Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The Rancho Bernardo Study

Abstract

Background Evidence of a role for vitamin D (VitD) in cognitive aging is mixed and based primarily on extreme VitD deficiency. We evaluated the association of VitD insufficiency with cognitive function in older, community-dwelling adults living in a temperate climate with year round sunshine. Methods A population-based longitudinal study of 1058 adults (median age 75; 62% women) who had cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD) measured in 1997–99 and were followed for up to three additional cognitive function assessments over a 12-year period. Results Overall, 14% (n=145) of participants had VitD insufficiency defined as 25OHD<30 ng/ml. Adjusting for age, sex, education, and season, VitD insufficiency was associated with poorer baseline performance on the Mini-Mental Status Exam (MMSE) (P=0.013), Trails Making Test B (Trails B) (P=0.015), Category Fluency (P=0.006) and Long Term Retrieval (P=0.019); differences were equivalent to 5 years of age. For those with VitD insufficiency, the odds of mildly impaired performance at baseline were 38% higher for MMSE (P=0.08), 78% higher for Trails B (P=0.017), and 2-fold higher for Category Fluency and Long Term Retrieval (both P=0.001). VitD insufficiency was not related to the rate of cognitive decline on any test or to the risk of developing impaired performance during follow-up. Conclusion In this population with little overt VitD deficiency, even moderately low VitD was associated with poorer performance on multiple domains of cognitive function. Low VitD did not predict 12-year cognitive decline. Clinical trials are essential to establish a causal link between VitD and cognitive well-being.

Low Vitamin D and Its Association with Cognitive Impairment and Dementia

“…However, most studies did not consider confounders like depression. Four studies [9,22,23,25] found no association between low serum vitamin D levels and CI and dementia in a longitudinal follow-up, whereas two studies [21,24] found a significant association (P � 0.001). However, the studies which found a significant association were smaller in size and duration of follow-up.…”

“…Nevertheless, the issue of reverse causality remains to be answered [21]. Table 1 shows a summary of evidence demonstrating an association between serum 25(OH)D, CI, and dementia [9,21,22,[23][24][25][26]. Many studies have shown an association of low vitamin D with CI at a cross-sectional level although the same studies with longitudinal follow-ups did not replicate the association [21,23,24].…”

“…Vitamin D exerts its action via VDR present in neurons, glial cells of the hippocampus, orbitofrontal-cortex, cingulate, amygdala, and thalamus [5][6][7]. Its neuroprotective, anti-inflammatory, and antioxidant effect on neurons promotes brain health [8][9][10]. Vitamin D promotes the production of neurotrophic factors such as nerve growth factor (NGF).…”

“…Vitamin D promotes the production of neurotrophic factors such as nerve growth factor (NGF). Many studies have consistently reported the increase in neuronal growth in rat hippocampal cell cultures enriched with vitamin D [8,9]. e NGF and other neurotrophic factors promote the survival of both hippocampal and cortical neurons [10,11].…”

Elizabeth Barrett-Connor: Instrumental Contributor to the Understanding of Midlife Well-being and Health in Both Women and Men

“…So much of what she pioneered is now so well established in mainstream epidemiologic research that it may be difficult to realize how groundbreaking her approach was at the time. She was one of the earliest researchers to illustrate the scientific value of examining in a population a broad range of physiologic measures and biomarkers such as glucose metabolism, sex hormones, thyroid function, and cytokines; detailed lifestyle factors including diet and physical activity; psychosocial factors such as depression, the role of social status, education, and stress; and new phenotypes including clinical measurements of eyes and bones, as well as functional health (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). She recalls that one of the comments at the time was "Why would you want to study normal people?"…”