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Table 1 Characteristics of included studies

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

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

  1. Abbreviations: AD Alzheimer’s disease, nmol/L nanomoles per litre, ng/mL nanograms per millilitre, SD standard deviation, Vit D Vitamin D, n number, n.s. not specified, E or e exposure, y years, LC-MS liquid chromatography-tandem mass spectrometry, MCI mild cognitive impairment
  2. aTo convert 25(OH)D to nanomoles per litre from nanograms per litre, multiply values by 2.5