Severe Vitamin D Deficiency Is Associated With Advanced‐stage Dementia in Geriatric Inpatients

To the Editor: Vitamin D is a neurosteroid hormone with neuroprotective and vasculoprotective effects in the central nervous system (CNS).1,2 Age-related hypovitaminosis D has been recently associated with impaired global cognitive function in older adults,3 with twice the risk of cognitive impairment for low vitamin D status as for normal status.4–6 It remains unclear whether hypovitaminosis D is associated with dementia and its degree of progress. The objective of the current study was to examine the association of severe serum 25-hydroxyvitamin D deficiency (25OHD <10 ng/mL) with advanced-stage (moderately severe to severe) dementia in geriatric inpatients, taking all potential confounders into account. Between June and November 2008, a standardized cognitive assessment was obtained from all patients admitted to the geriatric acute care unit of Angers University Hospital, Angers, France, after obtaining informed consent or the agreement of a trusted person, as appropriate. The diagnosis of dementia was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,7 whatever the etiology, and after exclusion of confused patients identified using the Confusion Assessment Method.8 Moderately severe to severe stages were defined as a Folstein Mini-Mental State Examination (MMSE) score less than 15 out of 30.9 The number of acute diseases (with sudden onset and rapid progression) and chronic diseases (of indefinite duration or running a course with minimal change) and supine pulse pressure (PP) were assessed on admission to the care unit. In addition, a systematic health status questionnaire focused on the use of psychoactive drugs (benzodiazepines, antidepressants, neuroleptics), morphine, and corticoids. Fasting early morning venous blood was collected after rehydration from resting subjects for the measurement of serum 25OHD, intact parathyroid hormone (iPTH), albumin, and creatinine. Severe vitamin D deficiency was defined as serum 25OHD less than 10 ng/mL10 (to convert to nmol/L, multiply by 2.496). Estimated creatinine clearance was calculated using the Cockcroft formula. The study was conducted in accordance with the ethical standards set by the Helsinki Declaration (1983). The local ethical committee approved the entire study protocol. Univariate and multivariate (fully adjusted and backward stepwise methods) logistic regression analyses were performed to specify the association between severe 25OHD deficiency and moderately severe to severe dementia. Age; sex; PP; number of acute and chronic diseases; use of psychoactive drugs, morphine, and corticoids; and serum iPTH, albumin, and creatinine clearance were used as potential confounders. P<.05 was considered to be statistically significant. All analyses were performed using SPSS version 17.0 (SPSS, Inc., Chicago, IL). In the 288 older adults included (mean age 86.0±0.4; 66.1% female; 100% Caucasian; mean PP 60.1±1.2 mmHg; 2.9±0.1 acute and 3.7±0.1 chronic diseases), mean serum 25OHD concentration was 14.1±0.5 ng/mL, and iPTH was 67.2±2.7 pg/mL. Thirty-three percent of the sample exhibited some degree of moderately severe to severe dementia. Participants with severe 25OHD deficiency (n=138) more often had moderately severe to severe dementia than those with normal 25OHD concentrations (n=150) (42.5% vs 25.2%, P=.01). Severe 25OHD deficiency was significantly associated with moderately severe to severe dementia (unadjusted odds ratio (OR)=2.22, P=.01; adjusted OR=2.57, P=.04 for fully adjusted model) and remained the only characteristic associated with moderately severe to severe dementia in the stepwise backward model (OR=2.39, P=.02) (Table 1). These results showed that severe 25OHD deficiency, irrespective of potential confounders, was the main characteristic associated with moderately severe to severe dementia in geriatric inpatients. This finding was in line with the emerging literature, which highlights a significant positive association between serum 25OHD concentration and global cognitive function.1–6 The results were also in accordance with a previous study that recently showed a significant adjusted association between serum vitamin D insufficiency (≤20 ng/mL) and Alzheimer's disease (OR=2.51, P=.04) in a cohort of 318 older home-based subjects (mean age 73.5±8.1, 72.6% female).5 The fact that vitamin D is a neurosteroid hormone involved in physiological CNS function through the regulation of neurotransmitters such as acetylcholine1 as well as the regulation of neurotrophic factors including nerve growth factor1,2 could explain these findings. In addition, neuroprotective properties have been described, including the regulation of inflammation, oxidative stress, and ischemic lesions,1,2 which are pathophysiological mechanisms typically involved in the natural history of dementia. It is thus possible that the lower the serum 25OHD concentration, the less the CNS works and is protected, and the more severe the dementia is. Nevertheless, the cross-sectional design of the current study limits the exploration of the association between severe 25OHD deficiency and moderately severe to severe dementia and does not allow any causal inference, such as with a prospective cohort design. Further research is needed to corroborate and explain these results. The authors wish to thank Angers University Hospital for technical support. Conflict of Interest: Dr. Annweiler serves as a consultant for Ipsen Pharma company. He has no relevant financial interest in this manuscript. Prof. Schott serves as a consultant for Ipsen Pharma company and as a board member for Osteoporosis International. She has no relevant financial interest in this manuscript. Prof. Berrut serves as a board member for Annales de Gérontologie. He has no relevant financial interest in this manuscript. Prof. Beauchet serves as a consultant for Ipsen Pharma company and as a board member for Annales de Gérontologie. He has no relevant financial interest in this manuscript. Authors Contribution: Annweiler had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. Study concept and design: Annweiler and Beauchet. Acquisition of data: Annweiler and Beauchet. Analysis and interpretation of data: Annweiler, Fantino and Beauchet. Drafting of the manuscript: Annweiler and Beauchet. Critical revision of the manuscript for important intellectual content: Fantino, Le Gall, Schott, and Berrut. Statistical expertise: Annweiler. Administrative, technical, or material support: Annweiler and Beauchet. Study supervision: Beauchet. Sponsor's Role: None.