Vitamin D and All-Cause Dementia in the Cardiovascular Health Study Dr Maya Soni AAIC Boston, July 2013 No conflicts of interest to declare
Previous research Meta-analyses Lower vitamin D levels in AD 1 Poorer MMSE scores associated with vit D deficiency 1 Higher risk of cognitive impairment with vitamin D deficiency 2 Prospective studies Cognitive decline in older Europeans (RR = 1.6) 3 Cognitive decline in older women (OR = 1.6, 1.3) 4 Incident dementia of non-alzheimer s type but not AD (note: n=40) 5 Vitamin D3, cholecalciferol 1 Balion et al. 2012; 2 Etgen et al. 2012; 3 Llewellyn et al. 2010; 4 Slinin et al. 2012; 5 Annweiler et al. 2011
Potential mechanisms Neurodegenerative Amyloid breakdown/ clearance 1 Age related cognitive decline in rats 2 Cellular environment Calcium homeostasis 6 Nerve conduction 7 Axon growth 8 Inflammation 9 Vascular effects Renin-angiotensin system 3 Atherosclerotic plaques 4 Protective against stroke 5 1 Masoumi et al, J Alzheimer s Dis 2009, 17(3), 703-17; 2 Briones & Darwish, J Neuroinflammation 2012, 9, 244-256; 3 Kestenbaum et al, JACC 2011, 58(14), 1433-41; 4 de Boer et al, J Am Soc Nephrol 2009; 5 Buell et al, Neurology 2010, 74(1), 18-26; 6 Brewer et al, Cell Calcium 2006, 40(3), 277-86; 7 Cai et al, Cell Calcium 1994, 15, 401-10; 8 Chabas et al, J Neurotrauma 2008, 25(10), 1247-56; 8 Villaggio et al, Clin Exp Rheumatol 2012, 30(6), 934-8
Vitamin D and all-cause dementia in the CHS Ambulatory older adults free from dementia, clinical CVD/stroke 25(OH)D measured (LC-MS) in 1992 93 Adjudicated dementia status (DSM-IV) over mean 5.6 years (SD 1.6) Cox proportional hazards models Adjusted for age, season of blood collection, sex, education, BMI, alcohol consumption and depressive symptoms
Inclusion in final sample 3,268 Blood draw for vitamin D assay 2,323 2,254 1,658 1,653 945 (insufficient serum) 69 (prevalent dementia) 596 (no adjudicated dementia status) 5 (missing education/alcohol data) Final restricted sample
Loss to follow up Included participants Lost to follow up Mean age in years (SD) 73.6 (4.5) 74.3 (5.4).005 Education %.02 Did not finish high school 22.1 27.4 Finished high school/some college/vocational 54.9 53 Finished college/professional 22.9 19.6 Non-white % 19.8 12.3 <.001 Serum 25(OH)D nmol/l (SD) 65.1 (26.5) 61.1 (39.5).007 p
Prevalent all-cause dementia 1,727 participants, 69 with dementia at baseline 10 Relative risk 5 0 <25 25-<05 25(OH)D, nmol/l P for trend = <0.001 Adjusted for age, season of vitamin D collection, education, sex, BMI, alcohol consumption, depressive symptoms
Incident all-cause dementia 171 people developed all-cause dementia over a mean of 5.6 years Hazard ratio for all-cause dementia 0 1 2 3 4 5 <25 25-49 >=50 Serum 25(OH)D (nmol/l) Vitamin D status (nmol/l) P for trend = 0.002 % of cohort Sufficient ( 50) 70.66 Deficient ( 25 to <50) 25.17 Severely deficient (<25) 4.17 Adjusted for age, season of vitamin D collection, education, sex, BMI, alcohol consumption, depressive symptoms
Incident all-cause dementia Sensitivity analyses: Excluding >200nmol/L 3 or 4 groups vitamin D Preliminary analysis, unadjusted model
Conclusions
Acknowledgements University of Exeter Medical School Dr David Llewellyn Dr Iain Lang Mr Tom Littlejohns Dr Elzbieta Kuzma Dr Katarina Kos Professor William Henley International collaborators Dr Cedric Annweiler Professor Olivier Beauchet Dr Paulo Chaves Professor Linda Fried Professor Bryan Kestenbaum Professor Lewis Kuller Professor Kenneth Langa Professor Oscar Lopez The Cardiovascular Health Study The Alzheimer s Association (NIRG-11-200737, travel fellowship)
Thank you m.soni@exeter.ac.uk
Sensitivity analysis: vitamin D<200 nmol/l Dementia status All-cause dementia Serum 25(OH)D, nmol/l 50 25 to <50 <25 HR (95% CI) HR (95% CI) p-value for linear trend Model A 1 1.49 (1.05-2.13) 2.24 (1.24-4.05) 0.002 Model B 1 1.50 (1.04-2.16) 2.28 (1.24-4.17) 0.002 Model A: adjusted for age and season of vitamin D collection Model B: adjusted for Model A and education, sex, BMI, alcohol consumption and depressive symptoms Abbreviations: HR = Hazard ratio, CI = Confidence interval
Sensitivity analysis: vitamin in 4 categories Dementia status Serum 25(OH)D, nmol/l 75 50 to <75 25 to <50 <25 HR (95% CI) HR (95% CI) HR (95% CI) p for linear trend Model A 1 0.87 (0.60-1.28) 1.41 (0.93-2.12) 2.07 (1.10-3.90) 0.018 Model B 1 0.80 (0.54-1.18) 1.32 (0.86-2.02) 1.98 (1.03-3.80) 0.042 Model A: adjusted for age and season of vitamin D collection Model B: adjusted for Model A and education, sex, BMI, alcohol consumption and depressive symptoms Abbreviations: HR = Hazard ratio, CI = Confidence interval
Results: Vitamin D and prevalent Alzheimer s disease AD status Serum 25(OH)D, nmol/l 50 25 to <50 <25 OR (95% CI) OR (95% CI) p-value for linear trend Model A 1 1.80 (0.82-3.95) 4.02 (1.35-11.97).01 Model B 1 1.65 (0.71-3.81) 3.54 (1.11-11.29).03 Model A: adjusted for age and season of blood collection Model B: adjusted for Model A and education, sex, BMI, alcohol consumption and depressive symptoms Abbreviations: OR = Odds Ratio, CI = Confidence Interval
Results: Vitamin D and incident Alzheimer s disease AD status Serum 25(OH)D, nmol/l 50 25 to <50 <25 HR (95% CI) HR (95% CI) p-value for linear trend Model A 1 1.67 (1.06-2.62) 2.29 (1.07-4.88).005 Model B 1 1.64 (1.03-2.60) 2.23 (1.03-4.82).009 Model A: adjusted for age and season of blood collection Model B: adjusted for Model A and education, sex, BMI, alcohol consumption and depressive symptoms Abbreviations: HR = Hazard Ratio, CI = Confidence Interval
Incident dementia in the CHS: baseline characteristics I Baseline characteristics Sufficient Insufficient Deficient Severely 50 to <75 25 to <50 deficient 75 nmol/l nmol/l nmol/l <25 nmol/l p Age (y), M(SD) 73.33 (4.15) 73.75 (4.58) 73.78 (4.53) 74.07 (5.17) 0.270 White race (%) 96.58 90.19 77.16 60.87 < 0.001 Women (%) 57.79 70.25 78.85 89.86 < 0.001 Education 0.026 Did not finish high school 17.49 23.52 24.76 28.99 Finished high school/some 56.08 54.36 54.09 56.52 college/vocational College/professional 26.43 22.12 21.15 22.93 Current smoker % (n=1,615) 8.58 7.83 11.00 14.93 0.117 BMI (kg/m 2 ), M(SD) 25.54 (3.99) 26.49 (4.26) 27.62 (5.10) 27.54 (5.20) < 0.001
Incident dementia in the CHS: baseline characteristics II Baseline characteristics Sufficient Insufficient 50 to <75 Deficient 25 to <50 Severely deficient 75 nmol/l nmol/l nmol/l <25 nmol/l p Season tested (%) < 0.001 Dec-Feb 13.69 21.03 31.49 33.33 Mar-May 13.31 21.34 34.38 44.93 Jun-Aug 37.45 32.71 14.42 11.59 Sep-Nov 35.55 24.92 19.71 10.14 Alcohol use (%) a 0.082 Non-drinkers 49.24 54.98 58.41 57.97 Moderate drinkers 40.11 37.54 34.86 34.78 Heavy drinkers 10.56 7.48 6.73 7.25
Incident dementia in the CHS: baseline characteristics III Baseline characteristics Sufficient Insufficient 50 to <75 Deficient 25 to <50 Severely deficient 75 nmol/l nmol/l nmol/l <25 nmol/l p MRI evidence of stroke (%) 24.71 25.39 24.52 37.68 0.123 Diabetes (%) b 7.22 8.72 15.38 23.19 < 0.001 Hypertension c 0.003 Normal 46.20 44.08 35.82 27.54 Treated 17.68 18.69 23.80 28.99 Untreated 36.12 37.23 40.38 43.48 Impaired kidney function d 21.67 15.58 17.79 21.74 0.050 Depression e 18.06 19.47 27.88 30.43 < 0.001 1 APOE allele (n=1,518) 24.22 22.80 26.56 30.51 0.396 Years of follow up M(SD) 5.67 (1.03) 5.63 (1.12) 5.44 (1.37) 5.56 (1.23) 0.025
Baseline vitamin D in the CHS Density 0.005.01.015.02 0 100 200 300 vd5_nmol Vitamin D status (nmol/l) % of cohort Sufficient ( 50) 70.66 Deficient ( 25 to <50) 25.17 Severely deficient (<25) 4.17 University of Exeter Medical School, UK