effect of LTPA and OPA, respectively, on dementia among men and women. In this observational, longitudinal study, we used data from the second wave of a population-based cohort from the municipality of Copenhagen as baseline. Data were collected in 1981-1983, and 10 343 participants were followed until the end of 2016. LTPA and OPA were self-reported, and information on dementia diagnoses and redemption of dementia medication was obtained at an individual level from national health registers. We used Poisson regression to analyze the association between LTPA/OPA and dementia and adjusted for self-reported age, socioeconomic factors, stress, and cardiovascular risk factors (smoking, alcohol, body mass index, and blood pressure). A higher level of LTPA was associated with a lower dementia risk among men, but we found no clear association among women. OPA and dementia were not associated among men, but occupationally active women who reported OPA in terms of walking, lifting, and heavy work had a higher risk of dementia than women with sedentary jobs. This study supported earlier findings of a protective effect of LTPA on dementia among men. Women in physically demanding jobs possibly have a higher risk of dementia, yet this finding warrants further investigation in future studies.

Increased Systemic Immune-Inflammation Index as a Novel Indicator of Alzheimer's Disease Severity.

Inflammatory processes and neurodegeneration are common features of Alzheimer's disease (AD). The systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are easily accessible, cost-effective prognostic indicators of inflammation status. We assessed the diagnostic value of SII and compared the efficacies of NLR, PLR, and SII in predicting AD severity. Between January 2021 and December 2022, this prospective, cross-sectional clinical study included 175 patients with AD and 61 controls. SII, NLR, and PLR were calculated. Age, white blood cell and lymphocyte counts, and NLR and PLR values were significantly different between the patient and control groups (P <.05). Age, hemoglobin, neutrophil, NLR, and SII values were significantly different among dementia severity subgroups (P <.05). Compared with PLR and SII, NLR was more strongly correlated with dementia severity. In the analysis of adjusted data by gender, it was found that hemoglobin level is significantly negatively associated with dementia severity in males, while in females, age and PLR are significantly positively associated with dementia severity, and lymphocyte count and SII are negatively associated. SII, a novel inflammatory marker, was associated with dementia severity in patients with AD. Compared with PLR and SII, NLR was more strongly correlated with dementia severity. In future studies with larger populations, SII and NLR values can be used to determine dementia severity and establish follow-up plans for patients with high dementia risk.

Exploring first-degree family history in a cohort of Portuguese Alzheimer’s disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors

BackgroundAlzheimer’s disease (AD) heritability is estimated to be around 70–80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD.ObjectiveIn this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients.MethodsWe collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents’ birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes.ResultsWe included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau.ConclusionsOur study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.

Social relationship factors, depressive symptoms, and incident dementia: a prospective cohort study into their interrelatedness.

Different aspects of social relationships (e.g., social network size or loneliness) have been associated with dementia risk, while their overlap and potentially underlying pathways remain largely unexplored. This study therefore aimed to (1) discriminate between different facets of social relationships by means of factor analysis, (2) examine their associations with dementia risk, and (3) assess mediation by depressive symptoms. Thirty-six items from questionnaires on social relationships administered in Wave 2 (2004/2005) of the English Longitudinal Study of Ageing (n = 7536) were used for exploratory and confirmatory factor analysis. Factors were then used as predictors in Cox proportional hazard models with dementia until Wave 9 as outcome, adjusted for demographics and cardiovascular risk factors. Structural equation modeling tested mediation by depressive symptoms through effect decomposition. Factor analyses identified six social factors. Across a median follow-up time of 11.8 years (IQR = 5.9-13.9 years), 501 people developed dementia. Higher factor scores for frequency and quality of contact with children (HR = 0.88; p = 0.021) and more frequent social activity engagement (HR = 0.84; p < 0.001) were associated with lower dementia risk. Likewise, higher factor scores for loneliness (HR = 1.13; p = 0.011) and negative experiences of social support (HR = 1.10; p = 0.047) were associated with higher dementia risk. Mediation analyses showed a significant partial effect mediation by depressive symptoms for all four factors. Additional analyses provided little evidence for reverse causation. Frequency and quality of social contacts, social activity engagement, and feelings of loneliness are associated with dementia risk and might be suitable targets for dementia prevention programs, partly by lowering depressive symptoms.

Clinical implications of head trauma in frontotemporal dementia and primary progressive aphasia

BackgroundTraumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.MethodsWe studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).ResultsYears of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).ConclusionsLifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

The Associations of Sensory Impairment With 10-Year Risk of Dementia and Alzheimer's Disease: The Health and Retirement Study, 2010-2020.

Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings. To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50. A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. Participants were categorized as having no visual or hearing impairment, visual impairment only, hearing impairment only, and dual sensory impairment. Fine-Gray competing risk regression model was applied to estimate the associations of sensory impairment with incident dementia and Alzheimer's disease, adjusted for demographic characteristics, health behaviors, and health conditions at baseline. Of 20,248 identified individuals, 14.6% had visual impairment only, 11.2% had hearing impairment only, and 9.1% had dual impairment at baseline. After adjusting for all covariates, dual sensory impairment was associated with higher risk of dementia (HR = 1.46, 95% CI: 1.23-1.73) and Alzheimer's disease (HR = 1.35, 95% CI: 1.03-1.76). Visual impairment only was also associated with incident dementia and Alzheimer's disease among individuals <65 years. Older adults in the U.S. with visual and hearing impairments simultaneously had a particularly greater risk of dementia and Alzheimer's disease, indicating the needs of targeted screening for timely treatment and further prevention of dementia and Alzheimer's disease.

Randomised controlled decentralised feasibility trial of a fixed low-dose combination antihypertensive drug strategy to attenuate cognitive decline in high-risk adults

ObjectivesThe Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures...

Potential for reducing dementia risk: association of the CAIDE score with additional lifestyle components from the LIBRA score in a population at high risk of dementia

Objectives Various dementia risk scores exist that assess different factors. We investigated the association between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score and modifiable risk factors in the Lifestyle for Brain Health (LIBRA) score in a German population at high risk of Alzheimer’s disease. Method Baseline data of 807 participants of AgeWell.de (mean age: 68.8 years (SD = 4.9)) were analysed. Stepwise multivariable regression was used to examine the association between the CAIDE score and additional risk factors of the LIBRA score. Additionally, we examined the association between dementia risk models and cognitive performance, as measured by the Montreal Cognitive Assessment. Results High cognitive activity (β = −0.016, p < 0.001) and high fruit and vegetable intake (β = −0.032, p < 0.001) correlated with lower CAIDE scores, while diabetes was associated with higher CAIDE scores (β = 0.191; p = 0.032). Although all were classified as high risk on CAIDE, 31.5% scored ≤0 points on LIBRA, indicating a lower risk of dementia. Higher CAIDE and LIBRA scores were associated with lower cognitive performance. Conclusion Regular cognitive activities and increased fruit and vegetable intake were associated with lower CAIDE scores. Different participants are classified as being at-risk based on the dementia risk score used.

Significance of plasma p-tau217 in predicting long-term dementia risk in older community residents: Insights from machine learning approaches.

Whether plasma biomarkers play roles in predicting incident dementia among the general population is worth exploring. A total of 1857 baseline dementia-free older adults with follow-ups up to 13.5 years were included from a community-based cohort. The Recursive Feature Elimination (RFE) algorithm aided in feature selection from 90 candidate predictors to construct logistic regression, naive Bayes, bagged trees, and random forest models. Area under the curve (AUC) was used to assess the model performance for predicting incident dementia. During the follow-up of 12,716 person-years, 207 participants developed dementia. Four predictive models, incorporated plasma p-tau217, age, and scores of MMSE, STICK, and AVLT, exhibited AUCs ranging from 0.79 to 0.96 in testing datasets. These models maintained robustness across various subgroups and sensitivity analyses. Plasma p-tau217 outperforms most traditional variables and may be used to preliminarilyscreen older individuals at high risk of dementia. Plasma p-tau217 showed comparable importance with age and cognitive tests in predicting incident dementia among community older adults. Machine learning models combining plasma p-tau217, age, and cognitive tests exhibited excellent performance in predicting incident dementia. The training models demonstrated robustness in subgroup and sensitivity analysis.