Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

This is the final version of the article. Available from Wiley via the DOI in this record.BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.This work was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust and Newcastle University (AG). The Newcastle 85+ Study has been funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council and the Dunhill Medical Trust. Additional work has also been funded by the British Heart Foundation, Unilever Corporate Research, Newcastle University and National Health Service (NHS) North of Tyne (Newcastle Primary Care Trust). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service, UK. We acknowledge the operational support of NHS North of Tyne, the local general practitioners and their staff, the research nurses, laboratory technicians, data management and clerical team, as well as many colleagues for their expert advice. Thanks are due especially to the study participants

A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma

Ultraviolet radiation exposure increases basal cell carcinoma (BCC) risk, but may be protective against prostate cancer. We attempted to identify exposure patterns that confer reduced prostate cancer risk without increasing that of BCC. We used a questionnaire to assess exposure in 528 prostate cancer patients and 442 men with basal cell carcinoma, using 365 benign prostatic hypertrophy patients as controls. Skin type 1 (odds ratio (OR)=0.47, 95% CI=0.26–0.86), childhood sunburning (OR=0.38, 95% CI=0.26–0.57), occasional/frequent sunbathing (OR=0.21, 95% CI=0.14–0.31), lifetime weekday (OR=0.85, 95% CI=0.80–0.91) and weekend exposure (OR=0.79, 95% CI=0.73–0.86) were associated with reduced prostate cancer risk. Skin type 1 (OR=4.00, 95% CI=2.16–7.41), childhood sunburning (OR=1.91, 95% CI=1.36–2.68), regular foreign holidays (OR=6.91, 95% CI=5.00-9.55) and weekend (OR=1.17, 95% CI=1.08–1.27) but not weekday exposure were linked with increased BCC risk. Combinations of one or two parameters were associated with a progressive decrease in the ORs for prostate cancer risk (OR=0.54–0.25) with correspondingly increased BCC risk (OR=1.60–2.54). Our data do not define exposure patterns that reduce prostate cancer risk without increasing BCC risk

The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: Role of the renin angiotensin system inhibition

<p>Abstract</p> <p>Background</p> <p>Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC), to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide) in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments.</p> <p>Methods/Design</p> <p>The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older) with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control") for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP < 140 mm Hg and DBP < 90 mm Hg. Additional antihypertensives are added to achieve this goal if needed. Eligible participants are those with hypertension, defined as a blood pressure 140/90 mm Hg or greater, early cognitive impairment without dementia defined (10 or less out of 15 on the executive clock draw test or 1 standard deviation below the mean on the immediate memory subtest of the repeatable battery for the assessment of neuropsychological status and Mini-Mental-Status-exam >20 and without clinical diagnosis of dementia or Alzheimer's disease). Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives), 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory), cerebral blood flow, and carbon dioxide cerebral vasoreactivity.</p> <p>Discussion</p> <p>The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the threshold of dementia. Success of this trial will offer new therapeutic application of antihypertensives that inhibit the renin angiotensin system and new insights in the role of this system in aging.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00605072</p

Computerized Psychometric Testing in Minimal Encephalopathy and Modulation by Nitrogen Challenge and Liver Transplant

Background &amp; Aims: A lack of standardized tests was cited by hepatologists for not testing for minimal hepatic encephalopathy. We therefore compared paper and pencil neuropsychologic tests with a comprehensive computerized assessment (Cognitive Drug Research [CDR], Goring-on-Thames, United Kingdom) of cognitive function. Methods: Eighty-nine cirrhotic patients were studied. Composite scores were calculated from the CDR subtests to reflect 5 cognitive domains, and results were validated by comparison with those from 6 standard paper and pencil tests. Level of impairment was defined using the sum of the standard deviations by which each CDR domain (CDR factor score [CDRS]) and each paper and pencil test score (PHES) differed from age-matched norms. CDRS and PHES were repeated in 21 patients after liver transplantation and CDRS in 24 patients after a 108-g amino acid challenge. Results: There was a high correlation between the 2 assessment methods (r = 0.748; P = .001). Using multiple regression, Model of End-Stage Liver Disease score (P = .011) correlated with PHES. In contrast, the CDR domains Continuity of Attention and Quality of Episodic Memory were significantly related to venous blood ammonia levels (adjusted R-2 = 0.200; F-6,F-76 = 4.41; P = .001). There were marked deteriorations in the CDR composite scores representing Accuracy of Working (P = .005) and Episodic Memory (P = .001) after amino acid challenge when blood ammonia increased from 63 +/- 36 to 126 +/- 62 mu mol/L (P = .001). Both PHES and CDRS returned to the control range after liver transplantation (PHES: pretransplantation, -6; posttransplantation, 0; P &lt; .001; CDRS: pretransplantation, -6; posttransplantation, -2; P = .003). Conclusions: CDRS is valuable for the recognition of minimal hepatic encephalopathy