Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year Follow-up Study.
TL;DR: Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia and analysis of depressive trajectories over 28 years suggests that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes.
Abstract: Importance Neuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate Objective To characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia Design, Setting, and Participants Up to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015 Data analysis for this study in a UK general community was conducted from October to December 2016 Exposures Depressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire Main Outcomes and Measures Incidence of dementia (n = 322) between 1985 and 2015 Results Of the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%) Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 121; 95% CI, 095-154) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions However, those with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 172; 95% CI, 121-244) Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk (HR, 102; 95% CI, 072-144) but those with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 167; 95% CI, 111-249) Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared with those without dementia became apparent 11 years (difference, 061; 95% CI, 009-113; P = 02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 581; 95% CI, 481-681; P Conclusions and Relevance Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes The findings do not support the hypothesis that depressive symptoms increase the risk for dementia
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University College London1, Camden and Islington NHS Foundation Trust2, King's College London3, University of Melbourne4, University of Exeter5, Brighton and Sussex Medical School6, University of Manchester7, Tel Aviv University8, Johns Hopkins University9, University of Michigan10, University of Washington11, Kaiser Permanente12, University of Montpellier13, University of Edinburgh14, Dalhousie University15, University of Southern California16, University of Oslo17, Innlandet Hospital Trust18
TL;DR: The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what the authors should do to prevent and manage dementia.
3,826 citations
Camden and Islington NHS Foundation Trust1, University College London2, Royal Melbourne Hospital3, University of Exeter4, University of Plymouth5, University of Cambridge6, University of Manchester7, Tel Aviv University8, Goa Medical College9, Johns Hopkins University10, University of California, Davis11, Kaiser Permanente12, University College Hospital, Ibadan13, University of Montpellier14, Dalhousie University15, University of Southern California16, Oslo University Hospital17, University of Washington18
TL;DR: Author(s): Livingston, Gill; Huntley, Jonathan; Sommerlad, Andrew ; Sommer Glad, Andrew; Ames, David; Ballard, Clive; Banerjee, Sube; Brayne, Carol; Burns, Alistair; Cohen-Mansfield, Jiska; Cooper, Claudia; Costafreda, Sergi G; Dias, Amit; Fox, Nick; Gitlin, Laura N; Howard, Robert; Kales, Helen C;
3,559 citations
TL;DR: There were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotic drugs, bladder antimuscarinics, and antiepileptic drugs after adjusting for confounding variables.
Abstract: Importance Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia. Objective To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older. Design, Setting, and Participants This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018. Exposures The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date). Main Outcomes and Measures Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables. Results Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%. Conclusions and Relevance Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.
318 citations
TL;DR: A robust association between some classes of anticholinergic drugs and future dementia incidence was observed, and this could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia.
Abstract: Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. Design Case-control study. Setting General practices in the UK contributing to the Clinical Practice Research Datalink. Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. Interventions Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia. Main outcome measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis. Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure. Trial registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
295 citations
References
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TL;DR: The CES-D scale as discussed by the authors is a short self-report scale designed to measure depressive symptomatology in the general population, which has been used in household interview surveys and in psychiatric settings.
Abstract: The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.
48,339 citations
TL;DR: There was an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis, and self-perceived health status and symptoms were worse in subjects in lower status jobs.
3,492 citations
"Trajectories of Depressive Symptoms..." refers background or methods in this paper
...Covariates (1985, 1991, 1997, and 2003) Sociodemographic factors included age, sex, race/ethnicity (white and nonwhite), marital status (married/cohabiting vs other), education (no formal education, lower secondary school, higher secondary school, university, or higher degree), and occupational position, a 3-level variable related to salary, social status, and level of responsibility at work.(12) Health behaviors included smoking (current, former, and never smoker), alcohol consumption (categorized as no/ occasional,moderate [1-21 alcohol units perweek formenand 14 alcohol units per week for women], and heavy [≥21 units per week for men and 14 units per week for women]), physical activity (hours per week ofmoderate or vigorous physical activity), and frequency of fruit and vegetable consumption (less than once daily, once daily, or more than once daily)....
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...Study Design and Participants TheWhitehall II study isanongoingcohort studyof 10308persons (6895menand3413women), aged35 to 55years at study recruitment in 1985.(12) Participants responded to a questionnaire andunderwent a structured clinical evaluation, consisting of measures of anthropometry and cardiovascular and metabolic risk factors anddiseases....
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TL;DR: In this article, a model of the major biomarkers of Alzheimer's disease (AD) was proposed and the authors described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms.
Abstract: Summary In 2010, we put forward a hypothetical model of the major biomarkers of Alzheimer's disease (AD). The model was received with interest because we described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms. Since then, evidence has accumulated that supports the major assumptions of this model. Evidence has also appeared that challenges some of our assumptions, which has allowed us to modify our original model. Refinements to our model include indexing of individuals by time rather than clinical symptom severity; incorporation of interindividual variability in cognitive impairment associated with progression of AD pathophysiology; modifications of the specific temporal ordering of some biomarkers; and recognition that the two major proteinopathies underlying AD biomarker changes, amyloid β (Aβ) and tau, might be initiated independently in sporadic AD, in which we hypothesise that an incident Aβ pathophysiology can accelerate antecedent limbic and brainstem tauopathy.
3,197 citations