Background
Methods
Literature search
Inclusion criteria
Study selection
Data extraction
Study quality
Data synthesis
Ratings of quality of evidence
Results
Study characteristics
Reference, study design, study name (period) | Location, setting, funding | Population, baseline characteristics | Exposure (measurement), collection period | Follow-up period | Risk of bias |
---|---|---|---|---|---|
Afzal et al., 2014 [1], prospective cohort study, Copenhagen City Heart Study (1981–1983) | Denmark, general population (population register), public research funding and material sponsorship from Diarosin Liasion | 10,186 individuals without dementia Women % (n): 56.1% (5718) Age in y (median, range): total: n.s.; E1: 57 (47–64), E2: 58 (49–65), E3: 58 (50–65) | Plasma 25(OH)D measurement: DiaSorin Liaison 25(OH)D total assay (Immunoassay) Sample collection: 1981–1983 stored until 2009 to 2010 E1: no vit D deficiency: ≥50 nmol/L (>20 ng/mL)a
E2: vit D deficiency: ≥25 to <50 nmol/L (≥10 to 20 ng/mL) E3: serious vit D deficiency: <25 nmol/L (<10 ng/mL) | Median 21 y (Range: 0.03–30 y) until diagnosis of AD, vascular dementia, death, emigration or May 2011 | unclear |
Annweiler et al., 2011 [2], prospective cohort study, EPIDémiologie de l’OStéoporose (EPIDOS) study Toulouse (1992–1994) | France, general population, public research funding | 40 women without dementia from the EPIDOS Toulouse study Women (n): 100% (40) Age in y (median, 25./75. percentile): 78.4 (76.4/82.0) | Serum 25(OH)D measurement: Radioimmunoassay Sample collection: 1992–1994 E1: ≥25 nmol/L (≥10 ng/mL) E2: <25 nmol/L (<10 ng/mL) | 7 y | high |
Graf et al. 2014 [3], prospective cohort study | Switzerland, geriatric hospital, public research funding and material sponsorship from AstraZeneca Switzerland (2004–2005) | 246 patients, of these 200 cognitively normal, 46 with mild cognitive impairment (MCI) Women % (n): 75.6% (147 cognitively normal and 39 MCI) Age in y (mean, SD): total: n.s.; cognitively normal: 84.4 (7.1), MCI: 85.3 (6.6) | Plasma 25(OH)D measurement: Electrochemiluminescence-Immunoassay Sample collection: 2004–2005 E1: optimal vit D status: ≥75 nmol/L (≥30 ng/mL)a
E2: sub-optimal vit D status: 50–75 nmol/L (20–30 ng/mL) E3: vit D insufficiency: 25–49,9 nmol/L (10–19,96 ng/mL) E4: vit D deficiency: <25 nmol/L (<10 ng/mL) Reclassification for Meta-Analysis: e1: no vit D deficiency: ≥50 nmol/L (≥20 ng/mL) e2: vit D deficiency: ≥25 to <50 nmol/L (≥10 to 20 ng/mL) e3: serious vit D deficiency: <25 nmol/L (<10 ng/mL) | 2 y | unclear |
Knekt et al., 2014 [4], retrospective cohort study, Mini Finland Health Survey (1978–1980) | Finland, general population (population register), public research funding | 5010 subjects without hospitalisation due to dementia Women % (n): 54.7% (2738) Age in y (median): total: n.s.; E1: 54, E2: 55, E3: 56, E4: 59 | Serum 25(OH)D measurement: Radioimmunoassay (DiaSorin) Sample collection: 1978–1980 stored until 2003 E1: 4. quartile: 54–159 nmol/L (21.6–63.6 ng/mL)a
E2: 3. quartile: 40–53 nmol/L (16–21.2 ng/mL) E3: 2. quartile: 29–39 nmol/L (11.6–15.6 ng/mL) E4: 1. quartile: 7–28 nmol/L (2.8–11.2 ng/mL) | 17 y | unclear |
Littlejohns et al., 2014 [5], prospective cohort study, Cardiovascular Health Study (1992–1993) | USA, 4 communities, ambulatory participants, private and public research funding, | 1658 subjects without dementia, cardiovascular diseases or stroke Women % (n): 69.2% (1148) Age in y (median, SD): 73.6 (4.5) | Serum 25(OH)D measurement: LC-MS/MS Sample collection: 1992–1993 stored until 2008 E1: no vit D deficiency: ≥50 nmol/L (≥20 ng/mL) E2: vit D deficiency: ≥25 to <50 nmol/L (≥10 to 20 ng/mL) E3: serious vit D deficiency: <25 nmol/L (<10 ng/mL) | Average 5.6 y (SD 1.6) | unclear |
Schneider et al. 2014 [6], prospective cohort study, Atherosclerosis Risk in Communities (ARIC) Brain MRI Study (1993–1995) | USA, general population from 2 regions, public research funding | 1652 subjects (white or black ethnic background) without hospitalisation due to dementia, cardiovascular diseases or stroke Women % (n): 60.3% (996) Age in y (mean, SD): total: 62 (n.s.).; E1: Whites 63.1 (4.3); Blacks 62.2 (4.4), E2: Whites 63.3 (4.5); Blacks 61.4 (4.6), E3: Whites 62.9 (4.4); Blacks 61.0 (4.5) | Plasma 25(OH)D measurement: LC-MS/MS Sample collection: 1993–1995 stored until 2012 E1: highest tertile Whites ≥70.8 nmol/La (≥28.3 ng/mL); Blacks ≥48.3 nmol/L (≥19.3 ng/mL); E2: middle tertile: Whites 54.5 to <70.8 nmol/L (21.8 to <28.3 ng/mL); Blacks 35.0 to <48.3 nmol/L (14.0 to <19.3 ng/mL) E3: lowest tertile: Whites <54.5 nmol/L (<21.8 ng/mL); Blacks <35.0 nmol/L (<14.0 ng/mL) Reclassification for Meta-Analysis: e1: no vit D deficiency: ≥50 nmol/L (≥20 ng/mL) e2: vit D deficiency: ≥25 to <50 nmol/L (≥10 to 20 ng/mL) e3: serious vit D deficiency: <25 nmol/L (<10 ng/mL) | Median 16.6 y | unclear |
Incidence of dementia
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 |
Population: General population aged between 54 and 85.3 years (median/mean) Settings: Health examinations, geriatric hospitals Exposure/Risk: Vitamin D deficiency Comparison: No vitamin D deficiency (reference group) | ||||||
Outcomes | Comparative risk (95% CI) and narrative results | Relative effect (95% CI) | Number of participants (number of studies) | Quality of evidence (GRADE) | Comments | |
No exposure (no vitamin D deficiency) | Exposure (vitamin D deficiency) | |||||
Incidence of dementia (Results meta-analysis) Follow-up:18.03 years (weighted mean) | Study population (≥50 nmol/L or ≥ 54–159 nmol/L) | (<25 nmol/L or 7–28 nmol/L) | Point (raw) 1.54 (1.19 to 1.99) | 18 639 subjects (5 studies) | ⊕⊝⊝⊝ Very lowa,b
| |
Incidence of dementia (Narrative results) Follow-up: 7 years | Study population (≥25 nmol/L) | (<25 nmol/L) | OR 19.57 (1.11 to 343.69) | 40 subjects (1 study) |