Vitamin D status is associated with executive function a decade later: Data from the Women's Healthy Ageing Project.

OBJECTIVES: Vitamin D deficiency has been associated with cognitive decline and dementia in older adults. However, there is a paucity of studies assessing whether this association manifests from midlife. Given the long prodromal stage of dementia, we investigated the association between midlife vitamin D and cognition 10 years later. STUDY DESIGN: 252 participants (aged 55-67 years) from the Women's Healthy Ageing Project had baseline (2002) vitamin D and neuropsychological measures assessed. Of these, 170 (aged 65-77 years) had follow-up neuropsychological testing (2012). OUTCOME MEASURES: Serum 25-hydroxyvitamin D (25[OH]D) was measured using an automated chemiluminescence system. The neuropsychological tests used were: Consortium to Establish a Registry for Alzheimer's Disease (CERAD), California Verbal Learning Test Second Edition (CVLT-II), verbal fluency and Trail Making Test-B (TMT-B). Composite scores for verbal episodic memory (CERAD and CVLT-II) and executive function (verbal fluency and TMT-B) were obtained by summating standardized scores for each test. RESULTS: Analyses were adjusted for age, education and body mass index (BMI). Further adjustment for physical activity, depression, vascular risk factors, supplementation and APOE4-genotype did not materially change the results. At baseline, those with vitamin D>25nmol/L performed better on verbal fluency (ß=2.46, 95%CI=0.53,4.40) and TMT-B time (ß=-18.23, 95%CI=-32.86,-3.61), with higher executive function (ß=1.40, 95%CI=0.44,2.37). These relationships persisted 10 years later for TMT-B (ß=-15.38, 95%CI=-30.82,0.07) and executive function (ß=1.05, 95%CI=0.14,1.95). There were no associations with tests of verbal episodic memory. CONCLUSION: Midlife vitamin D>25nmol/L is associated with improved aspects of executive function in ageing. Findings highlight a potential therapeutic age window where midlife vitamin D repletion could be neuroprotective against cognitive decline.

A Systematic Review and Meta-Analysis of The Effect of Low Vitamin D on Cognition.

BACKGROUND/OBJECTIVE: With an aging population and no cure for dementia on the horizon, risk factor modification prior to disease onset is an urgent health priority. Therefore, this review examined the effect of low vitamin D status or vitamin D supplementation on cognition in midlife and older adults without a diagnosis of dementia. DESIGN: Systematic review and random effect meta-analysis. SETTING: Observational (cross-sectional and longitudinal cohort) studies comparing low and high vitamin D status and interventions comparing vitamin D supplementation with a control group were included in the review and meta-analysis. PARTICIPANTS: Studies including adults and older adults without a dementia diagnosis were included. MEASUREMENTS: Medline (PubMed), AMED, Psych INFO, and Cochrane Central databases were searched for articles until August 2016. The Newcastle-Ottawa Scale and Physiotherapy Evidence Database assessed methodological quality of all studies. RESULTS: Twenty-six observational and three intervention studies (n = 19-9,556) were included in the meta-analysis. Low vitamin D was associated with worse cognitive performance (OR = 1.24, CI = 1.14-1.35) and cognitive decline (OR = 1.26, CI = 1.09-1.23); with cross-sectional yielding a stronger effect compared to longitudinal studies. Vitamin D supplementation showed no significant benefit on cognition compared with control (SMD = 0.21, CI = -0.05 to 0.46). CONCLUSION: Observational evidence demonstrates low vitamin D is related to poorer cognition; however, interventional studies are yet to show a clear benefit from vitamin D supplementation. From the evidence to date, there is likely a therapeutic age window relevant to the development of disease and therefore vitamin D therapy. Longitudinal lifespan studies are necessary to depict the optimal timing and duration in which repletion of vitamin D may protect against cognitive decline and dementia in aging, to better inform trials and practice towards a successful therapy.

Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts.

BACKGROUND: Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. OBJECTIVE: To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. METHODS: Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. RESULTS: Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04). CONCLUSIONS: High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

Increased risk of cognitive impairment in patients with diabetes is associated with metformin.

OBJECTIVE: To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODS: Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22). RESULTS: Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]). CONCLUSIONS: Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.