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

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, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 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.

Cerebral microglial activation in patients with hepatitis C: in vivo evidence of neuroinflammation.

Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, (11)C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers. Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment. PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls (P = 0.03). The caudate and thalamic binding potential were more significantly increased in six patients with genotype 1 infection (P = 0.007) and positively correlated with viraemia (r = 0.77, P = 0.005). Basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls (P = 0.0004 and P = 0.01, respectively). Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C. This provides further in vivo evidence for a neurotropic role for HCV.

Impact of hypertension and apolipoprotein E4 on poststroke cognition in subjects >75 years of age.

BACKGROUND AND PURPOSE: The apolipoprotein E4 allele (APOE4) associates with increased dementia risk, and hypertension may associate with mild cognitive deficits. We examined whether nondemented stroke patients with (1) a prestroke history of hypertension and (2) APOE4 were more cognitively impaired at 3 months after stroke. METHODS: A total of 257 participants were genotyped and outcomes from neuropsychological evaluations analyzed using regression. RESULTS: Total Cambridge Assessment for Mental Disorders in the Elderly (CAMCOG) and speed of working memory significantly associated with hypertension. No outcomes significantly associated with APOE4. CONCLUSIONS: Subjects with prestroke hypertension had more impaired global cognition and slower access to information held in working memory.

Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial.

BACKGROUND: Hypertension is associated with impaired cognitive function but the effect of antihypertensive treatment on cognitive function is unclear. METHODS: We investigated the effect of treatment of hypertension on cognition with the angiotensin-receptor-blocker, candesartan, in a placebo-controlled, double-blind, randomized controlled trial at one center participating in the Study on Cognition and Prognosis in the Elderly. A total of 257 older adults with hypertension (mean age 76 years, blood pressure 165 +/- 8/88 +/- 7 mm Hg) were recruited from general practice and treated with 8-16 mg candesartan or placebo once daily, for a mean follow-up period of 44 months. Additional antihypertensive therapy was permitted in both groups to achieve treatment targets. Cognitive function was measured using the Cognitive Drug Research computerized assessment battery, trail-making tests, and verbal fluency. Data from annual assessments were used to calculate individual coefficients of decline by regressing composite test scores over time for five cognitive domains. RESULTS: The blood pressure difference between groups at study close was 8/3 mm Hg. The candesartan group showed less decline in attention (0.004 vs -0.036, p = 0.04) and episodic memory (0.14 vs -0.22, p = 0.04) compared to placebo, a similar trend for speed of cognition (-2.3 vs -17.4, p = 0.15), but no differences in working memory (0.0014 vs 0.0010, p = 0.90) or executive function (-0.0031 vs -0.0023, p = 0.95). Effect sizes were in the small-to-moderate range. CONCLUSIONS: The potential for blood pressure-lowering with angiotensin-receptor-blockers to reduce the rate of decline of specific areas of cognitive function in older patients with hypertension warrants further investigation to determine clinical efficacy.

Cognitive performance in hypertensive and normotensive older subjects.

Longitudinal studies suggest that hypertension in midlife is associated with cognitive impairment in later life. Cross-sectional studies are difficult to interpret because blood pressure can change with onset of dementia and the inclusion of subjects on treatment and with hypertensive end-organ damage can make analysis difficult. We examined cognitive performance in hypertensive and normotensive subjects without dementia or stroke >/=70 years of age. Cognitive performance was determined with the use of a computerized assessment battery in 107 untreated hypertensives (55 women, age 76+/-4 years, blood pressure, 164+/-9/89+/-7; range, 138 to 179/68 to 99 mm Hg) and 116 normotensives (51 female, age 76+/-4 years, 131+/-10/74+/-7; 108 to 149/60 to 89 mm Hg). Older subjects with hypertension were significantly slower in all tests (reaction time, milliseconds; simple, 346+/-100 versus 318+/-56, P<0.05; memory scanning, 867+/-243 versus 789+/-159, P<0.01; immediate word recognition, 947+/-261 versus 886+/-192, P<0.05; and delayed word recognition, 937+/-230 versus 856+/-184, P<0.05; picture recognition, 952+/-184 versus 894+/-137, P<0.01; spatial memory, 1390+/-439 versus 1258+/-394, P<0.01; excepting choice reaction time, 510+/-75 versus 498+/-72, P=0.08). Accuracy was also impaired in tests of number vigilance, 99.2+/-2.5% versus 99.9+/-0.9, P<0.01; delayed word recognition, 83.5+/-16 versus 87.9+/-9.8, P<0.01; and spatial memory 64+/-32 versus 79+/-20, P<0.001. Hypertension in older subjects is associated with impaired cognition in a broad range of areas in the absence of clinically evident target organ damage.

Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects.

OBJECTIVE: To determine the potential role of whole brain atrophy, hippocampal atrophy, or both, and small vessel disease/white matter lesions as mechanisms underlying the cognitive impairment associated with hypertension. METHODS: Using MRI scanning the authors determined hippocampal volumes, whole brain volumes, and location and severity of white matter lesions, using Scheltens scale, in 103 hypertensive (166 +/- 8/88 +/- 7 mm Hg, 54 female) and 51 normotensive (132 +/- 12/74 +/- 7 mm Hg, 21 female) subjects age > or = 70 years. RESULTS: Compared to normotensive subjects, older hypertensive subjects had significantly smaller whole brain volumes (887 +/- 109 vs 930 +/- 97 cm3, p = 0.02) and nonsignificantly reduced hippocampal volumes (5.39 +/- 1.60 vs 5.67 +/- 1.80 cm3, p = 0.33). Hypertensive subjects had an increased burden of periventricular lesions: bands (p = 0.03), frontal caps (p = 0.08), occipital caps (p = 0.07), and total periventricular hyperintensities (p = 0.02). They also had higher scores in subcortical areas: frontal (p = 0.04), temporal (p = 0.03), and deep white matter areas (p = 0.05). A correlation was found between whole brain volumes and systolic blood pressure (r = -0.19, p = 0.02). No correlation was seen between whole brain volumes and white matter lesion burden. CONCLUSIONS: Moderate hypertension in non-impaired older subjects is associated with smaller whole brain volume and an increased burden of subcortical and periventricular white matter lesions.