Agitation and impulsivity in mid and late life as possible risk markers for incident dementia.
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ABSTRACT:
SUBMITTER: Bateman DR
PROVIDER: S-EPMC7507499 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Agitation and impulsivity in mid and late life as possible risk markers for incident dementia.
Bateman Daniel R DR Gill Sascha S Hu Sophie S Foster Erin D ED Ruthirakuhan Myuri T MT Sellek Allis F AF Mortby Moyra E ME Matušková Veronika V Ng Kok Pin KP Tarawneh Rawan M RM Freund-Levi Yvonne Y Kumar Sanjeev S Gauthier Serge S Rosenberg Paul B PB Ferreira de Oliveira Fabricio F Devanand D P DP Ballard Clive C Ismail Zahinoor Z
Alzheimer's & dementia (New York, N. Y.) 20200906 1
To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre-dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cog ...[more]
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Project description:We examined the interactions between educational attainment and genetic susceptibility on dementia risk among adults over 60 years old. A total of 174,161 participants were free of dementia at baseline. The APOE ε4-related genetic risk was evaluated by the number of APOE ε4 alleles. The overall genetic susceptibility of dementia was evaluated by polygenetic risk score (PRS). Cox proportional hazards models were used to estimate the association between educational attainment and incident dementia. During a median of 8.9 years of follow-up, a total of 1482 incident cases of dementia were documented. After adjustment for covariates, we found that low education attainment was significantly associated with higher dementia risk in the APOE ε4 carriers, and such relation appeared to be stronger with the increasing number of ε4 alleles. In contrast, educational attainment was not associated with dementia risk in non-APOE ε4 carriers (P for multiplicative interaction = 0.006). In addition, we observed that the dementia risk associated with a combination of low educational attainment and high APOE ε4-related genetic risk was more than the addition of the risk associated with each of these factors (P for additive interaction < 0.001). We found similar significant interactions between educational attainment and PRS on both the multiplicative and additive scales on the dementia risk, mainly driven by the APOE genotype. These data indicate that higher educational attainment in early life may attenuate the risk for dementia, particularly among people with high genetic predisposition.
| S-EPMC9213617 | biostudies-literature
Project description:BackgroundActivated Vitamin D has anti-inflammatory properties and adequate 25-hydroxyvitamin D [25(OH)D] concentrations may be important for neurocognitive function and protection against neurologic injury. We examined whether mid-life 25(OH) D concentrations were associated with later-life performance on neuropsychological testing, functional ability, depressive symptoms, and incident dementia.MethodsWe studied 13,039 white and black ARIC participants who had serum 25(OH) D measured mid-life at visit 2 (1990-1992). Over the next ~ 20 years through visit 5 (2011-2013), participants underwent 3 additional in-person visits, annual telephone calls, and hospitalization surveillance. An extensive battery of neuropsychological outcomes were assessed at visit 5 using standardized protocols. Incident dementia was ascertained through a formal algorithm that included data from in-person cognitive testing, telephone interviews, hospital discharge codes, and death certificate codes. Diagnoses of dementia were adjudicated by expert clinician committee. For the primary cognitive analyses, we imputed for missing covariates and outcomes and used linear regression to evaluate non-concurrent cross-sectional associations of mid-life 25(OH) D (visit 2) with late-life neuropsychological outcomes (visit 5). We also used Cox regression models to examine associations of mid-life 25(OH) D and incident dementia.ResultsIn mid-life, the mean (SD) age of participants was 57 (6) years, 57% were women, and 24% black. Mean (SD) 25(OH) D was 24.3 (8.6) ng/mL; 33% had deficient (< 20 ng/mL), 44% intermediate (20- < 30 ng/mL), and 23% sufficient (≥30 ng/mL) 25(OH) D concentrations. Association between mid-life 25(OH) D and late-life performance on neuropsychological testing were mostly null. There was no significant association with functional ability or depressive symptoms. Results were similar in a sensitivity analysis using complete-case data (no imputation). However, after a median follow-up of 20 years, low 25(OH) D concentrations were associated with increased risk for incident dementia (p = 0.01 for trend across categories), with HR of 1.26 (95% CI 1.06, 1.49) for participants with deficient 25(OH) D, compared to sufficient concentrations.ConclusionIn this community cohort, mid-life serum 25(OH) D concentrations were associated with incident dementia but not with performance on neuropsychological testing, functional ability, or depressive symptoms, 20 years later. Whether serum 25(OH) D concentrations are causally related to dementia or confounded by poorer health status remains uncertain.Trial registrationRegistered on clinicaltrials.gov NCT00005131 .
| S-EPMC6805504 | biostudies-literature
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| S-EPMC9260147 | biostudies-literature
Project description:BackgroundSleep medications may contribute to dementia development or indicate sleep disturbances that are markers of or contributors to neurologic disease. The objective of this study was to examine the use of sleep medications and incident dementia in a community-based cohort of older adults. We hypothesize late-life sleep medication use is associated with a greater risk of dementia.MethodsThe Atherosclerosis Risk in Communities (ARIC) study is an ongoing community-based cohort study. ARIC participants taking barbiturates, benzodiazepines, antidepressants, non-benzodiazepine receptor agonists (Z-drugs), or other hypnotics in 2011-2013 were categorized as sleep medication users. Participants were followed through 2019 for incident dementia. Logistic regression propensity scores were used to match sleep medication users with nonusers (1:2). Cox proportional hazards regression models were used to estimate hazard ratios (HR) for time to dementia diagnosis with adjustment for demographics, lifestyle characteristics, and cardiovascular risk factors.ResultsOne-quarter of the eligible ARIC participants used sleep medications. In the matched sample (N = 4 197; 69% female; mean age 75.3 + 5.0 years), 632 dementia cases were ascertained over a median follow-up of 6.5 years. In the fully adjusted model, sleep medication use compared to nonuse was associated with a 48% greater risk of dementia (HR: 1.48; 95% confidence interval (CI): 1.26-1.74).ConclusionTo expand on these findings, studies with longer follow-up and earlier assessment of sleep medication use are needed. Furthermore investigation of the potential dose-response association of multiple sleep medications and the potential causal role of sleep medications in the development of dementia may be clinically meaningful.
| S-EPMC9977227 | biostudies-literature
Project description:ImportanceThe association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged hypertension may be associated with poor cognitive outcomes.ObjectiveTo examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline.Design, setting, and participantsThe Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017.ExposuresFive groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5.Main outcomes and measuresPrimary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation.ResultsAmong 4761 participants (2821 [59%] women; 979 [21%] black race; visit 5 mean [SD] age, 75 [5] years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio [HR], 1.49 [95% CI, 1.06-2.08]) and in the midlife hypertension and late-life hypotension group (HR, 1.62 [95% CI, 1.11-2.37]) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 [95% CI, 1.17-1.71]). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 [95% CI, 1.01-2.69]). There was no significant association of BP patterns with late-life cognitive change.Conclusions and relevanceIn this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.
| S-EPMC6692677 | biostudies-literature
Project description:BackgroundA diagnosis of dementia in middle-aged and elder people is often complicated by physical frailty and comorbid neuropsychiatric symptoms (NPSs). Previous studies have identified NPSs as a risk factor for dementia. The aim of this study was to figure out to what extent individual NPS and certain demographic factors increased the risk of dementia in middle-aged and senior psychiatric inpatients.MethodsOne hundred twenty-seven middle-aged and senior patients admitted to psychiatric wards for late-onset (age ≥ 50 years) psychiatric symptoms were included and categorized into dementia or non-demented psychiatric disorders (NDPD). The patients' demographic information and medical records were collected during the first hospitalization and subjected to statistical analyses.Results41.73% of the registered psychiatric inpatients were diagnosed as dementia in which Alzheimer's disease (AD) was the dominant subtype. The NDPD group consisted of nine individual diagnoses, except for schizophrenia. The frequencies of dementia inpatients increased with first episode age while that of NDPD inpatients decreased with first episode age. In the enrolled inpatients, most of dementia patients were males while females accounted for a higher proportion of NDPD patients. 58.49% of enrolled dementia inpatients presented cognitive deficit (CD) as the initial symptom while the remaining 41.51% showed NPS as initial symptom. Of the 12 NPSs, agitation and apathy greatly and significantly increased risk of dementia in psychiatric inpatients with late-onset psychiatric symptoms.ConclusionsThese results added evidence that the demented patients admitted to psychiatric ward are more likely to be male, older first episode age, and have characteristic NPS including aberrant motor behavior (AMB), hallucinations, agitation, irritability and apathy. Further, this study emphasized the importance of agitation and apathy of NPSs functioning as risk factors of dementia in these inpatients.
| S-EPMC8080316 | biostudies-literature
Project description:BackgroundEpidemiologic data supporting the association of accumulated inflammation from mid- to late life with late-life risk of cardiac dysfunction and heart failure (HF) is limited.Methods and resultsAmong 4011 participants in the Atherosclerosis Risk in Communities study who were free of prevalent cardiovascular disease at study Visit 5, accumulated inflammation was defined as time-averaged high-sensitivity c-reactive protein (hsCRP) over 3 visits spanning 1990 to 2013. Associations with left ventricular (LV) function at Visit 5 and with incident adjudicated HF post Visit 5 were assessed using linear and Cox regression, adjusting for demographics and comorbidities. Higher accumulated hsCRP was associated with greater LV mass index, lower e', higher E/e', and higher adjusting for demographics (all P ≤0.01), but only with higher pulmonary artery systolic pressure after adjustment for comorbidities (P = 0.024). At 5.3 ± 1.2 year follow-up, higher accumulated hsCRP was associated with greater risk of incident HF (HR 1.31 [95% CI 1.18-1.47], P < 0.001), HFrEF (1.26 [1.05-1.52], P = 0.01), and HFpEF (1.30 [1.11-1.53], P = 0.001) in demographic-adjusted models, but not after adjustment for comorbidities (all P > 0.10). Only Visit 5 hsCRP remained associated with incident HF (1.12 [1.02-1.24], P = 0.02) after full adjustment.ConclusionsGreater accumulated inflammation is associated with worse LV function and heightened HF risk in late-life. These relationships are attenuated after adjusting for HF risk factors.
| S-EPMC8823406 | biostudies-literature
Project description:Growing evidence relates body mass index (BMI) to poorer health outcomes; however, results across studies associating BMI and dementia are conflicting. A total of 3,632 Framingham Offspring participants aged 20 to 60 years at their second health examination (1979-1983) were included in this study, with 190 cases of incident dementia identified by 2017. Cox proportional hazards regression models were fitted to investigate the association of BMI at each of their 8 exams as a baseline for dementia risk and the associations between obesity and dementia across age groups. Spline models were fitted to investigate nonlinear associations between BMI and dementia. Each 1-unit increase in BMI at ages 40-49 years was associated with higher risk of dementia, but with lower risk after age 70 years. Obesity at ages 40-49 years was associated with higher risk of dementia. Overall, the relationship between BMI and dementia risk was heterogeneous across the adult age range. Monitoring BMI at different ages might mediate risk for dementia across an individual's lifetime.
| S-EPMC8796797 | biostudies-literature
Project description:BackgroundVery few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia.Methods and findingsThis cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)'s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p < 0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses.ConclusionsIn this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia.
| S-EPMC7737898 | biostudies-literature
Project description:ObjectiveTo develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.MethodsSubjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.ResultsSubjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.ConclusionsThe late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.
| S-EPMC2715571 | biostudies-literature