Increased Risk Of Dementia Research Articles

Genetic risk factors underlying white matter hyperintensities and cortical atrophy

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical ‘atrophy’ identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical ‘atrophy’ showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. 15 of the 20 loci regulated the expression of 54 genes in the cerebral cortex that, together with their co-expressed genes, were enriched in biological processes of axonal cytoskeleton and intracellular transport. The white matter hyperintensities-cortical thickness associations were most pronounced in cortical regions with higher expression of genes specific to excitatory neurons with long-range axons traversing through the white matter. The meta-GWAS-based polygenic risk score predicts vascular and all-cause dementia in an independent sample of 500,348 individuals. Thus, the genetics of white matter hyperintensities-related cortical atrophy involves vascular and neuronal processes and increases dementia risk.

Chronic pain-induced methylation in the prefrontal cortex targets gene networks associated with cognition and Alzheimer’s disease

Chronic pain is prevalent among aging adults. Epidemiologic evidence has demonstrated that individuals with chronic pain have accelerated memory decline and increased probability of dementia. Neurophysiologic, molecular, and pharmacologic hypotheses have been proposed to explain the relationship between chronic pain and cognitive decline, but there remains currently limited evidence supporting any of these. Here, we integrate multi-omic data across human cohorts and rodent species and demonstrate that methylation in the prefrontal cortex induced by chronic pain specifically targets transcriptional networks associated with cognitive ability, memory, and Alzheimer’s disease in humans. We validate this with multiple independent data sets and identify cortical microglia as a likely mechanism by which chronic pain can increase dementia risk. Our analyses support the molecular hypothesis for the role of chronic pain in cognitive decline and identifies several potential therapeutic targets.

Increased dementia risk in patients with Parkinson's disease attributed to metabolic syndrome.

Metabolic syndrome (MetS) manifests resembling pathophysiological mechanisms with Parkinson's disease (PD). Current research on the overall population has emphasized MetS as a freestanding risk factor for cognition. This research aims to explore the impact of MetS on cognition in Parkinson's patients. We involved subjects identified as having early-stage PD patients. The MetS was diagnosed dependent on parameters overviewed in the National Cholesterol Education Program's Adult Treatment Panel III. The clinical severity and stages in patients with PD were dependent on the disease rating scales. The cognition was evaluated by the Turkısh version of the Montreal Cognitive Assessment Scale (MoCA-TR). The cases were categorized according to cognitive failure: mild cognitive impairment in PD (PD-MCI), and PD dementia (PDD). Metabolic syndrome was present in 39.6% of the participants. 22.0% of patients were in the normal cognition, 29.1% in the PD-MCI group, and 48.9% in the PD-D group. The cognitive scores in patients with MetS is considerably lower than MetS negative group. A statistically notable inverse association was detected between fasting blood glucose levels and the visual-spatial/executive functions, naming, language, and orientation scores. The multivariate logistic regression analysis showed individuals with MetS were found to have an 11.308 times higher risk of PD-D (odds ratio [OR]: 11,3, 95% confidence interval [CI]: 1.61-79.2 ). We discerned the occurrence of MetS in PD raises the possibility of advancing dementia. This suggests that considering MetS in this patient group could contribute to the effective management of dementia.

Longitudinal Changes in Peak Expiratory Flow Predict Risk for Incident Dementia.

Impaired respiratory function, measured via peak expiratory flow (PEF), has been associated with increased dementia risk. However, much of the current literature uses cross-sectional measures of PEF, whereas longitudinal relationships between changes in respiratory function and dementia risk are underexplored. Using 10 years of data (2011-2021) from 2,439 adults ages 65 and older in the National Health and Aging Trends Study (NHATS), we examined whether 5-year changes in PEF (2011-2016) were associated with risk for incident dementia over the subsequent 5-year period (2017-2021). PEF slopes for each participant were estimated using linear mixed-effects models and then grouped into quartiles: rapid, moderate, mild, and no declines. Discrete-time Cox proportional hazards models were used to estimate the risk for incident dementia by PEF slope category, while controlling for several health and sociodemographic characteristics. After excluding dementia cases during the exposure window (2011-2016), we identified 338 cases of incident dementia (13.9%) between 2017-2021. Rapid PEF declines between 2011-2016 were associated with 85% higher risk for incident dementia between 2017-2021 compared to those with no declines in PEF (HR=1.85; 95% CI [1.24, 2.76]). Results were robust to several sensitivity analyses. These findings demonstrate that declines in PEF may precede declines in cognition, suggesting that respiratory function may be an important dementia risk factor in older adults. Additionally, these findings highlight the utility of measuring PEF via a peak flow meter, which is a simple and inexpensive measure of respiratory function.

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.

Association between cervical lymph node dissection and dementia: a retrospective analysis

BackgroundDementia, characterized by memory loss and cognitive impairment, considerably impacts individuals and society. Our research focused on cervical lymph nodes, crucial for CNS lymphatic drainage, in the context of dementia. We hypothesized that the patients with head and neck cancer (HNC) undergoing cervical lymph node dissection (CLND) may have increased dementia risk due to obstructed lymphatic pathways. MethodsWe conducted a retrospective analysis of the electronic medical records from patients over 60 years diagnosed with HNC who underwent CLND between March 2007 and April 2023. We collected demographic data, calculated dementia incidence rates, and compared parameters between patients with and without dementia. ResultsAmong the 251 patients with HNC who underwent CLND, 234 were men and 17 were women. Nine male patients developed dementia within an average of 50.1 ± 35.3 months post-surgery. The dementia incidence rate was 0.7 per 100 patient-years, with a cumulative incidence of 10.34% over 8.6 years. The CLND patterns were associated with dementia (p = 0.028), with bilateral supraomohyoid neck dissection (SOHND)/modified radical neck dissection (MRND) and unilateral MRND combined with any neck dissection type on the other side presenting higher risks than unilateral MRND/SOHND (p = 0.016). ConclusionPatients with HNC undergoing bilateral and comprehensive lymph node dissection showed higher dementia risk, highlighting the importance of the neck’s lymphatic role in brain health. These findings may guide future surgical practices.

Target trial emulation using cohort studies: estimating the effect of antihypertensive medication initiation on incident dementia.

Observational studies link high midlife systolic blood pressure to increased dementia risk. However, synthesis of evidence from randomized controlled trials has not definitively demonstrated that antihypertensive medication use reduces dementia risk. Here, we emulate target trials of antihypertensive medication initiation on incident dementia using three cohort studies, with attention to potential violations of necessary assumptions. We emulated trials of antihypertensive medication initiation on incident dementia using data from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Health and Retirement Study (HRS). We used data-driven methods to restrict participants to initiators and non-initiators with overlap in propensity scores and positive control outcomes to look for violations of positivity and exchangeability assumptions. Analyses were limited by the small number of cohort participants who met eligibility criteria. Associations between antihypertensive medication initiation and incident dementia were inconsistent and imprecise (ARIC: HR = 0.30 [0.05, 1.93]; CHS: HR = 0.66 [0.27, 1.64]; HRS: HR = 1.09 [0.75, 1.59]). More stringent propensity score restriction had little effect on findings. Sensitivity analyses using a positive control outcome unexpectedly suggested antihypertensive medication initiation increased risk of coronary heart disease in all three samples. Positive control outcome analyses suggested substantial residual confounding in effect estimates from our target trials, precluding conclusions about the impact of antihypertensive medication initiation on dementia risk through target trial emulation. Formalized processes for identifying violations of necessary assumptions will strengthen confidence in target trial emulation and avoid inappropriate confidence in emulated trial results.

Association of Loneliness with Functional and Cognitive Status in Minor and Major Neurocognitive Disorders.

Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). We diagnosed mild NCD (n = 42) and major NCD (n = 164) through DSM-5 criteria on 206 participants aged > 65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (β = -1.05, p < 0.0001) and minor NCD (β = -0.06, p < 0.01). In the fully adjusted multivariate regression model (sex-age-education-multimorbidity-depressive symptoms-antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (β = 0.09, p < 0.001). The effect of loneliness on IADL (β = -0.26, p < 0.0001) and ADL (β = -0.24, p < 0.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL: β = 0.26, p < 0.0001; ADL: β = 0.05, p = 0.01). Minor NCD displayed different levels of MMSE (β = 6.68, p < 0.001) but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

Interactions between muscle volume and body mass index on brain structure in the UK Biobank.

Low skeletal muscle volume may increase dementia risk through mechanisms affecting brain structure. However, it is unclear whether this relationship exists outside of sarcopenia and/or varies by other factors. We aimed to study the interplay between skeletal muscle volume and factors, such as age, sex, and body mass index (BMI), in explaining brain structure at midlife in a cohort without sarcopenia. We used abdominal and brain magnetic resonance imaging (MRI) data from a population-based cohort enrolled in the UK Biobank. The following measures were derived: thigh fat-free muscle volume (FFMV), total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), total hippocampal volume (THV), and white matter hyperintensity volume (WMHV). Participants below sex-based grip strength thresholds suggesting probable sarcopenia were excluded. Linear regression analysis was used to study the interaction or mediation effects of age, sex, and BMI on the associations between FFMV and brain volumes. Data were available for 20,353 participants (median age 64 years, 53% female). We found interactions between thigh FFMV, BMI, and age (all p < 0.05). Greater thigh FFMV was associated with better brain volumes in those aged <64 years with normal (TBV: β = 2.0 ml/L, p = 0.004; GMV: β = 0.8 ml/L, p = 0.04; WMV: β = 1.1 ml/L, p = 0.006; WMHV: β = -0.2 ml/L, p = 3.7 × 10-5) or low BMI (TBV: β = 21.2 ml/L, p = 0.003; WMV: β = 13.3 ml/L, p = 0.002, WMHV: β = -1.1 ml/L, p = 0.04). Greater thigh muscle volume correlates with better brain volumes at midlife in people without sarcopenia, but this relationship weakens with greater age and BMI. Further study is required to investigate the underlying mechanisms to understand which components of body composition are potentially modifiable risk factors for dementia.

Hypoxemia during rapid eye movement sleep mediates memory impairment in older adults at risk for dementia via CA1 hippocampal volume loss

AbstractBackground and PurposeObstructive sleep apnea is associated with increased dementia risk. Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia.MethodsOlder adults aged ≥50 years (N = 338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (n = 135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index‐3% (REM‐ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high‐resolution hippocampus T2 scans. We determined whether the relationship between REM‐ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non‐REM sleep to determine whether the effects were REM‐specific.ResultsAlthough there was not a direct effect of REM‐ODI on verbal learning (p &gt; 0.05) or memory (p &gt; 0.05), mediation analyses showed a significant indirect effect of high REM‐ODI on poorer verbal learning (β = −0.09, 95% confidence interval [CI] = −0.238 to −0.005) and memory (β = −0.100, 95% CI = −0.255 to −0.005), which was mediated by CA1 volume. These associations were absent in non‐REM sleep (p &gt; 0.05).ConclusionsHypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline.

Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study

BackgroundPrevious research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults.MethodsUsing 2005–2021 data from the National Alzheimer’s Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model.ResultsOf 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7).ConclusionsOur studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.

Association between alcohol consumption and incidence of dementia in current drinkers: linear and non-linear mendelian randomization analysis

Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers. This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe. 313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] units/week and women 9.5 [5.3-16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The non-linear MR failed to identify a significant non-linear causal relationship (p=0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) and summary-level (1.89 [1.53-2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk. This study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia. The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.

Attitudes Towards Dementia Among a Diverse Group of Refugees Resettled in the United States.

Forced migration results in exposure to trauma, interrupted access to healthcare, and loss of social support and may increase dementia risk. Literature on refugees' knowledge of dementia and its risk factors is scant. This study investigates refugee perspectives on dementia and their access to cognitive healthcare in the United States (US). We conducted 6 focus groups and 30 individual in-depth interviews (total of 69 participants) with Arab, African, and Afghan refugees resettled in San Diego, California. Data was coded using inductive thematic analysis. Organized by the socioecological model of health, the following themes emerged: (1) mental trauma due to migration was linked to dementia (individual); (2) fear of dementia and burdening caregivers due to limited support systems (interpersonal); (3) reliance on virtual communities for dementia information and the stress of local community loss increasing dementia risk (community); (4) healthcare providers, both in the US and in refugee camps, didn't address cognitive health concerns (institutions); and (5) discriminatory immigration and healthcare policies as barriers to healthy aging (policy). Despite being a heterogeneous group, refugees share specific experiences, knowledge gaps, and barriers to healthy aging. Tailored interventions and policies are needed to address this population's cognitive health needs. This includes addressing their mental health and social support concerns as well as training clinicians to screen for/discuss dementia with aging refugee patients.

Association of sleep duration with excess risk of dementia among shift workers in the UK biobank: a population-based cohort study.

Shift work was associated with elevated dementia risk. Definitive guidelines for sleep duration among shift workers have not been proposed. We aimed to identify sleep durations associated with elimination of excess dementia risk in shift workers. 285,213 dementia-free UK Biobank participants at baseline, aged 38-71years, were enrolled between 2006 and 2010 and followed up through 2022 in this cohort study. Cox proportional hazards models were used to examine the associations between shift work, sleep duration, and risk of dementia. The 285,213 participants included 49,079 shift workers and 236,134 non-shift workers. Over a median follow-up of 13.8years, 1887 dementia cases were documented. Current shift workers had significantly higher dementia risk than non-shift workers (hazard ratio [HR] 1.26; 95% CI 1.11-1.42). However, this excess risk was eliminated in shift workers with 8h of sleep (HR 1.02; 95% CI 0.80-1.29). Analysis of shift work frequency indicated that "sometimes" and "usually/always" shift work were associated with increased dementia risk compared to that of non-shift workers, but excess dementia risk was eliminated in members of either frequency group receiving 8h of sleep ("sometimes", HR 1.05; 95% CI 0.75-1.48; "usually/always", HR 0.98; 95% CI 0.70-1.35). Both "non-night shift" and "night shift" workers showed increased dementia risk compared to non-shift workers. Workers with 8h of sleep mitigated the excess risk (HR 1.13; 95% CI 0.84-1.53 and HR 0.86; 95% CI 0.59-1.26, respectively). 8-h sleep may eliminate excess dementia risk among shift workers, suggesting a potentially effective dementia prevention guideline for shift workers.

Relationships of hematocrit concentration with dementia from a multiethnic population-based study.

Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

Protective role of serum albumin in dementia: a prospective study from United Kingdom biobank.

A number of studies have explored the link between neurodegenerative disorders (NDDs) and albumin, the main protein in human plasma. However, the results have been inconsistent, highlighting the necessity for a detailed systemic analysis. Utilizing data from the United Kingdom Biobank, we investigated the relationship between baseline levels of serum and urine albumin and the occurrence of common NDDs, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and dementia, employing Cox proportional hazards regression analysis. Our results reveal that elevated baseline serum albumin levels are linked to a decreased risk of developing dementia (beta = -0.024, SE = 0.004, p < 0.001). Subgroup and interaction analyses highlighted the impact of factors like body mass index (BMI), age, and alcohol consumption on this relationship. Specifically, participants with higher BMI, younger age, or lower alcohol intake exhibited a stronger protective effect. On the other hand, a higher baseline level of urine microalbumin was connected to a slight increase in dementia risk (beta = 0.003, SE = 3.30E-04, p < 0.001). No significant associations were found between albumin levels and the risk of PD or ALS. Our study underscores the potential role of serum albumin as a biomarker associated with reduced dementia risk. These findings contribute valuable insights into the understanding of albumin's impact on NDDs, suggesting its utility as a biomarker for dementia in clinical settings and informing future therapeutic strategies in clinical trials.

Association of birthweight and risk of incident dementia: a prospective cohort study.

Given the epidemiological studies investigating the relationship between birthweight and dementia are limited. Our study aimed to explore the association between birthweight and the risk of dementia, cognitive function, and brain structure. We included 275,648 participants from the UK Biobank, categorizing birthweight into quartiles (Q1 ≤ 2.95 kg; Q2 > 2.95 kg, ≤ 3.32 kg; Q3 > 3.32 kg, ≤ 3.66 kg; Q4 > 3.66 kg), with Q3 as the reference. Cox regression models and restricted cubic splines estimated the relationship between birthweight and the risk of all causes of dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Multivariable linear regression models assessed the relationship between birthweight, cognitive function, and MRI biomarkers. Over a median follow-up of 13.0 years, 3103 incident dementia cases were recorded. In the fully adjusted model, compared to Q3 (> 3.32 kg, ≤ 3.66 kg), lower birthweight in Q1 (≤ 2.95 kg) was significantly associated with increased risk of ACD (HR = 1.18, 95%CI 1.06-1.30, P = 0.001) and VD (HR = 1.32, 95%CI 1.07-1.62, P = 0.010), but no significant association with AD was found. Continuous birthweight showed a U-shaped nonlinear association with dementia. Lower birthweight was associated with worse performance in cognitive tasks, including reaction time, fluid intelligence, numeric, and prospective memory. Additionally, certain brain structure indices were identified, including brain atrophy and reductions in area, thickness, and volume of regional subcortical areas. Our study emphasizes the association between lower birthweight and increased dementia risk, correlating cognitive function and MRI biomarkers of brain structure, suggesting that in utero or early-life exposures might impact cognitive health in adulthood.

Associations of Post-Traumatic Stress Disorder and Objective Subtle Cognitive Difficulties in Cognitively Unimpaired Older Veterans.

Psychiatric conditions such as post-traumatic stress disorder (PTSD) and depression have a two-fold increased dementia risk in Veterans. Prior work has shown that psychiatric factors can both impact cognitive functioning and be early symptoms associated with Alzheimer's disease (AD). Objectively defined subtle cognitive difficulties (Obj-SCD) has been associated with cognitive decline and AD biomarkers. However, Obj-SCD has not yet been investigated in the context of psychiatric disorders. A total of 179 cognitively unimpaired Veterans (50-92years old) underwent a comprehensive neuropsychological evaluation at VA San Diego and a retrospective medical record review. Chi-squared tests compared rates of psychiatric diagnoses in Veterans with and without Obj-SCD. About 21% of the sample was classified as Obj-SCD. Relative to cognitively unimpaired Veterans, Veterans classified as Obj-SCD had higher rates of PTSD, but not higher rates of other psychiatric conditions (e.g., depression). The PTSD findings appear to be driven by measures of cognitive efficiency. Elevated rates of PTSD, but not other psychiatric conditions, were observed among Veterans with Obj-SCD. The prevalence and type of subtle cognitive difficulties associated with PTSD in older Veterans demonstrates a need, and informs potential targets, for intervention. Further work is needed to determine mechanisms of subtle cognitive difficulties in older Veterans with PTSD.

Social cohesion as a modifier of joint air pollution exposure and incident dementia

Social cohesion can reduce stress, increase social interaction, and improve cognitive reserve. These social mechanisms may modify the effects of air pollution on dementia risk. This cohort study examines the potential moderating effect of social cohesion on associations between joint air pollution exposure and incident dementia leveraging data from 5112 community-dwelling adults ≥65 years of age enrolled in the National Health and Aging Trends Study (NHATS). Study participants were enrolled in 2011 and followed through 2018. We assigned 2010 residential census tract-level exposures to five air pollutants, particulate matter (PM) ≤ 10 μm in diameter, PM ≤ 2.5 μm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide, using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Dementia status was determined based on self- or proxy-reported dementia diagnosis or “probable dementia” according to NHATS cognitive screening tools. Participants' self-rated neighborhood social cohesion was evaluated based on three questions: neighbors knowing each other, being helpful, and being trustworthy. Social cohesion was dichotomized at the median into high vs low social cohesion. Associations between air pollutants and incident dementia were assessed using quantile g-computation Cox proportional hazard models and stratified by high vs low social cohesion, adjusting for age, sex, education, partner status, urbanicity, annual income, race and ethnicity, years lived at current residence, neighborhood disadvantage index, and tract segregation. High social cohesion (HR = 1.20, 95 % CI = 0.98, 1.47) and air pollution (HR = 1.08, 95 % CI = 0.92, 1.28) were not associated with incident dementia alone. However, when stratified, greater joint air pollution exposure increased dementia risk among participants at low (HR = 1.34, 95 % CI = 1.04, 1.72), but not high (HR = 1.00, 95 % CI = 0.93, 1.06) social cohesion. Air pollution was a risk factor for dementia only when reported social cohesion was low, suggesting that social interaction may play a protective role, mitigating dementia risk via air pollution exposure.

Role of uric acid in neurodegenerative diseases, focusing on Alzheimer and Parkinson disease: A new perspective.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini-review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress-induced neurodegeneration in AD and PD. However, long-term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.