The clock drawing test, mortality, incident cardiovascular events and dementia.

OBJECTIVE: The purpose of this study is to examine the association of the clock drawing test (CDT) with incident dementia, cardiovascular events and mortality in very elderly hypertensive patients. METHOD: All participants were hypertensive and aged 80 years and over. The CDT was administered at baseline and annually thereafter. Data on incident cardiovascular, fatal events and dementia were collected over follow-up. RESULTS: There were 3845 participants recruited and followed up for a mean of 2.1 years. Of these, 2701 completed a CDT with 2259 available at baseline. Of this group, 6.6% had a cardiovascular event, 6.1% died, and 10% were diagnosed with dementia. There was no relationship between baseline CDT score and subsequent cardiovascular events or mortality. For incident dementia, the hazard ratio was 0.88 (95% confidence intervals 0.83-0.94) suggesting that better performance on the baseline CDT was associated with a lower risk of dementia. CONCLUSION: These results provide tentative support for the CDT alongside other cognitive screening tools in a hypertensive elderly population.

Kidney function in the very elderly with hypertension: data from the hypertension in the very elderly (HYVET) trial.

BACKGROUND: numerous reports have linked impaired kidney function to a higher risk of cardiovascular events and mortality. There are relatively few data relating to kidney function in the very elderly. METHODS: the Hypertension in the Very Elderly Trial (HYVET) was a randomised placebo-controlled trial of indapamide slow release 1.5mg ± perindopril 2-4 mg in those aged ≥80 years with sitting systolic blood pressures of ≥160 mmHg and diastolic pressures of <110 mmHg. Kidney function was a secondary outcome. RESULTS: HYVET recruited 3,845 participants. The mean baseline estimated glomerular filtration rate (eGFR) was 61.7 ml/min/1.73 m(2). When categories of the eGFR were examined, there was a possible U-shaped relationship between eGFR, total mortality, cardiovascular mortality and events. The nadir of the U was the eGFR category ≥60 and <75 ml/min/1.73 m(2). Using this as a comparator, the U shape was clearest for cardiovascular mortality with the eGFR <45 ml/min/1.73 m(2) and ≥75 ml/min/1.73 m(2) showing hazard ratios of 1.88 (95% CI: 1.2-2.96) and 1.36 (0.94-1.98) by comparison. Proteinuria at baseline was also associated with an increased risk of later heart failure events and mortality. CONCLUSIONS: although these results should be interpreted with caution, it may be that in very elderly individuals with hypertension both low and high eGFR indicate increased risk.

Sociodemographic and lifestyle risk factors for incident dementia and cognitive decline in the HYVET.

INTRODUCTION: previous studies have suggested that smoking, living alone and having a high body mass index may increase risk of developing dementia whereas a normal body mass index, having received education and moderate alcohol consumption may decrease risk. Dementia risk also increases with age and is thought to be higher in hypertensives. METHOD: we used data collected in the Hypertension in the Very Elderly Trial (HYVET), and cognitive function was assessed using the Mini-Mental State Examination (MMSE) at baseline and annually. Participants with a fall in MMSE to <24 or with a fall of 3 points in any 1 year were investigated further. The association of baseline sociodemographic, medical and lifestyle factors with incident dementia or decline in MMSE scores was assessed by regression models. RESULTS: incident dementia occurred in 263 of 3,336 participants over a mean follow-up of 2 years. In multivariate analyses, being underweight, BMI < 18.5 (HR 1.90, 95% CI 1.06-3.39) or obese, BMI >30 (HR 1.84, 95% CI 1.24-2.72), increased risk of incident dementia as did piracetam use (HR 2.72, 95% CI 1.60-4.63). Receiving formal education was associated with a reduced risk (HR 0.59, 95% CI 0.45-0.78). There was no association with smoking, alcohol and gender. Similar results were found when examining mean annual change in the MMSE score. DISCUSSION: our results for BMI and education agree with those from other studies. The increased risk associated with piracetam may reflect awareness of memory problems before any diagnosis of dementia has been made. Trial participants may be healthier than the general population and further studies in the general population are required.

Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial.

BACKGROUND: Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia; however, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence. The Hypertension in the Very Elderly trial (HYVET) was designed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function. METHODS: Patients with hypertension (systolic pressure 160-200 mm Hg; diastolic pressure <110 mm Hg) who were aged 80 years or older were enrolled in this double-blind, placebo-controlled trial. Participants were randomly assigned to receive 1.5 mg slow release indapamide, with the option of 2-4 mg perindopril, or placebo. The target systolic blood pressure was 150 mm Hg; the target diastolic blood pressure was 80 mm Hg. Participants had no clinical diagnosis of dementia at baseline, and cognitive function was assessed at baseline and annually with the mini-mental state examination (MMSE). Possible cases of incident dementia (a fall in the MMSE score to <24 points or a drop of three points in 1 year) were assessed by standard diagnostic criteria and expert review. The trial was stopped in 2007 at the second interim analysis after treatment resulted in a reduction in stroke and total mortality. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00122811. FINDINGS: 3336 HYVET participants had at least one follow-up assessment (mean 2.2 years) and were included: 1687 participants were randomly assigned to the treatment group and 1649 to the placebo group. Only five reports of adverse effects were attributed to the medication: three in the placebo group and two in the treatment group. The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg, p<0.0001; and diastolic -5.9 mm Hg, p<0.0001. There were 263 incident cases of dementia. The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group. There was no significant difference between treatment and placebo groups (hazard ratio [HR] 0.86, 95% CI 0.67-1.09); however, when these data were combined in a meta-analysis with other placebo-controlled trials of antihypertensive treatment, the combined risk ratio favoured treatment (HR 0.87, 0.76-1.00, p=0.045). INTERPRETATION: Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up, owing to the early termination of the trial, or the modest effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia.

Haemoglobin, anaemia, dementia and cognitive decline in the elderly, a systematic review.

BACKGROUND: Anaemia may increase risk of dementia or cognitive decline. There is also evidence that high haemoglobin levels increase risk of stroke, and consequently possible cognitive impairment. The elderly are more at risk of developing dementia and are also more likely to suffer from anaemia, although there is relatively little longitudinal literature addressing this association. METHODS: To evaluate the evidence for any relationship between incident cognitive decline or dementia in the elderly and anaemia or haemoglobin level, we conducted a systematic review and meta-analyses of peer reviewed publications. Medline, Embase and PsychInfo were searched for English language publications between 1996 and 2006. Criteria for inclusion were longitudinal studies of subjects aged > or =65, with primary outcomes of incident dementia or cognitive decline. Other designs were excluded. RESULTS: Three papers were identified and only two were able to be combined into a meta-analysis. The pooled hazard ratio for these two studies was 1.94 (95 percent confidence intervals of 1.32-2.87) showing a significantly increased risk of incident dementia with anaemia. It was not possible to investigate the effect of higher levels of haemoglobin. CONCLUSION: Anaemia is one factor to bear in mind when evaluating risk of incident dementia. However, there are few data available and the studies were methodologically varied so a cautionary note needs to be sounded and our primary recommendation is that further robust research be carried out.

Smoking, dementia and cognitive decline in the elderly, a systematic review.

BACKGROUND: Nicotine may aid reaction time, learning and memory, but smoking increases cardiovascular risk. Cardiovascular risk factors have been linked to increased risk of dementia. A previous meta-analysis found that current smokers were at higher risk of subsequent dementia, Alzheimer's disease, vascular dementia and cognitive decline. METHODS: In order to update and examine this further a systematic review and meta-analysis was carried out using different search and inclusion criteria, database selection and more recent publications. Both reviews were restricted to those aged 65 and over. RESULTS: The review reported here found a significantly increased risk of Alzheimer's disease with current smoking and a likely but not significantly increased risk of vascular dementia, dementia unspecified and cognitive decline. Neither review found clear relationships with former smoking. CONCLUSION: Current smoking increases risk of Alzheimer's disease and may increase risk of other dementias. This reinforces need for smoking cessation, particularly aged 65 and over. Nicotine alone needs further investigation.

Cardiovascular and biochemical risk factors for incident dementia in the Hypertension in the Very Elderly Trial.

OBJECTIVES: Several cardiovascular and biochemical factors including hypertension have been associated with cognitive decline and dementia, although both epidemiological and intervention evidence is mixed with the majority of studies examining those in midlife or younger elderly and the recent Hypertension in the Very Elderly Trial showing no significant association between blood pressure lowering and incident dementia. It has also been suggested that risk factors may differ in the very elderly. The aim of these analyses was to examine the impact of baseline cardiovascular and biochemical factors upon incident dementia and cognitive decline in a very elderly hypertensive group. METHODS: Participants of the Hypertension in the Very Elderly Trial were aged at least 80 years and hypertensive. Cognitive function was assessed at baseline and annually with diagnostic information collected for dementia and relationships between baseline total and high-density lipoprotein cholesterol, creatinine, glucose, haemoglobin, heart failure, atrial fibrillation, diabetes, previous stroke and later dementia/cognitive decline were examined. RESULTS: There were 3336 participants with longitudinal cognitive function data. In multivariate analyses higher creatinine was associated with a lower risk of incident dementia and cognitive decline. Higher total and lower high-density lipoprotein cholesterol were associated with lower risk of cognitive decline. Other variables were not significant. CONCLUSIONS: In very elderly hypertensive patients heart failure, diabetes, atrial fibrillation, prior stroke, glucose and haemoglobin levels did not demonstrate a relationship with cognitive decline or dementia. Higher creatinine (excluding moderate renal impairment) was associated with a lower risk of dementia and cognitive decline. The findings for total and high-density lipoprotein cholesterol add to the varied literature in this area and together these findings may add weight to the suggestion that risk factor profiles differ in the very elderly.

Vascular risk factors and cognitive function among 3763 participants in the Hypertension in the Very Elderly Trial (HYVET): a cross-sectional analysis.

BACKGROUND: It is well known that the global population is aging and that those over the age of 80 are the fastest growing part of this expansion. Also known is that prevalence of hypertension and cognitive decline both increase with increasing age. METHOD: The Hypertension in the Very Elderly Trial (HYVET) was a double blind placebo-controlled trial of antihypertensive treatment (indapamide SR 1.5 mg +/- perindopril 2-4 mg) and recruited only those hypertensives who were aged 80 or over and were without a diagnosis of dementia at baseline. Systolic blood pressure had to be in the range 160-199 mmHg and diastolic pressure <110 mmHg. Cognitive function was assessed at baseline using the Mini-mental State Examination prior to randomization into the trial. Also collected at baseline was information relating to sociodemographic, clinical, cardiovascular and biochemical factors which may impact upon cognitive function. This paper reports on the baseline cognitive function data from the HYVET trial and its relationship to these factors. RESULTS: The mean age of the 3763 HYVET participants who had full cognitive function data at baseline was 83.6 years; 60 percent were female. The median MMSE score at baseline was 26 and, in multivariate analyses, higher at younger age, with male gender, higher educational level, having higher creatinine, higher total cholesterol and lower high-density lipoprotein cholesterol. CONCLUSIONS: This is the first such study to examine a large number of very elderly hypertensives and it shows some similar patterns to those seen in younger elderly groups.