Dementia Status Research Articles

Community paramedicine in dementia care.

Novel hospital diversion strategies are needed to support a growing number of patients with dementia living in the community. One promising model is community paramedicine (CP), which deploys paramedics to the home, who consult with a physician to coordinate treatment and assess disposition. While evidence suggests CP can manage many patients without escalation to the emergency department (ED), no studies have evaluated optimal CP utilization for patients with dementia. Therefore, we compare the use and outcomes of CP for homebound patients with and without dementia. This retrospective cohort study examines 251 homebound patients receiving home-based primary care, who utilized a physician-led CP service between March 2017 and May 2022. Linked electronic health record data included patient demographics, clinical characteristics, and CP encounter details. Dementia status and CP outcomes, including rates of ED transport, over-transport (i.e., transported, but not hospitalized), and under-transport (i.e., not transported, but ED visit within 3 days), were determined via chart review. Using logistic regression, we modeled the association of dementia status with over- and under-transport, adjusting for age, sex, and chief complaint. Fifty-three percent of CP patients had dementia. Their most common chief complaints were dyspnea (24.3%), altered mental status (17.9%), and generalized weakness (9.8%). We found no significant difference in ED transport rates by dementia status (25.4 vs. 22.8%, p = 0.54). Dementia diagnosis was associated with lower rates of over-transport (OR = 0.21, p = 0.03, CI [0.05, 0.85]) and comparable rates of under-transport (OR = 0.70, p = 0.47, CI [0.27, 1.83]) in adjusted models. CP has effectively managed a diverse population of homebound patients with dementia cared for via home-based primary care. Future work should examine potential cost savings and use of CP in dementia care across geographic and healthcare settings.

Impact of dementia status on intravenous thrombolysis and endovascular treatment for acute ischemic stroke: Retrospective study

IntroductionIndividuals with dementia are underrepresented in interventional studies for acute ischemic stroke (AIS). This research gap creates a bias against their treatment in clinical practice. Our goal was to compare the safety and efficacy of intravenous-thrombolysis (t-PA) and endovascular treatment (EVT) in individuals with or without pre-AIS dementia. MethodA retrospective study of AIS patients receiving t-PA or EVT between 2019 and 2022. Patients were classified as dementia on a case-by-case review of baseline assessment. Additional variables included demographic, vascular risk factors, AIS severity and treatment. Outcomes of interest were intracerebral hemorrhage, mortality in 90-days, and the difference in modified rankin scale (mRS) before AIS and in 90-days follow-up. Outcomes were compared across non-matched groups and following propensity-score matching. ResultsAltogether, 628 patients were included, of which 68 had pre-AIS dementia. Compared to non-dementia group, dementia group were older, had a higher rate of vascular risk factors, higher pre-stroke mRS and higher baseline NIHSS. Individuals with dementia had higher rates of mortality (25% vs.11%,p < 0.01) on non-matched comparison. All cohort and restricted t-PA EVT matched analysis showed no difference in any outcome. Regression analysis confirmed that AIS severity at presentation and its treatment, not dementia, were the chief contributors to patients' outcomes. DiscussionOur results indicate that pre-AIS dementia does not impact the efficacy or safety of EVT or t-PA for AIS. We thus call for more inclusive research on stroke therapy with regards to baseline cognitive status. Such studies are urgently required to inform stroke guidelines and enhance care.

Association of level of adherence to Mediterranean diet with cognitive and dementia status in subjects with chronic diseases: a cross-sectional study

ABSTRACT Background The Mediterranean diet has been linked to brain neuroprotection. Evidence from meta-analyses showed reduced risk of dementia with greater intake of vegetables and fruits, fish, and the Mediterranean diet. The current study raises important questions about the association between low risk dementia and Mediterranean diet. Objective The objective was to evaluate the association between levels of adherence to the Mediterranean diet and dementia and cognitive status in subjects 50 years of age and older. Method The Mediterranean Diet Adherence Screener (MEDAS), the modified 30-item ‘Diagnostic and Statistical Manual of Mental Disorders Third Edition (DSM-III) risk of dementia, and the Standard Mini-Mental Status Examination (SMMSE) cognitive status scores were used to assess the levels of adherence to the Mediterranean diet’. Results A total of 150 subjects were enrolled in the study. Forty-one (27.3%) had ‘suspected or confirmed dementia, while 48 individuals (32%) were categorized as having moderate to severe cognitive decline. Subjects who reported moderate to high adherence to the Mediterranean diet (55, 36.7%) had significantly lower dementia scores (7.0 3.8 versus 17.6 5.1) and higher cognitive (25.4 3.8 versus 8.6 7.2) scores compared to those (38, 25.3%) who reported low adherence to the Mediterranean diet. Conclusion Subjects who were highly or moderately adherent to the Mediterranean diet had significantly lower dementia scores and better cognitive status than those with low adherence.

Dementia risk and thalamic nuclei volumetry in healthy midlife adults: the PREVENT Dementia study.

A reduction in the volume of the thalamus and its nuclei has been reported in Alzheimer's disease, mild cognitive impairment and asymptomatic individuals with risk factors for early-onset Alzheimer's disease. Some studies have reported thalamic atrophy to occur prior to hippocampal atrophy, suggesting thalamic pathology may be an early sign of cognitive decline. We aimed to investigate volumetric differences in thalamic nuclei in middle-aged, cognitively unimpaired people with respect to dementia family history and apolipoprotein ε4 allele carriership and the relationship with cognition. Seven hundred participants aged 40-59 years were recruited into the PREVENT Dementia study. Individuals were stratified according to dementia risk (approximately half with and without parental dementia history). The subnuclei of the thalamus of 645 participants were segmented on T1-weighted 3 T MRI scans using FreeSurfer 7.1.0. Thalamic nuclei were grouped into six regions: (i) anterior, (ii) lateral, (iii) ventral, (iv) intralaminar, (v) medial and (vi) posterior. Cognitive performance was evaluated using the computerized assessment of the information-processing battery. Robust linear regression was used to analyse differences in thalamic nuclei volumes and their association with cognitive performance, with age, sex, total intracranial volume and years of education as covariates and false discovery rate correction for multiple comparisons. We did not find significant volumetric differences in the thalamus or its subregions, which survived false discovery rate correction, with respect to first-degree family history of dementia or apolipoprotein ε4 allele status. Greater age was associated with smaller volumes of thalamic subregions, except for the medial thalamus, but only in those without a dementia family history. A larger volume of the mediodorsal medial nucleus (Pfalse discovery rate = 0.019) was associated with a faster processing speed in those without a dementia family history. Larger volumes of the thalamus (P = 0.016) and posterior thalamus (Pfalse discovery rate = 0.022) were associated with significantly worse performance in the immediate recall test in apolipoprotein ε4 allele carriers. We did not find significant volumetric differences in thalamic subregions in relation to dementia risk but did identify an interaction between dementia family history and age. Larger medial thalamic nuclei may exert a protective effect on cognitive performance in individuals without a dementia family history but have little effect on those with a dementia family history. Larger volumes of posterior thalamic nuclei were associated with worse recall in apolipoprotein ε4 carriers. Our results could represent initial dysregulation in the disease process; further study is needed with functional imaging and longitudinal analysis.

Chronic traumatic encephalopathy and aging-related tau astrogliopathy in community-dwelling older persons with and without moderate-to-severe traumatic brain injury.

This study examined the frequency of chronic traumatic encephalopathy-neuropathologic change (CTE-NC) and aging-related tau astrogliopathy (ARTAG) in community-dwelling older adults and tested the hypothesis that these tau pathologies are associated with a history of moderate-to-severe traumatic brain injury (msTBI), defined as a TBI with loss of consciousness >30 minutes. We evaluated CTE-NC, ARTAG, and Alzheimer disease pathologies in 94 participants with msTBI and 94 participants without TBI matched by age, sex, education, and dementia status TBI from the Rush community-based cohorts. Six (3%) of brains showed the pathognomonic lesion of CTE-NC; only 3 of these had a history of msTBI. In contrast, ARTAG was common in older brains (gray matter ARTAG = 77%; white matter ARTAG = 54%; subpial ARTAG = 51%); there were no differences in severity, type, or distribution of ARTAG pathology with respect to history of msTBI. Furthermore, those with msTBI did not have higher levels of PHF-tau tangles density but had higher levels of amyloid-β load (Estimate = 0.339, SE = 0.164, p = 0.040). These findings suggest that CTE-NC is infrequent while ARTAG is common in the community and that both pathologies are unrelated to msTBI. The association of msTBI with amyloid-β, rather than with tauopathies suggests differential mechanisms of neurodegeneration in msTBI.

Mental Health Impacts of COVID-19: Does Prepandemic Cognition and Dementia Status Matter?

The coronavirus disease 2019 (COVID-19) pandemic disrupted daily life and led to sharp shocks in trends for various health outcomes. Although substantial evidence exists linking the pandemic and mental health outcomes and linking dementia and mental health outcomes, little evidence exists on how cognitive status may alter the impact of COVID-19 on mental health. We used prepandemic data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia study and 9 waves of data from the Real-Time Insights of COVID-19 in India study (N = 1182). We estimated associations between measures of prepandemic cognition (continuous cognition based on 22 cognitive tests, dementia status) and mental health measures during the pandemic (Patient Health Questionnaire [PHQ]-4 [9 time points], PHQ-9 [2 time points], Beck Anxiety Inventory [3 time points]), adjusting for age, gender, rural/urban residence, state, education, and prepandemic mental health. Summarizing across time points, PHQ-9 score was marginally or significantly associated with prepandemic cognition (PHQ-9 difference: -0.38 [-0.78 to 0.14] points per SD higher cognition; p = .06), and prepandemic dementia (PHQ-9 difference: 0.61 [0.11-1.13] points for those with dementia compared to no dementia; p = .02). Associations with BAI were null, whereas associations with PHQ-4 varied over time (p value for interaction = .02) and were strongest during the delta wave, when pandemic burden was highest. We present initial evidence that mental health impacts of COVID-19 or other acute stressors may be unequally distributed across strata of cognitive outcomes. In dynamically changing environments, those with cognitive impairment or dementia may be more vulnerable to adverse mental health outcomes.

Understanding the relationship between type-2 diabetes, MRI markers of neurodegeneration and small vessel disease, and dementia risk: a mediation analysis.

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk.The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels. Dementia status was assessed every 2 to 3 years, during up to 12 years of follow-up. Brain parenchymal fraction (BPF) and white matter hyperintensities volume (WMHV) were selected as markers of neurodegeneration and cerebral SVD respectively. We performed a mediation analysis of the effect of baseline BPF and WMHV (mediators) on the association between diabetes and dementia risk using linear and Cox models adjusted for age, sex, education level, hypertension, hypercholesterolemia, BMI, smoking and alcohol drinking status, APOE-ε4 status, and study site.At baseline, 8.8% of the participants had diabetes. Diabetes (yes vs. no) was associated with higher WMHV (βdiab = 0.193, 95% CI 0.040; 0.346) and lower BPF (βdiab=-0.342, 95% CI -0.474; -0.210), as well as with an increased risk of dementia over 12 years of follow-up (HRdiab=1.65, 95% CI 1.04; 2.60). The association between diabetes status and dementia risk was statistically mediated by higher WMHV (HRdiab=1.05, 95% CI 1.01; 1.11, mediated part = 10.8%) and lower BPF (HRdiab=1.12, 95% CI 1.05; 1.20, mediated part = 22.9%).This study showed that both neurodegeneration and cerebral SVD statistically explained almost 30% of the association between diabetes and dementia.

“VR is the future”: perspectives of healthcare professionals on virtual reality as a diagnostic tool for dementia status in primary care

BackgroundHealthcare professionals (HPs) hold critical perspectives on the barriers and facilitating factors for the implementation of virtual reality (VR) dementia diagnosis tools in the clinical setting. This study aims to explore HP perspectives regarding the clinical implementation of dementia diagnosis tools using VR platforms.MethodsAn exploratory qualitative interview study was carried out between July and September 2022. In-depth semi-structured interviews were conducted with HPs (n = 7) with clinical expertise in dementia diagnoses drawn from medicine, nursing and allied health practices. A hermeneutic phenomenological approach was used to frame the interview data across the dementia diagnosis pathway and application of new technology.ResultsHPs were on average 36.29 years old (SD = 11.56) with 11.85 years of experience (SD = 12.80, range:4–42). Analyses identified three main themes related to the contemporary methods of dementia diagnosis, dementia diagnosis and the medical landscape and HP perspectives on the usefulness and barriers of VR implementation. VR was considered an innovative prospect, with improved ecological validity compared to commonplace, current cognitive assessments. Concerns of time commitments, monetary costs and the validity of the new technology were identified as key barriers to implementation. Overall, implementation of a new diagnostic tool was considered a complex process.ConclusionsOur insight into general practice and nursing clinics can be supported to embed and integrate virtual reality platforms in primary care settings. Primary healthcare organizations require more funding and time related resources to produce a context in which VR tools could be implemented in a beneficial manner.

Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer’s pathology and dementia in the CFAS population-derived neuropathology cohort

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer’s disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer’s disease neuropathological change (ADNC). Temporal cortex (n = 99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection. Total cortical cholesterol was measured using the Amplex Red assay. HMGCR and SREBP2 proteins were predominantly expressed in pyramidal neurones, and in glia. Neuronal HMGCR did not vary with ADNC, oxidative stress, neuroinflammation or dementia status. Expression of HMGCR neuronal mRNA decreased with ADNC (p = 0.022) and increased with neuronal DNA damage (p = 0.049), whilst SREBP2 increased with ADNC (p = 0.005). High or moderate tertiles for cholesterol levels were associated with increased dementia risk (OR 1.44, 1.58). APOE ε4 allele was not associated with cortical cholesterol levels. ADNC is associated with gene expression changes that may impair cholesterol biosynthesis in neurones but not astrocytes, whilst levels of cortical cholesterol show a weak relationship to dementia status.

Racial and ethnic disparities in social isolation and 11-year dementia risk among older adults in the United States.

Social isolation has been implicated in the development of cognitive impairment, but research on this association remains limited among racial-ethnic minoritized populations. Our study examined the interplay between social isolation, race-ethnicity and dementia. We analyzed 11 years (2011-2021) of National Health and Aging Trends Study (NHATS) data, a prospective nationally representative cohort of U.S. Medicare beneficiaries aged 65 years and older. Dementia status was determined using a validated NHATS algorithm. We constructed a longitudinal score using a validated social isolation variable for our sample of 6,155 community-dwelling respondents. Cox regression determined how the interaction between social isolation and race-ethnicity was associated with incident dementia risk. Average longitudinal frequency of social isolation was higher among older Black (27.6%), Hispanic (26.6%) and Asian (21.0%) respondents than non-Hispanic White (19.1%) adults during the 11-year period (t = -7.35, p < .001). While a higher frequency of social isolation was significantly associated with an increased (approximately 47%) dementia risk after adjusting for sociodemographic covariates (adjusted hazard ratio [aHR] = 1.47, 95% CI [1.15, 1.88], p < .01), this association was not significant after adjusting for health covariates (aHR = 1.21, 95% CI [0.96, 1.54], p = .11). Race-ethnicity was not a significant moderator in the association between social isolation and dementia. Older adults from racial-ethnic minoritized populations experienced a higher longitudinal frequency of social isolation. However, race-ethnicity did not moderate the positive association observed between social isolation and dementia. Future research is needed to investigate the underlying mechanisms contributing to racial-ethnic disparities in social isolation and to develop targeted interventions to mitigate the associated dementia risk.

The Association Between Brain Metabolic Biomarkers Using 18F-FDG and Cognition and Vascular Risk Factors, as well as Its Usefulness in the Diagnosis and Staging of Alzheimer's Disease.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is valuable in Alzheimer's disease (AD) workup. To explore the effectiveness of 18F-FDG PET in differentiating and staging AD and associations between brain glucose metabolism and cognitive functions and vascular risk factors. 107 participates including 19 mild cognitive impairment (MCI), 38 mild AD, 24 moderate AD, 15 moderate-severe AD, and 11 frontotemporal dementia (FTD) were enrolled. Visual and voxel-based analysis procedures were utilized. Cognitive conditions, including 6 cognitive function scores and 7 single-domain cognitive performances, and vascular risk factors linked to hypertension, hyperlipidemia, diabetes, and obesity were correlated with glucose metabolism in AD dementia using age as a covariate. 18F-FDG PET effectively differentiated AD from FTD and also differentiated MCI from AD subtypes with significantly different hypometabolism (except for mild AD) (height threshold p < 0.001, all puncorr < 0.05, the same below). The cognitive function scores, notably Mini-Mental State Examination and Montreal Cognitive Assessment, correlated significantly with regional glucose metabolism in AD participants (all p < 0.05), whereas the single-domain cognitive performance and vascular risk factors were significantly associated with regional glucose metabolism in MCI patients (all p < 0.05). This study underlines the vital role of 18F-FDG PET in identifying and staging AD. Brain glucose metabolism is associated with cognitive status in AD dementia and vascular risk factors in MCI, indicating that 18F-FDG PET might be promising for predicting cognitive decline and serve as a visual framework for investigating underlying mechanism of vascular risk factors influencing the conversion from MCI to AD.

Influence of cognitive reserve on risk of depression and subsequent dementia: A large community-based longitudinal study.

Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival. Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression. Over a median follow-up of 12.96years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51-0.56]) and lower risk of post-depression dementia (0.55 [0.34-0.88]) or death (0.69 [0.55-0.88]) in middle-aged adults (aged <60years). In Laplace regression, the depression-free survival time was prolonged by 2.77 (2.58-2.96) years in participants with high compared to low CR. High CR is associated with lower risks of depression and subsequent transitions to dementia and death, particularly in middle age. High CR may prolong depression-free survival. Our findings highlight the importance of enhancing CR in the prevention and prognosis of depression.

Association of white matter hyperintensities with cognitive decline and neurodegeneration.

The relationship between white matter hyperintensities (WMH) and the core features of Alzheimer's disease (AD) remains controversial. Further, due to the prevalence of co-pathologies, the precise role of WMH in cognition and neurodegeneration also remains uncertain. Herein, we analyzed 1803 participants with available WMH volume data, extracted from the ADNI database, including 756 cognitively normal controls, 783 patients with mild cognitive impairment (MCI), and 264 patients with dementia. Participants were grouped according to cerebrospinal fluid (CSF) pathology (A/T profile) severity. Linear regression analysis was applied to evaluate the factors associated with WMH volume. Modeled by linear mixed-effects, the increase rates (Δ) of the WMH volume, cognition, and typical neurodegenerative markers were assessed. The predictive effectiveness of WMH volume was subsequently tested using Cox regression analysis, and the relationship between WMH/ΔWMH and other indicators such as cognition was explored through linear regression analyses. Furthermore, we explored the interrelationship among amyloid-β deposition, cognition, and WMH using mediation analysis. Higher WMH volume was associated with older age, lower CSF amyloid-β levels, hypertension, and smoking history (all p ≤ 0.001), as well as cognitive status (MCI, p < 0.001; dementia, p = 0.008), but not with CSF tau levels. These results were further verified in any clinical stage, except hypertension and smoking history in the dementia stage. Although WMH could not predict dementia conversion, its increased levels at baseline were associated with a worse cognitive performance and a more rapid memory decline. Longitudinal analyses showed that baseline dementia and positive amyloid-β status were associated with a greater accrual of WMH volume, and a higher ΔWMH was also correlated with a faster cognitive decline. In contrast, except entorhinal cortex thickness, the WMH volume was not found to be associated with any other neurodegenerative markers. To a lesser extent, WMH mediates the relationship between amyloid-β and cognition. WMH are non-specific lesions that are associated with amyloid-β deposition, cognitive status, and a variety of vascular risk factors. Despite evidence indicating only a weak relationship with neurodegeneration, early intervention to reduce WMH lesions remains a high priority for preserving cognitive function in the elderly.

Creating Cultural and Lifestyle Awareness About Dementia and Co-morbidities.

Dementia is a major health concern in society, particularly in the aging population. It is alarmingly increasing in ethnic minorities such as Native Americans, African Americans, Hispanics/Latinos, and to some extent Asians. With increasing comorbidities of dementia such as diabetes, obesity, and hypertension, dementia rates are expected to increase in the next decade and beyond. Understanding and treating dementia, as well as determining how to prevent it, has become a healthcare priority across the globe for all races and genders. Awareness about dementia and its consequences such as healthcare costs, and caregiver burden are immediate needs to be addressed. Therefore, it is high time for all of us to create awareness about dementia in society, particularly among Hispanics/Latinos, Native Americans, and African Americans. In the current article, we discuss the status of dementia, cultural, and racial impacts on dementia diagnosis and care, particularly in Hispanic populations, and possible steps to increase dementia awareness. We also discussed factors that need to be paid attention to, including, cultural & language barriers, low socioeconomic status, limited knowledge/education, religious/spiritual beliefs and not accepting modern medicine/healthcare facilities. Our article also covers both mental & physical health issues of caregivers who are living with patients with dementia, Alzheimer's disease, and Alzheimer's disease-related dementias. Most importantly, we discussed possible measures to create awareness about dementia, including empowering community advocacy, promoting healthy lifestyle choices, education on the impact of nutrition, encouraging community participation, and continued collaboration and evaluation of the success of dementia awareness.

Variation in direct healthcare costs to health system by residents living in longterm care facilities: a Registry of Senior Australians study.

ObjectiveThis study aimed to examine the national variation in government-subsidised healthcare costs of residents in long-term care facilities (LTCFs) and costs differences by resident and facility characteristics.MethodsA retrospective population-based cohort study was conducted using linked national aged and healthcare data of older people (≥65years) living in 2112 LTCFs in Australia. Individuals' pharmaceutical, out-of-hospital, hospitalisation and emergency presentations direct costs were aggregated from the linked healthcare data. Average annual healthcare costs per resident were estimated using generalised linear models, adjusting for covariates. Cost estimates were compared by resident dementia status and facility characteristics (location, ownership type and size).ResultsOf the 75,142 residents examined, 70% (N=52,142) were women and 53.4% (N=40,137) were living with dementia. The average annual healthcare cost (all costs in $A) was $9233 (95% CI $9150-$9295) per resident, with hospitalisation accounting for 47.2% of the healthcare costs. Residents without dementia had higher healthcare costs ($11,097, 95% CI $10,995-$11,200) compared to those with dementia ($7561, 95% CI $7502-$7620). Residents living in for-profit LTCFs had higher adjusted average overall annual healthcare costs ($11,324, 95% CI $11,185-$11,463) compared to those living in not-for-profit ($11,017, 95% CI $10,895-$11,139) and government ($9731, 95% CI $9365-$10,099) facilities.ConclusionsThe healthcare costs incurred by residents of LTCFs varied by presence of dementia and facility ownership. The variation in costs may be associated with residents' care needs, care models and difference in quality of care across LTCFs. As hospitalisation is the biggest driver of the healthcare costs, strategies to reduce preventable hospitalisations may reduce downstream cost burden to the health system.

Metabolic profiles associated with exposure to ambient particulate air pollution: findings from the Betula cohort.

Air pollution is a significant contributor to morbidity and mortality globally and has been linked to an increased risk of dementia. Previous studies within the Betula cohort in Northern Sweden have demonstrated associations between air pollution and dementia, as well as distinctive metabolomic profiles in dementia patients compared to controls. This study aimed to investigate whether air pollution is associated with quantitative changes in metabolite levels within this cohort, and whether future dementia status would modify this association. Both short-term and long-term exposure to air pollution were evaluated using high spatial resolution models and measured data. Air pollution from vehicle exhaust and woodsmoke were analyzed separately. Metabolomic profiling was conducted on 321 participants, including 58 serum samples from dementia patients and a control group matched for age, sex, and education level, using nuclear magnetic resonance spectroscopy. No statistically significant associations were found between any metabolites and any measures of short-term or long-term exposure to air pollution. However, there were trends potentially suggesting associations between both long-term and short-term exposure to air pollution with lactate and glucose metabolites. Notably, these associations were observed despite the lack of correlation between long-term and short-term air pollution exposure in this cohort. There were also tendencies for associations between air pollution from woodsmoke to be more pronounced in participants that would later develop dementia, suggesting a potential effect depending on urban/rural factors. While no significant associations were found, the trends observed in the data suggest potential links between air pollution exposure and changes in lactate and glucose metabolites. These findings provide some new insights into the link between air pollution and metabolic markers in a low-exposure setting. However, addressing existing limitations is crucial to improve the robustness and applicability of future research in this area. The pronounced associations in participants who later developed dementia may indicate an influence of urban/rural factors, warranting further investigation.

Trajectory of multimorbidity before dementia: A 24-year follow-up study.

Although the multimorbidity-dementia association has been widely addressed, little is known on the long-term trajectory of multimorbidity (TOM) in preclinical dementia. Based on the Health and Retirement Study, burden of multimorbidity was quantified with the total number of eight long-term conditions (LTC). Patterns of TOM before dementia diagnosis were investigated with mixed-effects models. In 1752 dementia cases and 5256 matched controls, cases showed higher and faster increasing predicted number of LTC than controls, with a significant case-control difference from 20 years prior to dementia diagnosis. Larger increases in number of LTC during preclinical phase of dementia were found in White participants, females, those whose age at dementia onset was younger, and those who were less educated. Our findings emphasize the faster accumulation of multimorbidity in prodromal dementia than in natural aging, as well as effect modifications by age and sex. TOM increased faster in prodromal dementia than in natural ageing.Patterns of TOM by dementia status diverged at 20 years before dementia diagnosis.Patterns of TOM were modified by age and sex.

Association between structural brain MRI abnormalities and epilepsy in older adults.

To determine the association between brain MRI abnormalities and incident epilepsy in older adults. Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status. Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3). This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.

Negative Wealth Shock and Cognitive Decline and Dementia in Middle-Aged and Older US Adults

As a financial hardship, negative wealth shock has been implicated in some adverse health outcomes. However, associations between negative wealth shock and cognitive decline and dementia have not been examined. To investigate whether negative wealth shock was associated with cognitive decline and incident dementia among middle-aged and older US adults. The Health and Retirement Study (HRS) is a prospective cohort study conducted biennially among US adults older than 50 years. Data from the HRS from calendar years 1996 to 2020 were analyzed from July 1 to 31, 2023. The final sample included 8082 participants with complete data of interest. Wealth status was quantified with questionnaires. Negative wealth shock was defined as a loss of 75% or more in total wealth over a 2-year period. Asset poverty was defined as zero or less total net wealth. Cognitive function was assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Dementia status was determined with TICS-m scores and proxy assessment. Among 8082 participants included (mean [SD] age, 63.7 [5.7] years; 4179 women [51.7%] and 3903 men [48.3%]; 1111 Black [13.7%], 6689 White [82.7%], and 282 other [3.5%]), 1441 developed incident dementia over a median follow-up time of 14 (IQR, 7-20) years. Compared with participants who had positive wealth without shock, those with negative wealth shock had accelerated cognitive decline (β coefficient, -0.014 [95% CI, -0.027 to -0.001]; P = .03) and increased risks of dementia (hazard ratio [HR], 1.27 [95% CI, 1.11-1.46]; P < .001). Higher dementia risks were also found in participants with asset poverty at baseline (HR, 1.61 [95% CI, 1.30-2.00]; P < .001). Associations were found in White participants (HR, 1.34 [95% CI, 1.14-1.58]; P < .001) and participants younger than 65 years (HR, 1.38 [95% CI, 1.13-1.68]; P = .001) but not in other races and ethnicities or those 65 years or older. In this cohort study, negative wealth shock was associated with accelerated cognitive decline and elevated risks of dementia among middle-aged and older US adults, with modifications by age and ethnicity. These findings should be confirmed by further prospective and interventional studies.

Clinical Profile and Prognosis of Dementia in Patients With Acute Decompensated Heart Failure - From the CURE-HF Registry.

Acute decompensated heart failure (ADHF) has a poor prognosis and common comorbidities may be contributory. However, evidence for the association between dementia and clinical outcomes in patients with is sparse and it requires further investigation into risk reduction.Methods and Results: We assessed the clinical profiles and outcomes of 1,026 patients (mean age 77.8 years, 43.2% female) with ADHF enrolled in the CURE-HF registry to evaluate the relationship between investigator-reported dementia status and clinical outcomes (all-cause death, cardiovascular (CV) death, non-CV death, and HF hospitalization) over a median follow-up of 2.7 years. In total, dementia was present in 118 (11.5%) patients, who experienced more drug interruptions and HF admissions due to infection than those without dementia (23.8% vs. 13.1%, P<0.01; 11.0% vs. 6.0%, P<0.01, respectively). Kaplan-Meier analysis revealed that dementia patients had higher mortality rates than those without dementia (log-rank P<0.001). After multivariable adjustment for demographics and comorbidities, dementia was significantly associated with an increased risk of death (adjusted hazard ratio, 1.43; 95% confidence interval, 1.06-1.93, P=0.02) and non-CV death (adjusted hazard ratio, 1.65; 95% confidence interval, 1.04-2.62, P=0.03), but no significant associations between dementia and CV death or HF hospitalization were observed (both, P>0.1). In ADHF patients dementia was associated with aggravating factors for HF admission and elevated risk of death, primarily non-CV death.