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Vitamin D, Physical Performance and Neuropsychological Functioning in Elderly Subjects:The Pro.V.A Study

Year: 2013
Type: dissertation
Study design: Observational Study
Abstract: BACKGROUND In the past two decades, it has become evident that the role of vitamin D extends beyond calcium homoeostasis.1 Vitamin D metabolites have been found to affect muscle metabolism by stimulating de novo protein synthesis, increasing the proportion of type II muscle fibers and improving muscle function.2 Moreover Vitamin D receptors seem to be widespread in brain tissue and vitamin D’s biologically active form (1,25OHD3) has shown neuroprotective effects including the clearance of amyloid plaques.3 Clinical studies on older people have shown that low serum levels of 25-hydroxyvitamin D (25OHD) correlate with poorer motor performances and with cognitive decline.4-10 Therefore the association between vitamin D, performance tests exploring mobility impairments and neuropsychological test exploring both cognitive and depression mood in elderly subjects has become a clinically hot topic. The purpose of the study was to verify the association between vitamin D status and motor and neuropsychological functioning in a large sample of Italian older people. SPECIFIC AIMS OF THE STUDY The following aims have been taken into considerations: 1. testing the relationship between 25OHD serum levels and a large battery of physical performance tests (exploring balance, gait speed, coordination, upper and lower limb strength and aerobic capacity) and identify 25OHD serum levels optimal for mobility performance 2. to explore the association between baseline serum levels of 25OHD and the 4y subsequent cognitive decline 3. to explore the association between baseline serum levels of 25OHD and the 4y subsequent development of depression mood. METHODS Data for this analysis are from the Progetto Veneto Anziani (Pro.V.A.).11 The sample consisted of community-dwelling elderly men and women whose data on physical performance, cognitive and psychological evaluation were complete. Motor performance assessment: Physical performances were evaluated using the following standardized tests:11  Tandem test, TT (static balance ability): participants were asked to maintain balance in three different positions: a side-by-side position, a semi tandem position, and a full-tandem position. The amount of time they succeeded in remaining so, in seconds, was recorded;  5 timed chair stands, TCS (coordination and strength): participants were asked to stand up and sit down 5 times as quickly as possible, with their hands folded across their chest; the time taken to complete the test, in seconds, was recorded;  Gait speed, GS: the best performance achieved in two walks at usual pace along a 4m corridor was recorded in meter/seconds. Participants were allowed to use canes or walkers;  6-minute walking test, 6mW (aerobic capacity): participants were asked to walk at their usual pace for 6 minutes, recording the distance they covered in meters;  Handgrip and quadriceps strength: handgrip strength, in kg, was measured using a JAMAR hand-held dynamometer (BK-7498, Fred Sammons, Inc.). Knee extensor (quadriceps) and hip flexor (iliopsoas) muscle strengths were determined using a Nicholas Manual dynamometer (BK-7454, Fred Sammons, Inc.). Neuropsychological Functioning Assessment: Cognitive function was evaluated at baseline and at follow-up, by administering the 30-item Mini Mental State Examination, according to Folstein.12 This test is the most widely and validated neuropsychological tool to measure cognitive function in geriatric setting. Diagnosis of dementia was performed by geretricians and psychologists with expertise in cognitive impairment according to criteria set out in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).13 Depression was evaluated by using the Geriatric Depression Scale, and a score of ≥11 was indicative of depressive symptoms.14 Statistical analysis All statistical analysis were performed using the SAS rel. 9.13 (Cary NC: SAS institute), and a two-tailed p-value <.05 was assumed for statistical significance. Participants’ characteristics were summarized using means (± standard deviations) for continuous variables and counts and percentages for categorical variables. Means and proportions were calculated for sex-specific quintiles and tertiles of the distribution of 25OHD serum levels or for vitamin D clinical cut-off values (deficient <50 nmol/L, insufficient >50 and <75 nmol/L, sufficient >75 nmol/L).15 Differences in categorical variables were examined using the Chi-square test. Age-adjusted p values for trends were calculated, checking the differences between means of covariates by quintiles/tertiles or clinical cut-offs values of vitamin D using analysis of variance (ANOVA). General linear models (GLM) were used to examine the independent association between 25OHD levels and performance tests or neuropsychological function. Known factors associated with 25OHD levels and/or physical/cognitive functionality were examined for inclusion in the analyses and multivariate models were obtained. To identify the best 25OHD levels for musculoskeletal functions in the elderly men and women, we conducted a loess analysis. Longitudinal analysis were performed for motor performance test significantly associated to vitamin D status at baseline. Multivariate logistic regression models were used to determine the relationship of serum 25OHD levels to substantial cognitive decline, defined as a decline in MMSE score of 3 or more points at follow-up. Random-effects models were applied to examine the association between serum 25(OH)D levels and the mean 4y changing in MMSE scores. Cox-regression models were obtained to identify predictors of depression onset at follow-up. RESULTS The baseline study population consisted of 2694 community dwelling older people: 1597 women with a mean age 75.6 y ±7.5 (range 65-98 y) and 1097 men with a mean age 76.2 y ±7.8 (range 65-99). The mean serum 25OHD level was 65.0 nmol/L (±41.3; range: 2.5-329) in women, and 101.9 nmol/L (±62.4; range: 2.5-441) in men. Vitamin D deficiency (25OHD level <50 nmol/L [12]), was present in the 40% of the women and in the 20% of the men; severe deficiency (25OHD <25 nmol/L; [13]) was identified in 13.5% of women and 5.9% of men. Among the 2694 community dwelling elderly enrolled at baseline, a total of 1904 participants completed the follow-up cognitive assessment between 1999 and 2001 and were included in the analysis for cognitive decline (mean [SD] follow-up, 4.4 [1.1] years), whereas a total of 1675 (363M/ 1039F, age 65-99 y ) completed the follow-up GDS assessment and were included in the analyses for depression risk. Association between 25OHD levels and performance measure Significant linear associations were found for TCS test (p for trend <.0001 in women; .03 in men), gait speed and 6mW test (p for trend <.0001, in both genders), and for handgrip strength (p for trend <.0009 in women; <.0001 in men). After controlling for confounders and covariates, a significant linear trend was still evident for the 6mW test in both genders (p=.0002 in women; <.0001 in men), for the TCS test in women (p=.004), and for gait speed (p=.0006) and handgrip strength (p=.03) in men, as shown in Table 1a and 1b. The association between 25OHD concentrations and performance measures is shown for TCS, gait speed, 6mW distance and handgrip strength tests in Figure 1a,b,c, and d respectively. The time taken to complete the TCS test decreased significantly with increasing levels of 25OHD in women only and most of the improvements occurred between 20 to 100 nmol/L of 25OHD. In men but not in women, gait speed increased significantly for 25OHD levels up to 100 nmol/L, most of the improvement occurring at concentrations ranging from 50 to approximately 75 nmol/L. Handgrip strength improved in men with increasing level of vitamin D up to 100 nmol/L. The 6mW distance continued to increase up to 25OHD serum levels of 100 nmol/L in both genders. No further significant improvements in these four motor performances were seen for 25OHD levels >100 nmol/L, in both genders. Association between 25OHD levels and longitudinal cognitive decline and risk for depression In logistic regression models adjusted only for the baseline MMSE score, participants who were 25(OH)D deficient (<50 nmol/l) or insufficient (>50-<75) were more likely than those who were 25(OH)D repleted to have a 4y substantial cognitive decline on the MMSE scores (Table 2). This association was attenuated but remained significant after controlling for covariates in the deficient 25OHD group only, whereas it was no longer significant in the insufficient 25OHD group. Participants with a 25(OH)D deficiency were approximately 40% more likely than those 25(OH)D sufficient to experience a substantial cognitive decline on the MMSE score at follow-up. Restricting the sample to participants who were non-demented at baseline (Table 3), the association between 25OHD levels and cognitive decline was even more evident. Participants with both 25OHD deficiency and insufficiency were at higher risk for cognitive decline at 4y. In random-effects models adjusted for baseline MMSE score only, those who were 25OHD deficient experienced a decline in cognitive test about twice that observed in participant 25OHD sufficient (Table 4). In fully adjusted models, participants with 25OHD deficiency declined by 0.59 MMSE points more than participants who were 25OHD sufficient. The increased rate of decline for those who were 25OHD deficient was statistically significant, as was the linear trend across groups. The same pattern of associations was observed when we restricted the sample to participants who were non-demented at baseline, even though the amount of the decline and the differences between levels of 25OHD were slightly lower than those observed in all participants. At Cox regression analysis, no association were found between Vitamin D status and the subsequent risk of depression mood at 4 years (Table 5). CONCLUSION
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W2276846476
Cites: 89
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