Summary Background Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a ...population of community-dwelling older people. Methods In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70–78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score ALDS) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771. Findings Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6·7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio HR 0·92, 95% CI 0·71–1·19; p=0·54). Mean ALDS scores measured during follow-up did not differ between groups (85·7 SD 6·8 in the intervention group and 85·7 7·1 in the control group; adjusted mean difference −0·02, 95% CI −0·38 to 0·42; p=0·93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0·98, 95% CI 0·80–1·18; p=0·81). Incident cardiovascular disease did not differ between groups (273 19% of 1469 participants in the intervention group and 228 17% of 1307 participants in the control group; HR 1·06, 95% CI 0·86–1·31; p=0·57). Interpretation A nurse-led, multidomain intervention did not result in a reduced incidence of all-cause dementia in an unselected population of older people. This absence of effect might have been caused by modest baseline cardiovascular risks and high standards of usual care. Future studies should assess the efficacy of such interventions in selected populations. Funding Dutch Ministry of Health, Welfare and Sport; Dutch Innovation Fund of Collaborative Health Insurances; and Netherlands Organisation for Health Research and Development.
IMPORTANCE: Fear of dementia is pervasive in older people with cognitive concerns. Much research is devoted to finding prognostic markers for dementia risk. Studies suggest apathy in older people may ...be prodromal to dementia and could be a relevant, easily measurable predictor of increased dementia risk. However, evidence is fragmented and methods vary greatly between studies. OBJECTIVE: To systematically review and quantitatively synthesize the evidence for an association between apathy in dementia-free older individuals and incident dementia. DATA SOURCES: Two reviewers conducted a systematic search of Medline, Embase, and PsychINFO databases. STUDY SELECTION: Inclusion criteria were (1) prospective cohort studies, (2) in general populations or memory clinic patients without dementia, (3) with clear definitions of apathy and dementia, and (4) reporting on the association between apathy and incident dementia. DATA EXTRACTION AND SYNTHESIS: PRISMA and MOOSE guidelines were followed. Data were extracted by 1 reviewer and checked by a second. MAIN OUTCOMES AND MEASURES: Main outcomes were pooled crude risk ratios, maximally adjusted reported hazard ratios (HR), and odds ratios (OR) using DerSimonian-Laird random effects models. RESULTS: The mean age of the study populations ranged from 69.2 to 81.9 years (median, 71.6 years) and the percentage of women ranged from 35% to 70% (median, 53%). After screening 2031 titles and abstracts, 16 studies comprising 7365 participants were included. Apathy status was available for 7299 participants. Studies included populations with subjective cognitive concerns (n = 2), mild cognitive impairment (n = 11), cognitive impairment no dementia (n = 1), or mixed cognitive and no cognitive impairment (n = 2). Apathy was present in 1470 of 7299 participants (20.1%). Follow-up ranged from 1.2 to 5.4 years. In studies using validated apathy definitions (n = 12), the combined risk ratio of dementia for patients with apathy was 1.81 (95% CI, 1.32-2.50; I2 = 76%; n = 12), the hazard ratio was 2.39 (95% CI, 1.27-4.51; I2 = 90%; n = 7), and the odds ratio was 17.14 (95% CI, 1.91-154.0; I2 = 60%; n = 2). Subgroup analyses, meta-regression, and individual study results suggested the association between apathy and dementia weakened with increasing follow-up time, age, and cognitive impairment. Meta-regression adjusting for apathy definition and follow-up time explained 95% of heterogeneity in mild cognitive impairment. CONCLUSIONS AND RELEVANCE: Apathy was associated with an approximately 2-fold increased risk of dementia in memory clinic patients. Moderate publication bias may have inflated some of these estimates. Apathy deserves more attention as a relevant, cheap, noninvasive, and easily measureable marker of increased risk of incident dementia with high clinical relevance, particularly because these vulnerable patients may forgo health care.
IMPORTANCE: The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown. OBJECTIVE: To investigate whether the association between SBP and dementia risk is ...U-shaped and whether age and comorbidity play a role in this association. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021. EXPOSURES: Baseline systolic BP. MAIN OUTCOMES AND MEASURES: All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised or Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines. RESULTS: The study analyzed 7 cohort studies with a total of 17 286 participants, among whom 10 393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P = .001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 95% CI, 152-178 mm Hg to 170 95% CI, 160-260 mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P < .001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P = .03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P < .001) and 166 mm Hg (95% CI, 154-260 mm Hg; P = .02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct. CONCLUSIONS AND RELEVANCE: This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.
To evaluate the effects of nurse-led multifactorial care to prevent disability in community-living older people.
In a cluster randomized trail, 11 practices (n = 1,209 participants) were randomized ...to the intervention group, and 13 practices (n = 1,074 participants) were randomized to the control group. Participants aged ≥ 70 years were at increased risk of functional decline based on a score ≥ 2 points on the Identification of Seniors at Risk- Primary Care, ISAR-PC. Participants in the intervention group received a systematic comprehensive geriatric assessment, and individually tailored multifactorial interventions coordinated by a trained community-care registered nurse (CCRN) with multiple follow-up home visits. The primary outcome was the participant's disability as measured by the modified Katz activities of daily living (ADL) index score (range 0-15) at one year follow-up. Secondary outcomes were health-related quality of life, hospitalization, and mortality.
At baseline, the median age was 82.7 years (IQR 77.0-87.1), the median modified Katz-ADL index score was 2 (IQR 1-5) points in the intervention group and 3 (IQR 1-5) points in the control group. The follow-up rate was 76.8% (n = 1753) after one year and was similar in both trial groups. The adjusted intervention effect on disability was -0.07 (95% confidence interval -0.22 to 0.07; p = 0.33). No intervention effects were found for the secondary outcomes.
We found no evidence that a one-year individualized multifactorial intervention program with nurse-led care coordination was better than the current primary care in community-living older people at increased risk of functional decline in The Netherlands.
Netherlands Trial Register NTR2653.
Older people with subjective memory complaints (SMC) and Instrumental Activities of Daily Living impairments (IADL-I) have an increased risk of developing dementia. Previous reports suggest that the ...predictive value of SMC and IADL-I may differ between sexes, leaving possible consequences for personalized risk prediction and prognosis. However, none of these studies addressed the competing risk of death, which may substantially differ between sexes.
We investigated sex-differences in the association between IADL-I, SMC, and incident dementia and mortality as competing risk.
3,409 community-dwelling older people without dementia (mean age 74.3±2.5), were followed for 6.7 years (median). Baseline SMC were assessed using the 15-item Geriatric Depression Scale memory question, and IADL-I using the Academic Medical Center Linear Disability Score. Potential sex-differences in the predictive value of SMC and IADL-I were assessed using Cox regression models with an interaction term for sex.
HRs for isolated SMC and SMC + IADL-I and risk of dementia were higher in women (HR: 2.02, 95% CI = 0.91-4.46, p = 0.08; HR:2.85, 95% CI = 1.65-4.91, p < 0.001) than in men (HR:1.52, 95% CI = 0.86-2.69, p = 0.18; HR:1.24, 95% CI = 0.62-2.49, p = 0.54), but these sex-differences were not significant. Conversely, HRs for isolated IADL-I and risk of mortality were higher in men (HR:1.56, 95% CI = 1.18-2.05, p = 0.002) than in women (HR:1.14, 95% CI = 0.80-1.62, p = 0.48), but again, these sex-differences were not significant.
The predictive value of SMC and IADL-I for the risk of dementia and mortality was not significantly modified by sex. However, the competing risk of death for these factors differed considerably between men and women, suggesting it is an essential factor to consider when comparing sex-differences in IADL/dementia risk.
Although web-based interventions have been promoted for cardiovascular risk management over the past decade, there is limited evidence for effectiveness of these interventions in people older than 65 ...years. The healthy ageing through internet counselling in the elderly (HATICE) trial aimed to determine whether a coach-supported internet intervention for self-management can reduce cardiovascular risk in community-dwelling older people.
This prospective open-label, blinded endpoint clinical trial among people age 65 years or over at increased risk of cardiovascular disease randomly assigned participants in the Netherlands, Finland, and France to an interactive internet intervention stimulating coach-supported self-management or a control platform. Primary outcome was the difference from baseline to 18 months on a standardised composite score (Z score) of systolic blood pressure, LDL cholesterol, and body-mass index (BMI). Secondary outcomes included individual risk factors and cardiovascular endpoints. This trial is registered with the ISRCTN registry, 48151589, and is closed to accrual.
Among 2724 participants, complete primary outcome data were available for 2398 (88%). After 18 months, the primary outcome improved in the intervention group versus the control group (0·09 vs 0·04, respectively; mean difference −0·05, 95% CI −0·08 to −0·01; p=0·008). For individual components of the primary outcome, mean differences (intervention vs control) were systolic blood pressure −1·79 mm Hg versus −0·67 mm Hg (−1·12, −2·51 to 0·27); BMI −0·23 kg/m2 versus −0·08 kg/m2 (−0·15, −0·28 to −0·01); and LDL −0·12 mmol/L versus −0·07 mmol/L (−0·05, −0·11 to 0·01). Cardiovascular disease occurred in 30 (2·2%) of 1382 patients in the intervention versus 32 (2·4%) of 1333 patients in the control group (hazard ratio 0·86, 95% CI 0·52 to 1·43).
Coach-supported self-management of cardiovascular risk factors using an interactive internet intervention is feasible in an older population, and leads to a modest improvement of cardiovascular risk profile. When implemented on a large scale this could potentially reduce the burden of cardiovascular disease.
European Commission Seventh Framework Programme.
Previous findings suggest that apathy symptoms independently of depressive symptoms measured using the Geriatric Depression Scale (GDS) are associated with cardiovascular disease (CVD) in older ...individuals.
To study whether apathy and depressive symptoms in older people are associated with future CVD, stroke, and mortality using individual patient-data meta-analysis.
Medline, Embase, and PsycInfo databases up to September 3, 2013, were systematically searched without language restrictions. We sought prospective studies with older (mean age ≥65 years) community-dwelling populations in which the GDS was employed and subsequent stroke and/or CVD were recorded to provide individual participant data. Apathy symptoms were defined as the three apathy-related subitems of the GDS, with depressive symptoms the remaining items. We used myocardial infarction (MI), stroke, and all-cause mortality as main outcomes. Analyses were adjusted for age, sex, and MI/stroke history. An adaptation of the Newcastle-Ottawa scale was used to evaluate bias. Hazard ratios were calculated using one-stage random-effect Cox regression models.
Of the 52 eligible studies, 21 (40.4%) were included, comprising 47,625 older people (mean age standard deviation 74 7.4 years), over a median follow-up of 8.8 years. Participants with apathy symptoms had a 21% higher risk of MI (95% confidence interval CI 1.08-1.36), a 37% higher risk of stroke (95% CI 1.18-1.59), and a 47% higher risk of all-cause mortality (95% CI 1.38-1.56). Participants with depressive symptoms had a comparably higher risk of stroke (HR 1.36, 95% CI 1.18-1.56) and all-cause mortality (HR 1.44, 95% CI 1.35-1.53), but not of MI (HR 1.08, 95% CI 0.91-1.29). Associations for isolated apathy and isolated depressive symptoms were comparable. Sensitivity analyses according to risk of bias yielded similar results.
Our findings stress the clinical importance of recognizing apathy independently of depressive symptoms, and could help physicians identify persons at increased risk of vascular disease.
To systematically review and synthesize the evidence on differential associations between antihypertensive medication (AHM) classes and the risk of incident dementia.
Systematic review and random ...effects frequentist network meta-analysis. Embase, MEDLINE, and the Cochrane library were searched from origin to December 2019.
Randomized controlled trials (RCTs) and prospective cohort studies that compared associations of different AHM classes with incident all-cause dementia and/or Alzheimer's disease over at least 1 year of follow-up.
All cause dementia and/or Alzheimer's disease.
Fifteen observational studies and 7 RCTs were included. Data on AHM classes were available for 649,790 participants and dementia occurred in 19,600 (3.02%). Network meta-analysis showed that in observational studies, treatment with either calcium channel blockers (CCBs) or angiotensin II receptor blockers (ARBs) was associated with lower dementia risks than treatment with other antihypertensives: CCBs vs angiotensin converting enzyme inhibitors (ACE inhibitors) (HR=0.84, 95% CI 0.74-0.95), beta blockers (HR=0.83, 95% CI 0.73-0.95) and diuretics (HR=0.89, 95% CI 0.78-1.01) and ARBs vs ACE inhibitors (HR=0.88, 95% CI 0.81-0.97), beta blockers (HR=0.87, 95% CI 0.77-0.99), and diuretics (HR=0.93, 95% CI 0.83-1.05). There were insufficient RCTs to create a robust network based on randomized data alone.
Recommending CCBs or ARBs as preferred first-line antihypertensive treatment may significantly reduce the risk of dementia. If corroborated in a randomized setting, these findings reflect a low-cost and scalable opportunity to reduce dementia incidence worldwide.
Socioeconomic status (SES) and ethnicity are both important determinants of hypertension prevalence and control rates but their separate contribution is unknown. We assessed the association of SES ...with hypertension prevalence, awareness, treatment and control, and whether this differs between ethnic groups.
We used baseline data from the Healthy Life in an Urban Setting (HELIUS) study, a multiethnic population-based cohort study, including 18 106 participants (84% of the total cohort) of Dutch (n = 4262), African Surinamese (n = 3732), Moroccan (n = 2902), Turkish (n = 2694), South-Asian Surinamese (n = 2664) and Ghanaian (n = 1947) descent with data on SES and hypertension status.
Regardless of ethnicity, lower SES was associated with higher hypertension prevalence, especially in participants with no education compared with those with higher levels of education OR 2.29 (2.05-2.56). There was an inverse association between SES and hypertension treatment with the strongest association for lower compared with higher educated participants OR 1.63 (1.39-1.90). In addition, lower SES was associated with lower hypertension control with the strongest association for participants with the lowest compared with the highest occupational level OR 0.76 (0.60-0.95). The association between educational level and treatment but not the other SES- or hypertension-indicators, was influenced by ethnicity, with lower educated Dutch and African Surinamese having higher ORs for hypertensive treatment Dutch OR 1.98 (1.43-2.76); African Surinamese OR 1.44 (1.10-1.89).
SES, in particular education, impacts hypertension treatment in the Netherlands, whereas the association of specific SES parameters with hypertension indicators differ across ethnic groups. Further exploration is needed on how sociocultural beliefs and behaviours may differentially affect blood pressure control across ethnic minority populations.
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