Joint modeling for cognitive trajectory and risk of dementia in the presence of death.
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ABSTRACT:
SUBMITTER: Yu B
PROVIDER: S-EPMC3036971 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
Publications
Joint modeling for cognitive trajectory and risk of dementia in the presence of death.
Biometrics 20090504 1
Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal aging. It has been known that cognitive impairment occurs long before the diagnosis of dementia. For individuals who develop dementia, it is important to determine the time when the rate of cognitive decline begins to accelerate and the subsequent gap time to dementia diagnosis. For normal aging individuals, it is also useful to understand the trajectory of cognitive function until their d ...[more]
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Project description:Background: Studies have shown select associations between cardiovascular risk factors and dementia, but mostly focused on Alzheimer's Disease (AD).Objective: We enhance these works by evaluating the relationship between the presence of cardiovascular risk factors and the rate of cognitive decline, measured using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SUM) on four common dementia subtypes (AD, dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD), as well as non-demented elderly individuals (normal)).Method: We used generalized linear mixed models with random intercepts to account for correlation at the patient and center levels for each dementia subtype adjusting for time since initial visit, baseline cognitive score, age, and demographic factors. The cardiovascular risk factors evaluated included body mass index, diabetes, years of smoking, atrial fibrillation, hypertension, and hypercholesterolemia.Results: Patients diagnosed with AD (n=1899), DLB (n=65), FTD (n=168), or VaD (n=13); or lacked cognitive impairment (normal) (n=3583) were evaluated using data from the National Alzheimer's Coordinating Centers. Cardiovascular risk factors were associated with select dementia subtypes including AD and FTD. Using MMSE and CDR-SUM, recent or active hypertension and hypercholesterolemia were associated with a slower cognitive decline for AD patients, while higher body mass index and years of smoking were associated with a slower cognitive decline for FTD patients. However, several cardiovascular factors demonstrated associations with more rapid cognitive decline.Conclusion: These results demonstrate disease specific associations and can provide clinicians guidance on predicted cognitive changes at the group level using information about cardiovascular risk factors.
| S-EPMC6162109 | biostudies-literature
Project description:ImportanceEvidence on the association of lifespan cognitive reserve (CR) with dementia is limited, and the strength of this association in the presence of brain pathologies is unknown.ObjectiveTo examine the association of lifespan CR with dementia risk, taking brain pathologies into account.Design, setting, and participantsThis study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years). After excluding 420 individuals who had prevalent dementia, missing data on CR, or dropped out, 1602 dementia-free adults were identified at baseline and evaluated to detect incident dementia. During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018.ExposuresInformation on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest).Main outcomes and measuresDementia was diagnosed following international criteria. Neuropathologic evaluations for Alzheimer disease and other brain pathologies were performed in autopsied participants. The association of lifespan CR with dementia or brain pathologies was estimated using Cox regression models or logistic regression.ResultsOf the 1602 included participants, 1216 (75.9%) were women, and the mean (SD) age was 79.6 (7.5) years. During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer disease-related dementia (22.3%). The multiadjusted hazards ratios (HRs) of dementia were 0.77 (95% CI, 0.59-0.99) for participants in the middle CR score tertile and 0.61 (95% CI, 0.47-0.81) for those in the highest CR score tertile compared with those in the lowest CR score tertile. In autopsied participants, CR was not associated with most brain pathologies, and the association of CR with dementia remained significant after additional adjustment for brain pathologies (HR, 0.60; 95% CI, 0.42-0.86). The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37-0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18-0.62).Conclusions and relevanceHigh lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.
| S-EPMC6628596 | biostudies-literature
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Project description:Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk.Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ?4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ?25 from 4 prospective cohort studies using Cox models adjusted for potential confounders.At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes.MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings.
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Project description:BackgroundCognitive health expectancy estimates the proportion of the lifespan that is lived in good cognitive health at the population level. A number of cardiovascular diseases have been identified to be risk factors for cognitive decline and dementia including diabetes, stroke, heart diseases and hypertension. The aim of this study was to examine how these cardiovascular conditions relate to cognitive health expectancy.MethodsLongitudinal data were obtained from the US Health and Retirement Study. Multistate modelling was used to estimate total life expectancy (LE), cognitive impairment free life expectancy (CIFLE) and years spent with cognitive impairment (CILE) across self-reported diabetes, hypertension, heart problems and stroke. Individual and cumulative effects of multiple cardiovascular conditions were examined.ResultsThe presence of cardiovascular disease was associated with a 5- to 9-year decrease in LE and 4- to 8-year decrease in CIFLE at age 55. The outcomes varied in a hierarchical fashion by cardiovascular condition. Relative to other conditions, individuals with stroke had the shortest LE and CIFLE. Analysis of multiple cardiovascular risk factors revealed that each additional cardiovascular condition was associated with an exponential decrease in LE and CIFLE.ConclusionsHaving a cardiovascular condition is associated with a lower CIFLE and higher proportion of life lived with cognitive impairment. However, the outcomes vary depending on the type of cardiovascular condition. Reducing incidence of stroke and minimising exposure to multiple cardiovascular risk factors may be beneficial in helping to improve population estimates of cognitive health expectancy.
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Project description:ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1-42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1-42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP-43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1-42 also predict some measures of disease aggressiveness in frontotemporal dementia.
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Project description:We investigated the association between five factor model personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and risk of dementia, cognitive impairment not dementia (CIND), and conversion from CIND to dementia in a large national cohort. Participants from the Health and Retirement Study (N > 10,000) completed a personality scale in 2006-2008 and their cognitive status was tracked for up to 8 years using the modified Telephone Interview for Cognitive Status (TICSm). Adjusting for age, sex, education, race, and ethnicity, lower conscientiousness and agreeableness and higher neuroticism were independently associated with increased risk of dementia. These associations remained significant after adjusting for other risk factors for dementia, including income, wealth, smoking, physical inactivity, obesity, diabetes, hypertension, and blood biomarkers. These associations were not modified by age, sex, race, ethnicity, and education, suggesting that the associations of personality with risk of dementia were similar across demographic groups. Neuroticism and conscientiousness were also associated with risk of CIND. Low conscientiousness predicted conversion from CIND to dementia. Using brief assessments of personality and cognition, we found robust evidence that personality is associated with risk of cognitive impairment and dementia in a large national sample.
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