Elevated Risk Of Dementia Research Articles

Schizophrenia, Off-Label Antipsychotics, and Dementia Risk in People with HIV.

Comorbidities such as schizophrenia and medication such as antipsychotics may influence the risk of dementia among people living with HIV (PLWH). The objective of this paper is to assess the associations among HIV patients with schizophrenia, off-label antipsychotics, and dementia risk. US Department of Veterans Affairs healthcare facilities from 2000 to September 2023. Retrospective cohort study of PLWH treated by the U.S. Department of Veterans Affairs with prior history of schizophrenia, off-label antipsychotic use and neither schizophrenia nor antipsychotic use. Propensity score matched non-HIV controls were included for the respective HIV groups. The hazard of dementia is estimated using Cox proportional hazards models. PLWH and schizophrenia, were found to have a 2.49 higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=2.49, 95%CI=(1.85-3.35)). PLWH and off-label antipsychotic use were found to have a 1.77-fold higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=1.77, 95% CI=(1.37-2.28)). Propensity score matched analysis reveals that, among schizophrenia patientis, those with HIV had a 1.65-fold higher hazard of dementia (HR=1.65, 95%CI=(1.12-2.44)). Among patients with no schizophrenia or antipsychotic medication, those with HIV had a 1.47 fold higher hazard of dementia (HR=1.47, 95%CI=(1.33-1.63)). This study demonstrates that among PLWH, history of schizophrenia or off-label antipsychotic medication use are associated with substantial increases in dementia incidence. Furthermore, propensity-matched control analysis reveals that HIV infection itself is independently and significantly associated with elevated dementia risk.

Relationship between hearing impairment and dementia and cognitive function: a Mendelian randomization study

BackgroundThere is a substantial body of observational research indicating an association between hearing impairment and dementia, yet the causal relationship and underlying mechanisms remain uncertain. This study aims to investigate the causal relationship between hearing impairment and its subtypes with dementia and cognitive function using two-sample Mendelian randomization (MR) analysis.MethodsWe performed two-sample MR analysis to examine the causal effects of hearing impairment and its subtypes, including conductive and sensorineural hearing loss (CSHL), conductive hearing loss (CHL), sensorineural hearing loss (SHL), and sudden sensorineural hearing loss (SIHL), on six dementia phenotypes (overall dementia, Alzheimer’s disease [AD], Lewy body dementia [DLB], frontotemporal dementia [FTD], Parkinson’s disease dementia, and vascular dementia) and four cognitive functions. Additionally, multivariable MR (MVMR) analysis was employed to investigate potential mediating mechanisms.ResultsGenetically determined CSHL was associated with an elevated risk of DLB (odds ratio [OR] 1.69; 95% CI 1.08 to 2.63; P = 0.021) and FTD (OR 1.66; 1.04 to 2.67; P = 0.035), but not AD (P = 0.958). Genetic predisposition to CHL was found to link with increased risks of AD (OR 1.07; 1.01 to 1.14; P = 0.031). Genetically determined SHL was causally associated with an elevated risk of semantic dementia (OR 3.81; 1.09 to 13.37; P = 0.037). Genetically predicted CHL and SIHL were both causally associated with lower general cognitive performance (β -0.015 and − 0.043; P = 0.007 and 0.013) and fluid intelligence score (β -0.045 and − 0.095; P = 0.037 and 0.040). In MVMR analysis, the causal relationship between hearing impairment and dementia was mediated by loneliness, depressed mood, and brain cortical volume, particularly the medial temporal lobe, but not by aging or ischemic stroke.ConclusionOverall, the study provides evidence supporting a causal relationship between hearing impairment and increased risks of different types of dementia (including AD, FTD, and DLB), as well as poorer general cognitive function. These findings underscore the importance of addressing hearing impairment as a modifiable risk factor for dementia.

Associations of metabolic syndrome with cognitive function and dementia risk: Evidence from the UK Biobank cohort.

To investigate the associations of metabolic syndrome (MetS) with cognitive function, dementia and its subtypes. Based on the participants recruited by UK Biobank, this study aims to investigate the associations of MetS with cognitive function, dementia and its subtypes. Generalized estimating equations, Cox proportional risk models, and multiple linear regression models were respectively used to assess associations between MetS and dementia-related outcomes. Among the 363,231 participants, 95,713 had MetS at baseline. The results showed that MetS was significantly associated with cognitive function related to fluid intelligence and prospective memory at follow-up. Among participants aged ≥60 years, MetS was correlated with elevated risk of all-cause dementia, particularly vascular dementia (VaD) [hazard ratio 1.115 (95% confidence interval: 1.047, 1.187), hazard ratio 1.393 (95% confidence interval: 1.233, 1.575), respectively]. With increasing MetS components, the risk of all-cause dementia and VaD tended to be elevated. MetS has also been associated with dementia-related structural changes in the brain, including alterations in overall brain volume, white matter volume, grey matter volume and white matter integrity. MetS was associated with poorer cognitive performance and might increase the risk of all-cause dementia as well as VaD, but the effect on Alzheimer's disease was not significant. Holistic control of the MetS may benefit the prevention and control of cognitive impairment and dementia.

Psychosocial Health and the Association Between Cerebral Small Vessel Disease Markers With Dementia: The ARIC Study.

Associations between magnetic resonance imaging markers of cerebral small vessel disease (CSVD) and dementia risk in older adults have been established, but it remains unclear how lifestyle factors, including psychosocial health, may modify this association. Social support and social isolation were assessed among participants of the community-based ARIC (Atherosclerosis Risk in Communities) Study, via self-reported questionnaires (1990-1992). Following categorization of both factors, participants were classified as having strong or poor mid-life social relationships. At visit 5 (2011-2013), participants underwent 3T brain magnetic resonance imaging quantifying CSVD measures: white matter hyperintensity volume, microbleeds (subcortical), infarcts (lacunar), and white matter integrity (diffusion tensor imaging). Incident dementia cases were identified from the time of imaging through December 31, 2020 with ongoing surveillance. Associations between CSVD magnetic resonance imaging markers and incident dementia were evaluated using Cox proportional-hazard regressions adjusted for demographic and additional risk factors (from visit 2). Effect modification by mid-life social relationships was evaluated. Of the 1977 participants with magnetic resonance imaging, 1617 participants (60.7% women; 26.5% Black participants; mean age at visit 2, 55.4 years) were examined. In this sample, mid-life social relationships significantly modified the association between white matter hyperintensity volume and dementia risk (P interaction=0.001). Greater white matter hyperintensity volume was significantly associated with risk of dementia in all participants, yet, more substantially in those with poor (hazard ratio, 1.84 [95% CI, 1.49-2.27]) versus strong (hazard ratio, 1.26 [95% CI, 1.08-1.47]) mid-life social relationships. Although not statistically significant, subcortical microbleeds in participants with poor mid-life social relationships were associated with a greater risk of dementia, relative to those with strong social relationships, in whom subcortical microbleeds were no longer associated with elevated dementia risk. The elevated risk of dementia associated with CSVD may be reduced in participants with strong mid-life social relationships. Future studies evaluating psychosocial health through the life course and the mechanisms by which they modify the relationship between CSVD and dementia are needed.

A randomized, placebo-controlled trial of purified anthocyanins on cognitive function in individuals at elevated risk for dementia: Analysis of inflammatory biomarkers toward personalized interventions

BackgroundDementia poses a significant global health challenge. Anthocyanins neutralize free radicals, modulate signaling pathways, inhibit pro-inflammatory genes, and suppress cytokine production and may thus have positive cognitive effects in people at increased risk of dementia. We aim to investigate the effects of purified anthocyanins on cognitive function in people at increased risk of dementia according to their inflammation status based on blood-based inflammatory biomarkers. MethodsThis is a secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial. Cluster analysis was performed to categorize two groups based on their individual inflammatory biomarker profile using multiplex sandwich ELISA for the quantitative measurement of cytokines. Descriptive statistics and longitudinal models assessed cognitive outcomes. The primary comparison was the group difference at week 24 based on a modified intention-to-treat analysis. ResultsCluster analysis revealed two distinct inflammatory biomarker profiles. In Cluster 1 (high levels of inflammation biomarkers), anthocyanin treatment showed a statistically significant improvement on cognitive function compared to placebo at 24 weeks. No significant differences were observed in Cluster 2 (low levels of inflammation biomarkers). The demographic characteristics, cognitive scores, and biomarker distributions were similar between treatment groups at baseline. However, cluster 1 exhibited higher BMI, diabetes prevalence, medication usage, and lower HDL cholesterol levels. ConclusionIndividuals with elevated levels of inflammation markers benefited from anthocyanin treatment to enhance cognitive performance, whereas those with lower levels did not. The anti-inflammatory and antioxidant properties of anthocyanins make them a promising intervention, and future prospective trials in people with increased inflammation are warranted.

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.

Post-diagnosis smoking habit change and incident dementia in cancer survivors.

Many individuals change their smoking habits after cancer diagnosis. We aimed to evaluate the association of post-diagnosis smoking habit change with incident dementia in cancer survivors. We identified 558,127 individuals who were diagnosed with cancer at age ≥ 20 and survived for ≥ 3 years. Participants were classified into four groups: (1) sustained non-smokers, (2) initiators/relapsers, (3) quitters, and (4) continuing smokers. Dementia risk in each group was assessed using a cause-specific Cox model. After cancer diagnosis, 2.3% of pre-diagnosis non-smokers initiated/relapsed into smoking, while 51.7% of pre-diagnosis smokers quit smoking. Compared to sustained non-smokers, multivariable-adjusted risk of dementia was 29% higher among initiators/relapsers, 11% higher among quitters, and 31% higher among continuing smokers. Compared to continuing smokers, the risk was 15% lower among quitters. In cancer survivors, smoking initiation/relapse was associated with increased risk of dementia, whereas smoking cessation was associated with decreased risk of dementia. Approximately half of pre-diagnosis smokers quit smoking after a cancer diagnosis. Smoking cessation was associated with a 15% reduced risk of dementia. More than 2% of pre-diagnosis non-smokers initiated or relapsed into smoking after a cancer diagnosis. Smoking initiation/relapse was associated with a 29% elevated risk of dementia.

Time to Dementia Diagnosis Among Veterans with Comorbid Insomnia and Depressive Episodes.

Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratio = 1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratio = 1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms.

Interaction between alimentary surgery and risk of dementia: a nationwide population-based case-control study.

Based on current research, it is known that the gastrointestinal tract microbiota and its genome play a crucial role in mental illnesses. Studies indicate a direct correlation between gastrointestinal tract microbiota and the onset of dementia, mediated by metabolic diseases and low-grade inflammation. The association between various gastrointestinal symptoms and neurodegenerative diseases has been recently discussed. However, there is a lack of research regarding the comparative effects of different surgical procedures on neurodegenerative diseases. Therefore, this study primarily focuses on comparing the association between various gastrointestinal surgeries and dementia, aiming to provide guidance for future clinical practice. A nationwide study using the Taiwanese National Health Insurance Research Database included 26 059 patients diagnosed with dementia or Alzheimer's disease and 104 236 controls without diseases. Primary exposures were defined as alimentary surgeries, encompassing cholecystectomy, gastrectomy, bowel resection, and appendectomy. Conditional logistic regression was used to examine the odds ratio and 95% confidence interval for prior alimentary surgery between cases and controls. The results showed that individuals with dementia had a higher rate of gastrectomy. Additionally, individuals with dementia seemed to exhibit a reduced rate of cholecystectomy and appendectomy. Regarding Alzheimer's disease, all four alimentary surgeries showed comparable trends to those observed with dementia. No significant interaction was observed between alimentary surgery and dementia among the four types of surgery evaluated. Our study demonstrates that gastrectomy is associated with an elevated risk of dementia. We aim to uncover more direct evidence in future experiments.

Association of Alzheimer's disease polygenic risk score with concussion severity and recovery metrics.

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six outcomes in 931 total participants. The outcomes were two concussion recovery measures (number of days to asymptomatic status, number of days to return to play (RTP)) and four concussion severity measures (scores on SAC and BESS, SCAT symptom severity, and total number of symptoms). We calculated PRS using a published score [1] and performed multiple linear regression (MLR) to assess the relationship of PRS with the outcomes. We also used t-tests and chi-square tests to examine outcomes by APOE genotype, and MLR to analyze outcomes in European and African genetic ancestry subgroups. Higher PRS was associated with longer injury to RTP in the normal RTP (<24 days) subgroup ( p = 0.024), and one standard deviation increase in PRS resulted in a 9.89 hour increase to the RTP interval. There were no other consistently significant effects, suggesting that high AD genetic risk is not strongly associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

Associations of ambient air pollution exposure and lifestyle factors with incident dementia in the elderly: A prospective study in the UK Biobank

ObjectiveDementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. MethodsThis study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. ResultsDuring a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standarddeviationincrease in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer’s disease (AD), but no significant modification effects are found for sleep patterns or smoking status. ConclusionThe increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.

Validation of Different Dementia Code-Based Definitions in a Population-Based Study of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. This study aimed to examine how different diagnostic dementia definitions perform in patients with RA compared to individuals without RA. The study population included 2050 individuals (1025 with RA) from a retrospective, population-based cohort in southern Minnesota and compared the performance of 3 code-based dementia diagnostic algorithms with medical record review diagnosis of dementia. For the overall comparison, each patient's complete medical history was used, with no time frames. Sensitivity analyses were performed using 1-, 2-, and 5-year windows around the date that dementia was identified in the medical record (reference standard). Algorithms performed very similarly in persons with and without RA. The algorithms generally had high specificity, negative predictive values, and accuracy, regardless of the time window studied (> 88%). Sensitivity and positive predictive values varied depending on the algorithm and the time window. Sensitivity values ranged 56.5-95.9%, and positive predictive values ranged 55.2-83.1%. Performance measures declined with more restrictive time windows. Routinely collected electronic health record (EHR) data were used to define code-based dementia diagnostic algorithms with good performance (vs diagnosis by medical record review). These results can inform future studies that use retrospective databases, especially in the same or a similar EHR infrastructure, to identify dementia in individuals with RA.

Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis

H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. To explore dementia risk in patients with allergic rhinitis using AHs. Taiwanese patients with new-onsetallergic rhinitis (2011-2017) constituted the study population (677,971 with FGAs or SGAs, 36,081 without AHs). AH use was measured in cumulative defined daily dose (cDDD). Patients were grouped by cDDD (nonuser, <60 cDDD, 60-120 cDDD, and >120 cDDD). A Cox proportional hazard model assessed the AH-dementia association. Sensitivity analysis explored AH effects on dementia risk across subgroups and associations between specific AHs and dementia types. FGAs in patients with allergic rhinitis were associated with elevated dementia risk. At less than 60 cDDD, adjusted hazard ratio (aHR) was 1.13 (95% CI, 1.09-1.17); at 60 to 120 cDDD, aHR was 1.29 (95% CI, 1.21-1.38); and at more than 120 cDDD, aHR was 1.51 (95% CI, 1.42-1.62). SGAs also raised dementia risk. At less than 60 cDDD, aHR was 1.11 (95% CI, 1.05-1.17); at 60 to 120 cDDD, aHR was 1.19 (95% CI, 1.12-1.26); and at more than 120 cDDD, aHR was 1.26 (95% CI, 1.19-1.33). Patients with allergic rhinitis on FGAs or SGAs face an escalating dementia risk with increasing cumulative dosage. Moreover, FGAs exhibit a higher dementia risk compared with SGAs. Nevertheless, extensive clinical trials are imperative for confirming the association between FGA use, SGA use, and dementia risk.

Mapping the interplay of atrial fibrillation, brain structure, and cognitive dysfunction.

Atrial fibrillation (AF) is associated with an elevated risk of cognitive impairment and dementia. Understanding the cognitive sequelae and brain structural changes associated with AF is vital for addressing ensuing health care needs. We examined 1335 stroke-free individuals with AF and 2683 matched controls using neuropsychological assessments and multimodal neuroimaging. The analysis revealed that individuals with AF exhibited deficits in executive function, processing speed, and reasoning, accompanied by reduced cortical thickness, elevated extracellular free-water content, and widespread white matter abnormalities, indicative of small vessel pathology. Notably, brain structural differences statistically mediated the relationship between AF and cognitive performance. Integrating a comprehensive analysis approach with extensive clinical and magnetic resonance imaging data, our study highlights small vessel pathology as a possible unifying link among AF, cognitive decline, and abnormal brain structure. These insights can inform diagnostic approaches and motivate the ongoing implementation of effective therapeutic strategies. Highlights We investigated neuropsychological and multimodal neuroimaging data of 1335 individuals with atrial fibrillation (AF) and 2683 matched controls. Our analysis revealed AF-associated deficits in cognitive domains of attention, executive function, processing speed, and reasoning. Cognitive deficits in the AF group were accompanied by structural brain alterations including reduced cortical thickness and gray matter volume, alongside increased extracellular free-water content as well as widespread differences of white matter integrity. Structural brain changes statistically mediated the link between AF and cognitive performance, emphasizing the potential of structural imaging markers as a diagnostic tool in AF-related cognitive decline.

Mid- and Late-Life Chronic Kidney Disease Is Associated with Parkinson's Disease, Not with an Increased Risk of Alzheimer's Disease.

Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This study investigated the prospective association of patients with CKD aged ≥55 years with an increased risk of Alzheimer's or Parkinson's disease. We conducted a retrospective cohort analysis using a national cohort sample of approximately one million patients. Primary outcome indicators measured included incidence of all-cause dementia, Alzheimer's disease, and Parkinson's disease events using person-years at risk. The hazard ratio was adjusted using the Cox proportional hazards model. We included 952 patients without CKD and 476 with CKD over 55 years using propensity score matching. The CKD group exhibited higher incidences of all-cause dementia, Parkinson's disease, and Alzheimer's disease than the non-CKD group. Furthermore, the CKD group had an elevated risk of all-cause dementia and a significantly increased risk of Parkinson's disease, especially among older women. Notably, the risk of Parkinson's disease was higher within the first 3 years of CKD diagnosis. These findings emphasize the link between CKD in mid- and late-life individuals and a higher incidence of all-cause dementia and Parkinson's disease rather than Alzheimer's disease.

Osteoporosis as a Potential Modifiable Risk Factor for Dementia in Thailand: A Cross-Sectional Analysis.

This study aims to explore the potential of osteoporosis as a modifiable risk factor for dementia and investigatewhether treatments like estrogen supplementation and bisphosphonates can reduce the risk of dementia in the Thai population. This study aimed to evaluate the risk of dementia in patients with osteoporosis. A cross-sectional analysis was conducted. Participants aged <50 years and those with a history of dementia at baseline were excluded. Clinical variables were analyzed using the chi-squared test. Logistic regression analysis was conducted to determine independent factors of dementia after adjusting for potential confounders. The cohort was conducted on 54,399 participants, of whom 9763 (17.9%) had osteoporosis. The results indicated that individuals with osteoporosis had an odds ratio (OR) of 1.62-fold higher risk of developing dementia compared to those without osteoporosis (95% confidence interval (CI) 1.37-1.92, p-value < 0.001). Furthermore, compared to patients with osteoporosis not undergoing any treatment, those receiving estrogen supplementation and bisphosphonate treatment showed reduced associations with dementia, with an OR of 0.84 (95% CI 0.73-0.98, p-value = 0.023) and 0.66 (95% CI 0.60-0.73, p-value < 0.001), respectively. The study findings suggest an elevated risk of dementia in patients with osteoporosis and contribute substantially to our understanding of the link between osteoporosis and dementia in the Thai population.

The Elevated Risk of Dementia in Parkinson's Disease Patients Associated with Metabolic Syndrome

The Elevated Risk of Dementia in Parkinson's Disease Patients Associated with Metabolic Syndrome

Diabetes-related clinical and microstructural white matter changes in patients with Alzheimer's disease.

Although there exists substantial epidemiological evidence indicating an elevated risk of dementia in individuals with diabetes, our understanding of the neuropathological underpinnings of the association between Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) remains unclear. This study aims to unveil the microstructural brain changes associated with T2DM in AD and identify the clinical variables contributing to these changes. In this retrospective study involving 64 patients with AD, 31 individuals had concurrent T2DM. The study involved a comparative analysis of diffusion tensor imaging (DTI) images and clinical features between patients with and without T2DM. The FSL FMRIB software library was used for comprehensive preprocessing and tractography analysis of DTI data. After eddy current correction, the "bedpost" model was utilized to model diffusion parameters. Linear regression analysis with a stepwise method was used to predict the clinical variables that could lead to microstructural white matter changes. We observed a significant impairment in the left superior longitudinal fasciculus (SLF) among patients with AD who also had T2DM. This impairment in patients with AD and T2DM was associated with an elevation in creatine levels. The white matter microstructure in the left SLF appears to be sensitive to the impairment of kidney function associated with T2DM in patients with AD. The emergence of AD in association with T2DM may be driven by mechanisms distinct from the typical AD pathology. Compromised renal function in AD could potentially contribute to impaired white matter integrity.

Sarcopenic obesity is part of obesity paradox in dementia development: evidence from a population-based cohort study

BackgroundSarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset.MethodsWe included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined.ResultsObese women with high PRS had a decreased risk (HR = 0.855 [0.761–0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045–1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HRwomen = 1.323 [1.064–1.644]; HRmen = 2.144 [1.753–2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HRwomen = 1.679 [1.355–2.081]; HRmen = 2.069 [1.656–2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HRwomen = 1.424 [1.227–1.653]; HRmen = 1.989 [1.702–2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases.ConclusionsSarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.

Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study

BackgroundThe global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk.MethodsOur prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors.ResultsOver a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19–1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51–2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 μmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02–1.21; VD: HR = 1.50, 95% CI = 1.28–1.77).ConclusionsOur study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.