Study Title and Description
The association between caffeine and cognitive decline: examining alternative causal hypotheses.
Key Questions Addressed
|1||For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on behavior*?|
Primary Publication Information
|Title||The association between caffeine and cognitive decline: examining alternative causal hypotheses.|
|Author||K Ritchie,ML Ancelin,H Amieva,O Rouaud,I Carrière,|
Secondary Publication Information
There are currently no secondary publications defined for this study.
Extraction Form: Behavior - Design Details - INCLUDED Studies
No arms have been defined in this extraction form.
|Question... Follow Up||Answer||Follow-up Answer|
|What outcome is being evaluated in this paper?||Behavior|
|What is the objective of the study (as reported by the authors)?||In the present study, data from a large prospective general population study with information on caffeine consumption, type 2 diabetes, fasting glucose levels, plasma Aβ levels, cognitive functioning and AD diagnosis, as well as data on a wide range of potential clinical and life-style confounders are used in order to examine alternative pathways linking caffeine and cognitive performance.|
|Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods)||Study population Subjects were recruited as part of a multi-site cohort study of community-dwelling persons aged 65 years and over from the electoral rolls of three French cities (Bordeaux, Dijon, and Montpellier) between 1999 and 2001 (the Three City Study). Between January 1999 and March 2001 9,294 persons were recruited, of whom 214 were eliminated due to a dementia diagnosis at baseline and 825 had missing data on one of the covariates. A sub-set of 1,193 persons had data on concentrations of serum Aβ. Subjects were examined at baseline and two, four, and seven years follow-up. The flow chart showing the numbers of participants included in the analyses is presented in Figure 2. Participants with missing data for the covariates or for caffeine were excluded (Figure 2, n = 825); they were older (p < 0.0001), had a lower educational level (p < 0.0001), and were also more likely to have vascular disease (<0.0001), hypertension (p = 0.0002), and mobility restriction (p < 0.0001). The study design and detailed methodology has been described elsewhere (The 3C Study Group, 2003). The study protocol was approved by the Ethical Committee of the Bicêtre University- Hospital (France) and written informed consent was obtained from each participant. Caffeine consumption Questions relating to caffeine consumption were part of a standardized interview administered by either psychologists or research nurses at baseline and two and four years. Number of cups normally consumed per day of tea and coffee were noted. Other forms of caffeine (e.g. colas, cocoa) were consumed too rarely by this elderly cohort to warrant inclusion, as already reported (Ritchie et al., 2007). Calculations were made on the assumption of one cup of coffee containing 100 mg of caffeine and tea 50 mg, the total average consumption per day being calculated per subject in caffeine units (one unit = 100mg). High caffeine consumers defined as taking three units or more. Depressive symptomatology was assessed at baseline and during the follow-up by the Center for Epidemiological Studies-Depression scale (CESD) (Radloff, 1977) with a 16 cut-off point or a diagnosis of current major depressive episode according to DSM-IV by the Mini-International Neuropsychiatry Interview (MINI) (Lecrubier, 1997). Information on depressive symptomatology was not available for Dijon at seven-year follow-up. Cross-sectional associations of caffeine consumption with diabetes or depressive symptoms were assessed using logistic regression models and stratifying by gender due to previous findings of gender specific associations of caffeine consumption with cognitive decline (Ritchie et al., 2007). A Cox model with delayed entry and taking age as the basic time scale and birth as the time origin was used in the longitudinal analysis of the incidence of diabetes or depressive symptoms over the seven-year followup in participants free of baseline diabetes or depressive symptoms respectively (Figure 2). In order to establish whether diabetes and depression could be considered intermediate variables in the relationship between caffeine consumption and cognitive performance, we adopted the three-phase definition of mediation proposed by Kraemer et al. (2001) namely that (i) caffeine consumption precedes the mediator and a longitudinal relationship is established between them, (ii) the mediator is related to the incidence of cognitive decline, and (iii) when caffeine consumption and the mediator (Me) are jointly entered in a model explaining cognitive decline incidence either Me "dominates" caffeine consumption (total mediation) or caffeine consumption and Me codominate (partial mediation).|
|How many outcome-specific endpoints are evaluated?||1|
|What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately)||depression|
|List additional health endpoints (separately).|
|List additional health endpoints (separately)|
|What is the study design?||Cross-sectional|
|Randomized or Non-Randomized?|
|What were the diagnostics or methods used to measure the outcome?||Subjective|
|Optional: Name of Method or short description||Depressive symptomatology was assessed at baseline and during the follow-up by the Center for Epidemiological Studies-Depression scale (CESD) (Radloff, 1977) with a 16 cut-off point or a diagnosis of current major depressive episode according to DSM-IV by the Mini-International Neuropsychiatry Interview (MINI) (Lecrubier, 1997).|
|What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.)||<3 cups of caffeine vs ≥ 3 cups of caffeine; 1 cup of caffeine = 100 mg|
|What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models. Copy from methods)||Univariate models (Model 0) were adjusted only for age and center while multivariable models (Model 1) further adjusted for covariates found to be significant at p < 0.10 in cross-sectional or longitudinal analyses; education level, cardiovascular pathologies, hypertension, BMI, HDL cholesterol, triglycerides and mobility (for diabetes only), and respiratory pathologies (for depression only).|
|Provide a general description of results (as reported by the authors).||In both men and women the fully adjusted model showed no significant relationship between caffeine consumption at baseline and either prevalent or incident depressive symptoms, although a non-significant trend was observed for lower depression in women only. Given the weak longitudinal association between high caffeine consumption and both diabetes (a protective effect with p-value = 0.03 in men and an at-risk effect with p-value = 0.02 in women) and depressive symptoms (non-significant protective effect with p = 0.19 in men and p = 0.07 in women) the first step in the establishment of mediation could not be established so a full model to explain cognitive decline was not constructed. cross-sectional: no effect in women (OR= 0.92 95% CI 0.80- 1.06) or men (OR= 0.94, 95% CI 0.76- 1.18) Longitudinal: no effect in women (OR= 0.86 95% CI 0.74- 1.01) or men (OR= 0.85, 95% CI 0.66- 1.08)|
|Did the authors perform a dose-response analysis (or trend/related analysis)?||Yes|
|What were the authors's observations re: trend analysis?||In both men and women the fully adjusted model showed no significant relationship between caffeine consumption at baseline and either prevalent or incident depressive symptoms, although a non-significant trend was observed for lower depression in women only.|
|What were the author's conclusions?||This study showed that high coffee consumption did not reduce the incidence of depression over seven-year follow-up in although there was a nonsignificant trend for women. This finding is contrary to those of previous prospective studies which did not, however, adequately adjust for cardiovascular pathologies.|
|What were the sources of funding?||The 3C Study is conducted under a partnership agreement between Inserm, the Victor Segalen – Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and first phase of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, the Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Regional Governments of Aquitaine, Bourgogne and Languedoc-Roussillon and, the Fondation de France, the Ministry of Research-Inserm Programme "Cohorts and collection of biological material."|
|What conflicts of interest were reported?||Karen Ritchie has received travel costs for attending the annual scientific meeting of the International Coffee Manufacturers Association.|
|Does the exposure (dose) need to be standardized to the SR?||No|
|Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).|
|List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot. Characterize value as LOAEL/NOAEL, etc. if possible.||depression - NOAEL = ≥ 300 mg caffeine/day|
|Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot.||no effect at levels below Nawrot. caffeine consumption may be protective|
|What is the importance of the study with respect to the adverseness of the outcome?||Important|
No baseline characteristics have been defined for this extraction form.
Results & Comparisons
No Results found.
|Arm or Total||Title||Description||Comments|
No quality dimensions were specified.
No quality rating data was found.