scholarly journals The Effect of Multidomain Interventions on Global Cognition, Symptoms of Depression and Apathy – A Pooled Analysis of Two Randomized Controlled Trials

Author(s):  
M.G.H.E. den Brok ◽  
M.P. Hoevenaar-Blom ◽  
N. Coley ◽  
S. Andrieu ◽  
J. van Dalen ◽  
...  

BACKGROUND: Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies, and have been targeted by multidomain interventions. Objectives: We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses. Design: Pooled analysis of individual participant data. Setting: Prevention of Dementia by Intensive Vascular Care trial (preDIVA) and Multidomain Alzheimer Preventive Trial (MAPT). Participants: Community-dwelling individuals, free from dementia at baseline. Intervention: Multidomain interventions focused on cardiovascular and lifestyle related risk factors. Measurements: Data on cognitive functioning, depressive symptoms and apathy were collected at baseline, 2 years and 3-4 years of follow-up as available per study. We analyzed crude scores with linear mixed models for overall cognitive function (Mini Mental State Examination [MMSE]), and symptoms of depression and apathy (15-item Geriatric Depression Scale). Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE <26, history of hypertension, and history of stroke, myocardial infarction and/or diabetes mellitus. Results: We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in cognitive functioning scores and symptoms of depression and apathy scores in the pooled study population. The MMSE declined less in the intervention groups in those with MMSE <26 at baseline (N=250; MD: 0.84; 95%CI: 0.15 to 1.54; p<0.001). Conclusions: We found no conclusive evidence that multidomain interventions reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. Our results suggest that these interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions.

Stroke ◽  
2021 ◽  
Author(s):  
Jessica W. Lo ◽  
John D. Crawford ◽  
David W. Desmond ◽  
Hee-Joon Bae ◽  
Jae-Sung Lim ◽  
...  

Background and Purpose: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. Methods: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. Results: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th–75th percentile: 1.21–4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (−0.053 SD/year [95% CI, −0.073 to −0.033]; P <0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=−0.078 SD/year [95% CI, −0.11 to −0.045]; P <0.001 for global cognition in a subgroup analysis). Conclusions: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.


2017 ◽  
Vol 30 (6) ◽  
pp. 843-862 ◽  
Author(s):  
Rosalba Hernandez ◽  
Elaine Cheung ◽  
Minli Liao ◽  
Seth W. Boughton ◽  
Lisett G. Tito ◽  
...  

Objective: We examined the association between depressive symptoms and cognitive functioning in older Hispanics/Latinos enrolled in an exercise intervention. Method: We analyzed baseline, 1-year, and 2-year in-person interview data collected from Hispanics/Latinos aged ≥60 years participating in an exercise intervention across 27 senior centers ( N = 572). Results: Mean age was 73.13 years; 77% female. At baseline, older adults screening positive for depression were 1.58 times more likely to experience cognitive impairment ( p = .04); controlling for demographics and comorbid chronic conditions. Compared to peers with little to no depressive symptoms, lower cognitive functioning scores were evident at each follow-up assessment point where elevated depressive symptoms were present, but baseline depression was not associated with cognitive function in longitudinal analyses. Discussion: In older Hispanics/Latinos enrolled in an exercise intervention, though baseline depression did not predict cognitive function over time, elevated symptoms of depression were associated with greater cognitive impairment at every point in this study.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Yoshitaka Murakami ◽  
Tomonori Okamura ◽  
Katsuyuki Miura ◽  
Hirotsugu Ueshima ◽  

Introduction: Individual participant data (IPD) meta-analyses involve participant-level data from multiple cohort studies. However, these cohorts have different periods (years) of follow-up, target regions, and distributions of risk factors (including patient age). It remains unclear if these variations affect the heterogeneity of absolute/relative measures of mortality in cardiovascular disease (CVD), stroke, and coronary heart disease (CHD) among cohorts. Hypothesis: There is diverse heterogeneity in absolute measures of mortality, but negligible heterogeneity in relative measures among cohorts in IPD meta-analyses. Methods: The Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN) study is an IPD meta-analysis of cardiovascular epidemiology. This project comprises 14 cohort studies with 105,945 Japanese subjects (total CVD deaths: 5,314). First, we examined the correlation between the follow-up periods of the baseline surveys and multivariate-adjusted mortality rates (CVD, stroke, and CHD) among the cohorts. Next, we estimated the cohort-specific mortality rates that adjusted for the stated follow-up periods, regions, age, and other risk factors using Poisson regression. Finally, we explored the heterogeneity of multivariate-adjusted mortality rates, mortality rate ratios, and rate ratios of 10-mmHg increases in systolic blood pressure using Higgins’s I 2 , which measures heterogeneity in meta-analyses. Results: High correlations were observed between the stated follow-up periods of the cohorts and their mortality rates (CVD [men, -0.70; women, -0.79], stroke [men, -0.65; women, -0.73], CHD [men, -0.24; women, -0.89]). In the multivariate-adjusted mortality rates, we observed clear heterogeneity in mortality rates among the cohorts (CVD [I 2 : men, 98.6%; women, 99.3%], stroke [I 2 : men, 98.5%; women, 98.3%], and CHD [I 2 : men, 98.2%; women 92.4%]). In the rate ratio comparison of 10-mmHg increases in systolic blood pressure, no heterogeneity was detected among the cohorts (CVD [I 2 : men, 0.0%; women, 17.9%]). Our results indicated that the ratio measure, which shows the magnitude of each risk factor, was stable even in the heterogeneity of absolute measures. Conclusions: A clear heterogeneity in mortality was observed in absolute measures, but not in relative measures, among cohorts after adjusting for the periods of follow-up, regions, and other risk factors.


2006 ◽  
Vol 189 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Jae-Min Kim ◽  
Robert Stewart ◽  
Sung-Wan Kim ◽  
Su-Jin Yang ◽  
Il-Seon Shin ◽  
...  

BackgroundCausal relationships between vascular factors and late-life depression are controversial.AimsTo investigate prospective associations between risk factors for vascular disease and incidence of late-life depression.MethodOf 661 community participants aged 65 years or over, without depression at baseline, 521 (79%) were re-evaluated 2 years later. At baseline and follow-up, a diagnostic interview for depression was carried out and information on vascular status, disability and cognitive function was gathered.ResultsPre-existing heart disease, incident stroke and lower baseline high-density lipoprotein cholesterol level were significantly associated with incidence of late-life depression, independently of disability and cognitive function.ConclusionsThese results provide some support for a vascular aetiology of late-life depression. However, important risk factors for cerebrovascular disease such as hypertension and diabetes were not implicated, and the associations with lipid levels might still be explained by affective states earlier in life.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Carlos Cantu-Brito ◽  
Erwin Chiquete ◽  
Jose L Ruiz-Sandoval ◽  
Fernando Flores-Silva

Background and Purpose: The objective of this study were to describe the proportion of patients eligible for the COMPASS trial among stable outpatients with either established atherothrombotic disease or major vascular risk factors, and to analyze 6-month incident stroke risk according vascular risk factors at baseline. Methods: We prospectively recruited 5,101 stable outpatients in 172 sites, within the Mexican INDAGA cohort study. Inclusion criteria were age >18 years and established atherothrombotic disease [history of either acute coronary syndromes (ACS), acute ischemic stroke (AIS)/transient ischemic attack (TIA) or peripheral artery disease (PAD)] or major vascular risk factors (age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors). Among these patients, we applied the selection criteria of the COMPASS trial for analysis, dividing the population in no COMPASS criteria met and COMPASS criteria met, and this last group subdivided among patients with previous AIS/TIA and without this antecedent, in order to stratify the risk for stroke during 6-month follow-up (incident AIS/TIA). Results: Among 5,101 stable outpatients with either established atherothrombotic disease (n=2,827) or major vascular risk factors (n=2,274), a total of 1,927 (37.8%) met COMPASS trial criteria: 1,054 (54.7%) with established cerebrovascular disease (past history of AIS/TIA) and 873 (45.3%) without. During 6-month follow-up, there were 89 incident AIS/TIA (39 AIS and 54 TIA): 1.7% among the whole population and 2.2% among the COMPASS subgroup. AIS/TIA occurred in a similar frequency among the COMPASS subgroup with established cerebrovascular disease (1.6%) and COMPASS without cerebrovascular disease (0.9%) (P=0.18). After a Cox-proportional hazards model, independent predictors of incident AIS/TIA were age ≥65 years (HR: 1.99, 95% CI: 1.29-3.07) and established cerebrovascular disease at baseline (HR: 1.61, 95% CI: 1.02-2.53). Conclusions: The majority of stable outpatients at vascular risk met COMPASS selection criteria and could be good candidates for low-dose rivaroxaban in addition to aspirin. Short-term predictors of AIS/TIA were old age and history of cerebrovascular disease


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Samantha Ferrari ◽  
Chiara Pagani ◽  
Mariella D'Adda ◽  
Nicola Bianchetti ◽  
Annamaria Pelizzari ◽  
...  

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=&lt;0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.


Author(s):  
J. Skov Neergaard ◽  
K. Dragsbæk ◽  
C. Christiansen ◽  
M. Asser Karsdal ◽  
S. Brix ◽  
...  

Background: Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer’s disease have failed. Objectives: The objective of this study was to identify subgroups of individuals with objective cognitive impairment (OCI), who were most likely to progress to dementia and to identify the risk factors associated with progression. Design: Prospective cohort study. Setting: Population-based. Participants: 5,380 elderly women from Denmark. Measurements: The Short Blessed Test and a category fluency test with animal naming, was used to assess cognitive function, and to classify them into different groups of OCI. Results: OCI was identified in 852 subjects at baseline. The risk of dementia was elevated for OCI subjects as compared to subjects with normal cognition (HR 1.46[1.19-1.79]). The courses of OCI were studied in a sub-cohort who completed the cognitive assessment at both the baseline and the follow-up visit (n = 1,933). Of these subjects 203 had OCI at baseline. The multi-domain subtypes of OCI were associated with progressive OCI. Subjects most likely to progress were older, physically inactive, had a higher level of total cholesterol (>6.5 mmol/L) and had a history of depression as compared to subjects with a non-progressive course of OCI. Conclusions: In this cohort we identified a risk profile associated with progression from OCI in older women. The degree of impairment at baseline was an important predictor of conversion to dementia, additionally several modifiable risk factors were associated with progression.


BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e026598 ◽  
Author(s):  
Andrea Benedetti ◽  
Yin Wu ◽  
Brooke Levis ◽  
Machelle Wilchesky ◽  
Jill Boruff ◽  
...  

IntroductionThe 30-item Geriatric Depression Scale (GDS-30) and the shorter GDS-15, GDS-5 and GDS-4 are recommended as depression screening tools for elderly individuals. Existing meta-analyses on the diagnostic accuracy of the GDS have not been able to conduct subgroup analyses, have included patients already identified as depressed who would not be screened in practice and have not accounted for possible bias due to selective reporting of results from only better-performing cut-offs in primary studies. Individual participant data meta-analysis (IPDMA), which involves a standard systematic review, then a synthesis of individual participant data, rather than summary results, could address these limitations. The objective of our IPDMA is to generate accuracy estimates to detect major depression for all possible cut-offs of each version of the GDS among studies using different reference standards, separately and among participant subgroups based on age, sex, dementia diagnosis and care settings. In addition, we will use a modelling approach to generate individual participant probabilities for major depression based on GDS scores (rather than a dichotomous cut-off) and participant characteristics (eg, sex, age, dementia status, care setting).Methods and analysisIndividual participant data comparing GDS scores to a major depression diagnosis based on a validated structured or semistructured diagnostic interview will be sought via a systematic review. Data sources will include Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO and Web of Science. Bivariate random-effects models will be used to estimate diagnostic accuracy parameters for each cut-off of the different versions of the GDS. Prespecified subgroup analyses will be conducted. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.Ethics and disseminationThe findings of this study will be of interest to stakeholders involved in research, clinical practice and policy.PROSPERO registration numberCRD42018104329.


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