Table 3

Results for 22 studies included in systematic review

Study	Result		Covariates adjusted for	Risk factor handling
Betula Study99	1: Health factors at baseline predicted cognitive change between waves 1 and 3 Metabolic component predicted fall in performance on recall, recognition, spatial ability and phonemic fluency (P<0.001 for all). Glycaemic component predicted fall in performance on recall (P<0.001), recognition (P<0.01), spatial ability (P<0.01), phonemic fluency (P<0.001). Lipid component predicted fall in performance on recall (P<0.001), recognition (P<0.01), spatial ability (P<0.001), phonemic fluency (P<0.001). Thyroid component predicted fall in performance on recall (P<0.05), recognition (P<0.01). Inflammatory component predicted rise in performance on recall (P<0.001), spatial ability (P<0.001), phonemic fluency (P<0.01). Nutritional component predicted rise in performance on recognition (P<0.01), phonemic fluency (P<0.01). There was no relationship between any health component and semantic fluency. 2: Change in health factors between waves 1 and 2 associated with cognitive change between waves 1 and 2. Glycaemic change predicted fall in performance on recognition (P<0.05), phonemic fluency (P<0.05). Lipid change predicted fall in spatial ability (P<0.01). Inflammatory change predicted rise in performance on recall (P<0.001), recognition (P<0.01), spatial ability (P<0.001). 3: Change in health factors between waves 1 and 2 predicting cognitive change between waves 2 and 3. Glycaemic change predicted fall in performance on recall (P<0.05), recognition (P<0.01). Numerical results from each model are too numerous to include here.99		Not stated.	Clustering: principal components analysis.
Cache County Study95	Four lifestyle classes identified: Unhealthy religious (11.5%) Unhealthy non-religious (10.5%) Healthy moderately religious (38.5%) Healthy very religious (39.5%). Compared with unhealthy religious: for dementia: unhealthy non-religious HR 0.54 (95% CI 0.31 to 0.93). Healthy moderately religious HR 0.56 (95% CI 0.38 to 0.84). Healthy very religious HR 0.58 (95% CI 0.40 to 0.84). Difference between the three classes above is non-significant. Reported as similar for Alzheimer’s disease (AD).		Age, sex, education, recruitment cohort and apolipoprotein (APOE) ε4 status.	Clustering: latent class analysis to identify clusters.
Cardiovascular Risk Factors, Ageing and Dementia study101	20% had no baseline risk factors 41% had 1, 32% had 2, 7% had 3 baseline risk factors. Compared with those with no baseline risk factors: for dementia: one risk factor OR 1.37 (95% CI 0.44:4.27) two risk factors OR 3.03 (95% CI 1.03:8.89) three risk factors OR 6.21 (95% CI 1.94:19.92) n=1409 in the model. Relationship reported to be similar for AD.		Age, sex, education and follow-up time.	Unweighted risk factor score.
Coronary Artery Risk Development in Young Adults90	Prevalence of meeting the ideal metric (see definition in previous column) decreased over the 25 year follow-up for all factors except non-smoking. Higher scores of ideal health components at year 0 and the average across years 0, 7, 25 was associated with better performance on all three tests. Trend tests for cognitive performance and increasing score show significant results for all three cognitive tests for health component score at baseline and the average across the study. Each additional ideal health component (average exposure) was associated with 1.32 more symbols on the Digit Symbol Substitution Test (95% CI 0.93 to 1.71), a 0.77 point lower interference score on the Stroop test (95% CI −1.03 to 0.45) and 0.12 more words recalled on the Rey Auditory Verbal Learning Test (95% CI 0.04 to 0.20). Similar patterns were shown when the score cut point of ≥5 was used, that is, greater ideal health associated with better cognitive performance. Using the 0–14 score also resulted in a similar pattern of results. Sensitivity analysis using only those with complete data found similar results.		Age, sex, race (black/white), education, alcohol use and study centre.	Unweighted risk factor score.
Framingham Study96	Limited information provided in the article. Results for the scoring are provided in figure 1 of the article. The figure shows the highest cognitive scores in those with neither risk factor at baseline, the lowest scores in those with both risk factors and an intermediate level for those with one risk factor. Results showed that a score of 1 or 2 was worse than a score of 0 for visual reproduction (P<0.002) and that a score of 2 was worse than a score of 0 or 1 for logical memory delayed recall (P<0.03).		Not stated	Unweighted risk factor score.
Honolulu Asia Ageing Study88	Risk factor scores >1 SD above the mean were considered to be elevated; 24% had no elevated risk factors, 29% had 1 and 30% had 2 or more. Per one unit increase in summed z score adjusted for age and education, for dementia relative risk (RR) 1.06 (95% CI 1.02 to 1.10), AD RR 1.00 (95% 0.94 to 1.06), vascular dementia (VaD) RR 1.11 (1.04 to 1.18). Compared with those with no elevated risk factors, for dementia 1 risk factor RR 0.9 (95% CI 0.62 to 1.32). ≥2 risk factors RR 1.56 (95% CI 1.12 to 2.18). Results were stronger for VaD.		Age and education	Unweighted risk factor score.
Hoorn Study102	OR per point increase in risk factor score when only modifiable risk factors are included. Information processing speed OR 1.22 (95% CI 0.99 to 1.51). Attention and executive function OR 1.26 (95% CI 1.04 to 1.54). Visuoconstruction OR 1.26 (95% CI 0.94 to 1.69). Abstract reasoning OR 1.25 (95% CI 0.91 to 1.71). Language OR 1.09 (95% CI 0.79 to 1.51). Memory OR 0.84 (95% CI 0.68 to 1.03).		Z scores were adjusted on an individual basis for age, sex, IQ.	Weighted risk factor score, modifiable risk factor score was unweighted.
Intervention project on cerebrovascular disease and dementia in the district of Ebersberg104	For total score: Score 9–12 HR 1 reference Score 5–8 HR 0.98 (95% CI 0.72 to 1.33) Score 0–4 HR 1.41 (95% CI 0.91 to 2.20) For blood parameters alone: Score 4–6 HR 1 reference Score 3 HR 0.79 (95% CI 0.60 to 1.05) Score 0–2 HR 0.95 (95% CI 0.72 to 1.25) For health behaviours alone: Score 4–6 HR 1 reference Score 3 HR 0.98 (95% CI 0.73 to 1.31) Score 0–2 HR 1.41 (95% CI 1.28 to 1.80)		Age, sex, education.	Unweighted risk factor score.
Kaiser Permanente Medical Care Program93	Cardiovascular composite score for risk of dementia: 1 risk factor HR 1.27 (95% CI 1.02 to 1.58) 2 risk factors HR 1.59 (95% CI 1.28 to 1.98) 3 risk factors HR 2.19 (95% CI 1.63 to 2.93) 4 risk factors HR 2.61 (95% CI 1.22 to 5.60)		Age at midlife, age at case ascertainment, race, education, sex.	Unweighted risk factor score.
Kungsholmen project100	In over 6406 participant years of follow-up, there were 428 cases of dementia including 328 of AD. Overall, higher risk scores were associated with greater risk of incident dementia and AD. Overall vascular risk profile score Dementia 0 Reference category 1 hour 1.11 (95% CI 0.79 to 1.58) 2 hours 1.65 (95% CI 1.12 to 2.42) ≥3 hours 2.48 (95% CI 1.46 to 4.20), p for trend <0.001 AD 0 reference category 1 hour 1.09 (95% CI 0.75 to 1.60) 2 hours 1.77 (95% CI 1.16 to 2.71) ≥3 hours 2.66 (95% CI 1.39 to 5.08), p for trend <0.001. Similar patterns, atherosclerotic risk profile, hypoperfusion risk profile.		Age, sex, education, baseline Mini-Mental State Examination (MMSE), BMI, antihypertensive use, coronary heart disease, APOE ε4 and survival status at follow-up.	Unweighted risk factor score.
Maastricht Ageing Study103	Risk score and incident dementia HR 1.19 (95% CI 1.08 to 1.32). Risk score and incident cognitive decline HR 1.09 (95% CI 1.004 to 1.18). No association for linear mixed models. Per point increase in risk score.		Age, sex and education.	Weighted risk factor score.
Northern Manhattan Study91	Analysis excluding those with cognitive impairment at baseline. For change in Executive function 2 vs 0–1 ideal health factors beta 0.076 (SE 0.116), p=0.513. 3 vs 0–1 ideal health factors beta 0.325 (SE 0.118), p=0.006. 4–7 vs 0–1 ideal health factors beta 0.091 (SE 0.133), p=0.497. Semantic memory 2 vs 0–1 ideal health factors beta 0.220 (SE 0.111), p=0.047. 3 vs 0–1 ideal health factors beta 0.224 (SE 0.112), p=0.047. 4–7 vs 0–1 ideal health factors beta 0.222 (SE 0.128), p=0.082. Episodic memory 2 vs 0–1 ideal health factors beta 0.268 (SE 0.115), p=0.020. 3 vs 0–1 ideal health factors beta 0.321 (SE 0.117), p=0.006. 4–7 vs 0–1 ideal health factors beta 0.314 (SE 0.132), p=0.018. Processing speed 2 vs 0–1 ideal health factors beta 0.343 (SE 0.115), p=0.003. 3 vs 0–1 ideal health factors beta 0.392 (SE 0.117), p=0.001. 4–7 vs 0–1 ideal health factors beta 0.489 (SE 0.133), p<0.001.		Sex, race, medical insurance, time from baseline to neuropsychological data collection wave 1.	Unweighted risk factor score.
Personality and Total Health, Path through life study108	Overall higher PATHrisk score was associated with poorer cognitive function on all cognitive tests except reaction time. For relationships between PATHrisk and change in cognitive measures over time: the model including gender, time, PATHrisktime and PATHrisk: found an association between PATHrisktime and choice reaction time (beta −0.024 (SE 0.01)) The model including gender, time, education, timePATHrisk and educationPATHrisk found no association between PATHrisk*time and cognitive score change. No relationship for individual risk factors. No relationship with global cognitive score.		Patterns of test completion.	Unweighted risk factor score.
San Luis Valley Health ad Aging Study92	The Hispanic population had a worse risk factor profile than the white population. General cognitive decline (MMSE) any 1 risk factor OR 1.09 (95% CI 0.70 to 1.71), any 2 risk factors OR 1.10 (95% CI 0.69 to 1.73), all 3 risk factors OR 1.15 (95% CI 0.63 to 2.12). Executive function decline (Behavioural Dyscontrol Scale) any 1 risk factor OR 1.07 (95% CI 0.59 to 1.92), any 2 risk factors OR 1.16 (95% CI 0.64 to 2.11), all 3 risk factors OR 1.45 (95% CI 0.69 to 3.07).		Decade of age and education. Comparator not clear: assumed to be no risk factors.	Unweighted risk factor score.
Supplementation en vitamines et mineraux antioxydants study105	In the final model, adjusting for other lifestyle risk factors plus those in next column, the only statistically significant relationship remaining was for alcohol comparing abstainers to users −1.26 (95% CI –2.11 to −0.40) such that abstainers had poorer verbal memory outcomes. For score of unhealthy behaviours: Compared with 0–1 unhealthy behaviours: for global composite cognitive performance at follow-up. 2 unhealthy behaviours mean difference in cognitive performance −1.57 (95% CI −2.98 to −0.16). 3 unhealthy behaviours mean difference in cognitive performance −1.69 (95% CI −3.06 to −0.33). 4 unhealthy behaviours mean difference in cognitive performance −1.75 (95% CI −3.20 to −0.30). 5–6 unhealthy behaviours mean difference in cognitive performance −2.10 (95% CI −3.82 to −0.37). Similar patterns for score used as a continuous variable and for the same analyses with executive function and verbal memory outcomes. When looking at latent lifestyle factors, low fruit and vegetable consumption and low physical activity level appeared to be the main contributors to the unhealthy behaviours related to verbal memory. The unhealthy lifestyle latent factor was not associated with executive function.		Age, sex, education, time-lag baseline to cognitive evaluation, occupational status, trial intervention group, energy intake, number of 24 hours records, BMI, depressive symptoms, baseline self-reported memory troubles, history of diabetes, hypertension and cardiovascular diseases.	Clustering: latent factors/unweighted scoring.
Suwon Longitudinal Ageing Study109	Greater number of positive factors (non-smoking, vegetable consumption, physical activity and social activity) associated with greater change on MMSE. Implied that change is associated with positive cognitive outcome. 1 protective factor beta 0.441 (SE 0.348). 2 protective factors beta 1.353 (SE 0.348). 3 protective factors beta 1.731 (SE 0.362). When all factors entered into the same model only vegetable consumption and social activity remained statistically significant. Non-smoking beta 0.393 (SE 0.253). Physical activity beta 0.310 (SE 0.195). Vegetable consumption beta 0.698 (SE 0.176). Social activity beta 0.626 (SE 0.187). No obvious pattern in particular combinations of protective factors. These analyses include the whole data set without exclusion of those with prevalent cognitive impairment. The authors report that they carried out sensitivity analyses excluding those with MMSE scores<19 and that the magnitude of the association diminished, although the direction of the association did not change.		Age, sex, marital status, education, lifetime occupation, diabetes, heart disease, hypertension and stroke.	Unweighted risk factor score.
Uppsala Longitudinal Study of Adult Men98	Risk factors at age 50, reference none AD: 1: HR 0.9 (95% CI 0.6 to 1.5); 2: HR 1.2 (95% CI 0.8 to 2.0); ≥3: HR 0.5 (95% CI 0.2 to 1.2). Vascular dementia: 1: HR 2.1 (95% CI 0.9 to 4.6); 2: HR 2.8 (95% CI 1.3 to 6.2); ≥3: HR 5.1 (95% CI 2.2 to 11.9). AD, mixed or unspecified dementia: 1: HR 1.3 (95% CI 0.9 to 1.9); 2: HR 1.5 (95% CI 1.0 to 2.2); ≥3: HR 1.4 (95% CI 0.9 to 1.4) All dementia: 1: HR 1.4 (95% CI 1.0 to 1.9); 2: HR 1.7 (95% CI 1.2 to 2.3); ≥3: HR 2.1 (95% CI 1.5 to 3.2).	Risk factors at age 70 years—reference none AD: 1: HR 1.0 (95% CI 0.8 to 2.3); 2: HR 2:1.0 (95% CI 0.6 to 1.9); ≥3: HR 0.4 (95% CI 0.1 to 1.3). Vascular dementia: 1: HR 4.1 (95% CI 1.0 to 17.7); 2: HR 6.8 (95% CI 1.6 to 29.2); ≥3: HR 7.7 (95% CI 1.6 to 37.1). AD, mixed or unspecified dementia: 1: HR 1.6 (95% CI 1.1 to 2.5); 2: HR 1.4 (0.9 to 2.2); ≥3: HR 1.1 (0.5 to 2.1) All dementia: 1: HR 1.8 (95% CI 1.2 to 2.6); 2: HR 1.7 (95% CI 1.1 to 2.6); ≥3: HR 1.7 (95% CI 1.0 to 2.9).	Age and education.	Unweighted risk factor score.
Washington Heights cohort89	For probable and possible AD combined, diabetes, hypertension, heart disease and smoking were retained in multivariable analyses; 26.0% had no risk factors, 37.8% had 1 risk factor, 25.3% had 2 risk factors, 9.4% had 3 risk factors and 0.9% had all risk factors. When all four risk factors were included in the same model only diabetes (HR 2.0 (95% CI 1.4 to 2.9) and current smoking (HR 1.9 (95% CI 1.4 to 2.9) retained statistical significance. The corresponding results for heart disease and hypertension were HR 1.1 (95% CI 0.8 to 1.5) and HR 1.1 (95% CI 0.9 to 1.5). When number of risk factors was examined: Compared with no risk factors for probable or possible AD: 1 risk factor HR 1.6 (95% CI 1.1 to 2.4); 2 risk factors HR 2.6 (95% CI 1.7 to 3.8); 3 or 4 risk factors HR 3.8 (95% CI 2.4 to 5.9).		Age and sex, a subsample additionally adjusted for education and APOE ε4 showed similar results.	Unweighted risk factor score.
Washington Heights cohort97	Combined diet and physical activity. For the sample excluding those with a baseline clinical dementia rating scale score of 0.5 and with <2 years follow-up. Low activity, low diet AD HR 1.00 reference; Low activity, high diet HR 0.70 (95% CI 0.50 to 1.28); High activity, low diet score HR 0.61 (95% CI 0.38 to 0.97); High activity, high diet score HR 0.51 (95% CI 0.31 to 0.83); Patterns of results were similar for the whole sample.		Cohort, age, sex, ethnicity, education, APOE ε4 status, caloric intake, BMI, smoking, depression, leisure activities, comorbidity index, time between first dietary and first physical activity assessment.	Weighted risk factor score.
Washington Heights cohort94	No real impact of vascular burden on cognitive change, risk factors were associated with a small attenuated decline in memory on black but not white or Hispanic participants. For annual change in general cognitive performance; white −0.03 (95% CI −0.13 to 0.07), black 0.10 (95% CI 0.02 to 0.18), Hispanic 0.06 (95% CI −0.02 to 0.14); For annual change in executive function; white −0.03 (95% CI −0.13 to 0.07), black 0.02 (95% CI −0.06 to 0.10), Hispanic 0.0 (95% CI −0.06 to 0.10); For annual change in memory; white 0.00 (95% CI −0.10 to 0.10), black 0.11 (95% CI 0.05 to 0.17), Hispanic 0.06 (95% CI 0.00 to 0.12).		Age, sex, education, recruitment cohort and APOE ε4 status.	Unweighted risk factor score.
Whitehall II study106	Slopes from growth curve models estimating the combined effect of alcohol and smoking at baseline (1997–1999) on cognitive decline (2002–2004 to 2007–2009). Being a heavy drinker and current smoker was associated with faster decline. Non-drinker and: Never smoker −0.40 (95% CI −0.46 to −0.34); Ex-smoker −0.38 (95% CI −0.46 to −0.30); Current smoker −0.50 (95% CI −0.65 to −0.35). Moderate drinker (within UK recommended limits) and: Never smoker −0.42 (95% CI −0.45 to −0.39); Ex-smoker −0.42 (95% CI −0.45 to −0.38); Current smoker −0.37 (95% CI −0.44 to −0.29). Heavy drinker (>UK recommended limits) and: Never smoker −0.42 (95% CI −0.47 to −0.37); Ex-smoker −0.45 (95% CI −0.49 to −0.41); Current smoker −0.57 (95% CI −0.67 to −0.48). Sensitivity analysis to exclude those with MMSE<24 at follow-up showed similar results.		Age, gender, prevalent chronic disease and education	Used categories to examine additive impact.
Whitehall II study107	At baseline: 8.4% had no unhealthy behaviours. Other data not given. Examining the relationship between unhealthy behaviours at phase I and poor executive function at phase VII: Compared with no unhealthy behaviours: Those with: 1 unhealthy behaviour OR 1.34 (95% CI 0.96 to 1.87); 2 unhealthy behaviours OR 1.38 (95% CI 0.99 to 1.93); 3–4 unhealthy behaviours OR 1.84 (95% CI 1.27 to 2.65). Examining the relationship between unhealthy behaviours at phase I and poor executive function at phase V: compared with no unhealthy behaviours: Those with: 1 unhealthy behaviour OR 1.38 (95% CI 1.09 to 1.74); 2 unhealthy behaviours OR 1.83 (95% CI 1.43 to 2.33); 3–4 unhealthy behaviours OR 2.38 (95% CI 1.76 to 3.22). Similar pattern for unhealthy behaviour at phase I and memory. No clear patterns for different combinations of health behaviours. Cumulative score of summed health behaviours over time. Compared with those scoring 0–2: for executive function: 3–5 OR 1.58 (95% CI 1.27 to 1.98); 6–8 OR 2.52 (95% CI 1.96 to 3.24); 9–12 OR 2.87 (95% CI 1.90 to 4.32). Similar pattern for memory.		Age, sex and socioeconomic position at the corresponding stage of assessment.	Unweighted risk factor score.