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Table 2 Results of included studies

From: Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis

Study, year, study design Population Outcome measures (assessment methods) Confounder (measured) Results Risk of bias
Afzal et al., 2014 [1], prospective cohort study E1: 3715 E2: 4087 E3: 2384 Incidence of AD or dementia (ICD 8th and 10th edition diagnoses entered in the national Danish Patient Registry and the national Danish Causes of Death Registry) Gender, age, smoking status, BMI, leisure time and work-related physical activity, income level, education, diabetes mellitus, hypertension, alcohol consumption, cholesterol, creatinine, month of blood sample, seasonal adjusted vit D concentrations 418 subjects developed AD and 92 subjects vascular dementia, 14 subjects had both diagnoses. Risk of developing dementia: Analysis adjusted for all measured confounders: AD: E1 = reference, E2: HR = 1.23 (95% CI 0.97–1.55), E3: HR = 1.29 (95% CI 1.01–1.66) (p = 0.03) Vascular dementia: E1 = reference, E2(<50 nmol/L or 20 ng/mL): HR = 1.22 (95% CI 0.79–1.87), (p = 0.42) Combined: E1 = reference, E2: HR = 1.24 (95% CI 1.00–1.54), E3: HR = 1.27 (95% CI 1.01–1.60) (p = 0.02) unclear
Annweiler et al., 2011 [2], prospective cohort study E1: 33 (subtle cognitive impairment [2]) E2: 7 (subtle cognitive impairment [1]) Incidence of dementia (diagnosed by experts, according to DSM IV, NINCDS-ADRDA) Subtle cognitive impairment at baseline, presence of cardiovascular risk factors at baseline (age >85 years, hypertension, diabetes mellitus, BMI >25, lack of physical activity, smoking), diagnosis of Parkinson’s disease at baseline 10 women developed dementia, 4 of these AD E1: 3 E2: 7 (4 AD) Risk of developing Non-Alzheimer’s dementia Analysis adjusted for all measured confounders: E1 = reference E2: OR = 19.57 (95%CI 1.11–343.69) Risk of developing AD Unadjusted analysis: E1 = reference E2: OR = 1.06 (95%CI 0.97–1.15). high
Graf et al. 2014 [3], prospective cohort study E1: 15 (cognitively normal [11], MCI [4]) E2: 33 (cognitively normal [27], MCI [6] E2: 58 (cognitively normal [52]; MCI [6]) E3: 140 (cognitively normal [110, MCI [30]) Incidence of dementia (diagnosed by experts, validated cognitive scales, DSM IV-TR, NINCDS-ADRDA, ADDTC, and NINDS-AIREN) Gender, age, education level, basic (BADL) and instrumental (IADL) activities of daily living, comorbidities (CIRS), calcaemia, Vit B12 status, ApoE Eε4 genotype, mini nutritional assessment, albuminaemia, BMI 46 subjects developed dementia, 28 cognitively normal subjects and 18 with MCI. Analysis adjusted for all measured confounders: E1 = reference E2: RR = 2.87 (95% CI 0,36–22,77) E3: RR = 6.18 (95% CI 0,87–43,76) E4: RR = 2.85 (95% CI 0,45–17,95) Reclassification for Meta-Analysis: Analysis adjusted for all measured confounders: e1 = reference e2: RR = 4.55 (95% CI 1.04–19.82) e3: RR = 1.35 (95% CI 0.39–4.61) unclear
Knekt et al., 2014 [4], retrospective cohort study E1: 1240 E2: 1258 E3: 1216 E4: 1296 Incidence of dementia leading to hospitalisation (ICD 8 from the nationwide Finnish hospital discharge register or death certificates from Statistics Finland) Gender, age, month of blood sample, education level, marital status, leisure time physical activity, smoking status, BMI, alcohol consumption, hypertension, plasma fasting glucose concentration, serum triglyceride concentration, serum total cholesterol concentration 151 subjects developed dementia, 34 men and 117 women. E1: 21 (m = 13, f = 8) E2: 33 (m = 12, f = 21) E3: 37 (m = 5, f = 32) E4: 60 (m = 13, f = 47) Analysis adjusted for all measured confounders: Men: E1: HR = 0.74 (95% CI 0.29–1.88) E2: HR = 0.63 (95% CI 0.25–1.56), E3: HR = 0.41 (95% CI 0.14–1.19), E4 = reference Women: E1: HR = 0.33 (95% CI 0.15–0.73) E2: HR = 0.60 (95% CI 0.34–1.06), E3: HR = 0.90 (95% CI 0.56–1.44), E4 = reference Combined: E1: HR = 0.48 (95% CI 0.28–0.84) E2: HR = 0.62 (95% CI 0.39-1.00), E3: HR = 0.75 (95% CI 0.49-1.14), E4 = reference unclear
Littlejohns et al., 2014 [5], prospective cohort study E1: 1169 E2: 419 E3: 70 Incidence of dementia (diagnosed by experts, annual cognitive assessments, NINCDS-ADRDA) Age, season of vit D collection, education, gender, BMI, smoking, alcohol consumption, depressive symptoms, diabetes, hypertension, ethnicity, income, occupation 171 subjects developed dementia, 102 of these AD E1: n.s. E2: n.s. E3: n.s. Analysis adjusted for age, season of vit D collection, education, gender, BMI, smoking, alcohol consumption, depressive symptoms: Dementia: E1 = reference, E2: HR = 1.53 (95% CI 1.06–2.21), E3: HR = 2.25 (95% CI 1.23–4.13) (p = 0.002) AD: E1 = reference, E2: HR = 1.69 (95% CI 1.06–2.69), E3: HR = 2.22 (95% CI 1.02–4.83) (p = 0.008) Similar results for analysis that additionally adjusted for diabetes and hypertension (data not shown). unclear
Schneider et al. 2014 [6], prospective cohort study E1: Whites 285; Blacks 267 E2: Whites 283; Blacks 272 E3: Whites 284; Blacks 261 Incidence of AD or dementia leading to first hospitalisation (ICD 9 from hospital discharge records) Gender, age, education, income, smoking, alcohol consumption, physical activity, BMI, waist circumference, use of vit D supplements, diabetes, hypertension, use of hypertension medication, cholesterol, estimated glomerular filtration rate, calcium status, phosphate, PTH, season adjusted vit D concentrations 145 subjects developed AD or dementia. E1: Whites 18; Blacks 23 E2: Whites 31; Blacks 24 E3: Whites 24; Blacks 25 Analysis adjusted for age, gender, education, income, physical activity, smoking, alcohol consumption, BMI, wait circumference, use of vit D supplements: Whites: E1 = reference, E2: HR = 1.74 (95% CI 0.95–3.18), E3: HR = 1.32 (95% CI 0.69–2.55) Blacks: E1 = reference, E2: HR = 1.22 (95% CI 0.68–2.19), E3: HR = 1.53 (95% CI 0.84–2.79) Reclassification for Meta-Analysis: 145 subjects developed AD or dementia. e1: 75 out of 876 e2: 63 out of 694 e3: 7 out of 82 Analysis adjusted for age, gender, education, income, physical activity, smoking, alcohol consumption, BMI, waist circumference, use of vit D supplements: e1 = reference e2: HR = 1.22 (95% CI 0.85-1.74) e3: HR = 1.44 (95% CI 0.65-3.21) unclear
  1. Abbreviations: AD Alzheimer’s diseases, APOE ε4 apolipoproteine E ε4 genotype, ADDTC Alzheimer’s Disease Diagnostic and Treatment Centres, BMI Body-Mass Index, BADL Basic Activities of Daily Living, CIRS Cumulative Index Rating Scale, DSM-IV-(TR) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (Text Revision), E or e exposure, f female, HR hazard ratio, IADL Instrumental Activities of Daily Living, ICD International Classification of Diseases, y years, n.s. not specified, CI confidence interval, m male, n number, NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association, NINDS-AIREN National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l’Enseignement en Neurosciences, ADDTC Alzheimer’s Disease Diagnostic and Treatment Centers, p p-value, PTH parathormone, RR relative risk, SD standard deviation, vit D vitamin D, vit B12 vitamin B12, OR odds ratio, MCI mild cognitive impairment