Uric acid and late-onset Alzheimer's disease: results from the ReGAl 2.0 project.

BACKGROUND: It has been suggested that oxidative stress may have a role in the pathogenesis of Alzheimer's disease (AD). Serum uric acid (UA) could exert neuroprotective effects via its antioxidant capacities. Many studies investigated serum UA levels in subjects with AD, but to date, results are conflicting and evidence in old age subjects is weak. AIMS: In this study, we assess whether serum UA levels would be altered in the AD old age subjects compared to those of initial cognitive impairment and healthy controls. METHODS: This is a retrospective study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 232 subjects, including 65 (healthy controls HC), 95 mild cognitive impairment (MCI), and 72 AD, were included in the study. Serum UA was measured in all subjects by routine laboratory method. RESULTS: The sample population includes 232 subjects, mostly women with a mean age of 79.16 ± 5.64 (range 66-93) years. No significant difference was found in gender distribution between groups. No significant correlation was found in all populations between age and uric acid levels. AD group had significantly lower UA levels as compared with HC. The association of uric acid with AD presence after adjusting for age, gender, body mass index (BMI) and creatinine levels showed that uric acid level was independently associated with the diagnosis of AD. CONCLUSIONS: These data indicate that serum UA is reduced in AD, supporting that UA may have a potential protective role against AD in old age.

Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.

Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.

Hypovitaminosis D: A Disease Marker in Hospitalized Very Old Persons at Risk of Malnutrition.

BACKGROUND: Hypovitaminosis D is a frequent condition in elderly subjects. Vitamin D adequacy is best determined by measurement of the 25-hydroxyvitamin D-25(OH)D-concentration in the serum. An inverse association exists between 25(OH)D and cardiovascular, infectious, glucose metabolism, cognitive disorders, and all-cause mortality. Whether 25(OH)D is a marker of organ diseases is still under debate. We aimed to investigate whether comorbidities were associated with serum 25(OH)D levels in geriatric inpatients. METHODS: This is a retrospective study, including 237 subjects consecutively admitted to an acute care geriatric unit, with available data of 25(OH)D serum concentrations. 25(OH)D serum levels were defined according to the following cutoffs: 50⁻30 ng/mL (125⁻75 nmol/L): optimal range; 30⁻20 ng/mL (75⁻50 nmol/L): insufficiency; 20⁻10 ng/mL (5⁻25 nmol/L): deficiency; and <10 ng/mL (<25 nmol/L): severe deficiency. Comorbidity was assessed using the Cumulative Illness Rating Scale-Geriatric (CIRS-G). Two summary measures were obtained, the Illness Severity Index (CIRS-SI) and the Comorbidity Index (CIRS-CI). RESULTS: 177 (74.68%) women and 60 (25.32%) men with mean age of 85 ± 6 years old were enrolled. The majority of subjects (68.6%) were at risk of malnutrition. Overall, the burden of comorbidity was 1.87 ± 1.33 for CIRS-CI and 1.18 ± 0.40 for CIRS-SI. 25(OH)D serum concentrations were 10.58 ± 7.68 ng/mL, with 98.7% of subjects having vitamin D below 30 ng/mL and 56.6% with severe deficiency. An inverse correlation was found between 25(OH)D and both CIRS-SI (r: -0.312; p < 0.0001) and CIRS-CI (r: -0.306; p < 0.0001). Independent of multiple covariates an inverse association between both CIRS-SI (p < 0.0001) and CIRS-CI (p < 0.0001) and 25(OH)D was confirmed. Both CIRS-SI (r = 0.251, p < 0.0001) and CIRS-CI (r = 0.137, p = 0.016) were positively correlated with the length of hospital stay. An inverse correlation was confirmed between serum 25(OH)D concentrations and CRP (r = -0.142; p = 0.041). CRP, in turn, positively correlated with CIRS-SI (r = 0.209, p = 0.003) and CIRS-CI (r = 0.158, p = 0.023). Both CIRS-SI (r = 0.251, p < 0.0001) and CIRS-CI (r = 0.137, p = 0.016) were positively correlated with the length of hospital stay. CONCLUSIONS: In hospitalized very old subjects, a higher comorbidity burden is associated with lower 25(OH)D serum levels. Hypovitaminosis D was correlated with higher inflammatory status, which, together with the comorbidities burden, negatively influenced the length of hospital stay.