Recognition of cognitive dysfunction in hospitalised older patients: a flash mob study.

BACKGROUND: It is important that healthcare professionals recognise cognitive dysfunction in hospitalised older patients in order to address associated care needs, such as enhanced involvement of relatives and extra cognitive and functional support. However, studies analysing medical records suggest that healthcare professionals have low awareness of cognitive dysfunction in hospitalised older patients. In this study, we investigated the prevalence of cognitive dysfunction in hospitalised older patients, the percentage of patients in which cognitive dysfunction was recognised by healthcare professionals, and which variables were associated with recognition. METHODS: A multicentre, nationwide, cross-sectional observational study was conducted on a single day using a flash mob study design in thirteen university and general hospitals in the Netherlands. Cognitive function was assessed in hospitalised patients aged ≥ 65 years old, who were admitted to medical and surgical wards. A Mini-Cog score of < 3 out of 5 indicated cognitive dysfunction. The attending nurses and physicians were asked whether they suspected cognitive dysfunction in their patient. Variables associated with recognition of cognitive dysfunction were assessed using multilevel and multivariable logistic regression analyses. RESULTS: 347 of 757 enrolled patients (46%) showed cognitive dysfunction. Cognitive dysfunction was recognised by attending nurses in 137 of 323 patients (42%) and by physicians in 156 patients (48%). In 135 patients (42%), cognitive dysfunction was not recognised by either the attending nurse or physician. Recognition of cognitive dysfunction was better at a lower Mini-Cog score, with the best recognition in patients with the lowest scores. Patients with a Mini-Cog score < 3 were best recognised in the geriatric department (69% by nurses and 72% by physicians). CONCLUSION: Cognitive dysfunction is common in hospitalised older patients and is poorly recognised by healthcare professionals. This study highlights the need to improve recognition of cognitive dysfunction in hospitalised older patients, particularly in individuals with less apparent cognitive dysfunction. The high proportion of older patients with cognitive dysfunction suggests that it may be beneficial to provide care tailored to cognitive dysfunction for all hospitalised older patients.

Lower blood pressure associated with higher mortality in elderly diabetic patients (ZODIAC-12).

OBJECTIVE: to investigate the relationship between blood pressure over time and mortality in elderly patients with type 2 diabetes mellitus (T2DM). DESIGN: prospective observational cohort study. SETTING: primary care, Zwolle, The Netherlands. SUBJECTS: patients with T2DM aged 60 years and older (n = 881). The cohort was divided into two age categories: 60-75 years and older than 75 years. METHODS: updated means for systolic, diastolic and pulse pressures were calculated after a median follow-up time of 9.8 years. These values were used as time-dependent covariates in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular mortality. RESULTS: all of the blood pressure measures were inversely related to all-cause mortality in elderly diabetic patients (>75 years). Furthermore, these relationships were specifically found in elderly patients treated with antihypertensive medication at baseline. A decrease of 10 mm Hg in systolic blood pressure, diastolic blood pressure and pulse pressure led to a mortality increase of 22% [95% confidence interval (95% CI): 13-31%], 30% [95% CI: 13%-46%] and 22% [95% CI: 11%-33%], respectively. In the low age group (60-75 years), no relationship was found between blood pressure and mortality. CONCLUSIONS: blood pressure is a marker for mortality in elderly T2DM patients; however, the relationship is inverse.

Are the orthostatic fluid shifts to the calves augmented in autonomic failure?

BACKGROUND: In autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are contradictory. METHODS: We evaluated pooling using strain-gauge plethysmography (SGP) during head-up tilt (HUT) with a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs and thus to maximise pooling. 23 healthy subjects and 12 patients with AF were tilted for 5 min. BP and calf volume changes, as measured by SGP, were measured continuously. Multiple regression analysis was used to examine the effect of AF on orthostatic fluid shifts after adjustment for potential confounders. RESULTS: Patients did not differ from controls with respect to the increase of calf volume after 5 min HUT. The acute (0-1 min) and the prolonged (1-5 min) phases of calf volume responses to HUT were also similar between patients and controls. No correlation was found between the degree of orthostatic hypotension and the orthostatic calf volume change in AF. In one patient an additional measurement was made before rising from bed in the early morning demonstrating a greater albeit small increase of calf volume upon HUT. CONCLUSION: Orthostatic fluid shifts at the level of the calf in AF are not augmented during the course of the day despite marked hypotension. However, a small increase of pooling may be expected when the patient first gets out of bed in the morning probably due to the absence of oedema.

C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

BACKGROUND: The role of C-reactive protein (CRP) in predicting vascular events and response to statin therapy remains uncertain. Additional large prospective studies are required. METHODS AND RESULTS: Baseline CRP was related to risk over 3.2 years for primary a combined end point (definite or suspected death from coronary heart disease, nonfatal myocardial infarction, and fatal or nonfatal stroke; n=865 events) and secondary (coronary heart disease events or stroke alone) and tertiary (stroke plus transient ischemic attack) end points in the Prospective Study of Pravastatin in the Elderly at Risk (n=5804 men and women; age, 70 to 82 years). CRP levels were higher in subjects who had a subsequent primary end-point event compared with those who did not (geometric mean; 3.64 mg/L [SD, 3.08 mg/L] versus 3.01 mg/L [SD, 3.05 mg/L]; P<0.0001). CRP correlated positively with body mass index and smoking status and negatively with high-density lipoprotein cholesterol. The unadjusted hazard ratio for the primary end point was 1.48 (95% CI, 1.26 to 1.74) in a comparison of top and bottom thirds for CRP, falling to 1.36 (95% CI, 1.15 to 1.61) with adjustment for established predictors and body mass index. Similar results were obtained for other end points or when results were examined separately by history of vascular disease. However, baseline CRP added minimally to risk prediction beyond conventional predictors and did not relate to the magnitude of pravastatin benefit. CONCLUSIONS: Elevated CRP minimally enhances cardiovascular disease prediction beyond established vascular risk factors and does not predict response to statin therapy in elderly subjects at risk. These data suggest that CRP has limited clinical value in cardiovascular disease risk stratification or predicting response to statin therapy in elderly people.

Diagnosing orthostatic hypotension with continuous and interval blood pressure measurement devices.

Orthostatic hypotension (OH) is defined as a drop in systolic blood pressure (SBP) of ≥20 mm Hg and/or a drop in diastolic blood pressure (DBP) of ≥10 mm Hg within 3 min of standing. The international guidelines recommend ideally diagnosing OH with a continuous blood pressure (BP) measurement device, although in daily practice interval BP measurement devices are used more often. We aimed to investigate the difference in observed prevalence of OH between an interval and a continuous BP measurement device. A total of 104 patients with a mean age of 69 years were included. The prevalence of OH was 35.6% (95% CI: 26.4-44.8) with the interval BP measurement and 45.2% (95% CI: 35.6-54.8) with the continuous BP measurement device (P = .121). Lin's coefficient of concordance ranged from 0.47 to 0.59 for the drop in systolic blood pressure and from 0.33 to 0.42 for the drop in diastolic blood pressure. The positive proportion of agreement in diagnosis of OH between the interval and continuous measure was 59.5% and the negative proportion of agreement was 72.5%. Although the prevalence of OH was not significantly different between the continuous and the interval BP measurement devices using a similar amount of measurement, the concordance between interval and continuous measure is low resulting in low positive and negative proportions of agreement in the diagnosis of OH. We conclude that continuous BP measurement cannot be substituted by an interval BP measurement to diagnose OH.

Assessment of orthostatic fluid shifts with strain gauge plethysmography.

We evaluated the use of strain gauge plethysmography (SGP) for the assessment of orthostatic fluid shifts during head up tilt (HUT). Subjects wore a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs during HUT. 22 Healthy subjects (9 women) were tilted for 5 minutes. Calf volume changes as measured by SGP, surface EMG, heart rate and blood pressure were measured continuously. Ten subjects underwent a second tilt test during which circulation in one leg was occluded with a pressure cuff at 250 mmHg. During HUT with occlusion, calf volume increased in the non-occluded leg by 1.9+/-0.3% (mean +/- SEM) and 0.2+/-0.2% in the occluded leg (p<0.001). During HUT without occlusion a significant correlation (r = 0.9) was found between measurements of the left and right leg with a mean difference of 0.03+/-0.1%. HUT did not cause significant changes of surface EMG. An unexpected gender effect was found: calf volume increased significantly more in men than in women. Men were significantly taller, but the hemodynamic response to HUT did not differ between both sexes. The gender effect on orthostatic increases of calf volume remained significant after adjustment for heart-to-calf distance. SGP during HUT with a parachute harness is a new, promising method to assess orthostatic fluid shifts. The gender differences in orthostatic pooling in the calf may be explained by a higher calf compliance in men together with a greater hydrostatic pressure due to a greater height in men.

Standing orthostatic blood pressure measurements cannot be replaced by sitting measurements.

As many elderly patients are not able to stand for several minutes, sitting orthostatic blood pressure (BP) measurements are sometimes used as an alternative. We aimed to investigate the difference in BP response and orthostatic hypotension (OH) prevalence between the standard postural change to the sitting and the standing position in a cross-sectional observational study. BP was measured with a continuous BP measurement device during two postural changes, from supine to the sitting and from supine to the standing position. Linear mixed models were used to investigate the differences in changes (Δ) of systolic BP (SBP) and diastolic BP (DBP) between the two postural changes. The prevalence and the positive and negative proportions of agreement of OH were calculated of the two postural changes. One hundred and four patients with a mean age of 69 years were included. ΔSBP was significantly larger in the standing position compared with the sitting between 0 and 44 s. ΔDBP was significantly larger in the sitting position compared with the standing 75-224 s after postural change. The prevalence of OH was 66.3% (95% confidence interval (CI) 57.2, 75.4) in the standing position and 67.3% (95% CI 58.3, 76.3) in the sitting position. The positive proportion of agreement was 74.8% and the negative proportion of agreement was 49.3%. A clear difference was seen in BP response between the two postural changes. Although no significant difference in prevalence of OH was observed, the positive and negative proportion of agreement of the prevalence of OH were poor to moderate, which indicates a different outcome between both postural changes.

Recognition of Delirium in Postoperative Elderly Patients: A Multicenter Study.

OBJECTIVES: To evaluate to what extent delirium experts agree on the diagnosis of delirium when independently assessing exactly the same information and to evaluate the sensitivity of delirium screening tools in routine daily practice of clinical nurses. DESIGN: Prospective observational longitudinal study. SETTING: Three medical centers in the Netherlands. PARTICIPANTS: Elderly postoperative adults (n = 167). MEASUREMENTS: A researcher examined participants daily (Postoperative Day 1-3) for delirium using a standardized cognitive assessment and interview including the Delirium Rating Scale Revised-98 as global impression without any cut-off values that was recorded on video. Two delirium experts independently evaluated the videos and clinical information from the last 24 hours in the participants' record and classified each assessment as delirious, possibly delirious, or not delirious. Interrater agreement between the delirium experts was determined using weighted Cohen's kappa. When there was no consensus, a third expert was consulted. Final classification was based on median score and compared with the results of the Confusion Assessment Method for Intensive Care Unit and Delirium Observation Scale that clinical nurses administered. RESULTS: Four hundred twenty-four postoperative assessments of 167 participants were included. The overall kappa was 0.61 (95% confidence interval = 0.53-0.68). There was no agreement between the experts for 89 (21.0%) assessments and a third delirium expert was needed for the final classification. Delirium screening that nurses performed detected 32% of the assessments that the experts diagnosed as (possibly) delirious. CONCLUSION: There was considerable disagreement in classification of delirium by experts who independently assessed exactly the same information, showing the difficulty of delirium diagnosis. Furthermore, the sensitivity of daily delirium screening by clinical nurses was poor. Future research should focus on development of objective instruments to diagnose delirium.

Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

BACKGROUND: Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHOD AND RESULTS: The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group (P=0.27), nor did on-treatment LDLc in the pravastatin group (P=0.12). HDLc was inversely associated with risk in subjects on placebo (P=0.0019) but not in those on pravastatin (P=0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc (P=0.38) but exhibited a significant interaction with HDLc (P=0.012). Subjects in the lowest 2 quintiles of HDLc (<1.15 mmol/L) had a risk reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81; P<0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95% confidence limits, 0.88, 1.27; P=0.53). During follow-up, there was no relation between achieved level of LDLc or HDLc and risk. However, the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy. CONCLUSIONS: In people >70 years old, HDLc appears to be a key predictor of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc <1.15 mmol/L or an LDLc/HDLc ratio >3.3.

Endothelium-dependent NO-mediated vasodilation in humans is attenuated by peripheral alpa1-adrenoceptor activation.

OBJECTIVES: The release of nitric oxide is controlled by cholinergic and adrenergic receptors. Recent observations suggest that activation of alpha-adrenoceptors can inhibit the release of nitric oxide. The aim of the present study was to examine the effect of alpha1- and alpha2-adrenoceptor activation on nitric oxide-mediated vasodilation. METHODOLOGY: In a first set of experiments, the endothelium-dependent vasodilators acetylcholine (ACh), 5-hydroxytryptamine (5HT), and bradykinin (BK), and the nitric oxide donor sodium nitroprusside (SNP) were administered in a random order in the brachial artery together with saline, or the nonselective alpha-adrenoceptor agonists norepinephrine or clonidine, or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). The infusions of saline, norepinephrine, clonidine, and L-NMMA started 10 minutes before the infusions of ACh, BK, 5HT, and SNP. In a second set of experiments, cumulative doses of ACh, BK, and 5HT were infused, in a random order, intra-arterially together with saline or the selective alpha1-adrenoceptor agonist methoxamine. The infusions of saline and methoxamine started 5 minutes before the infusions of ACh, BK, and 5HT. Forearm blood flow was measured using computerized venous occlusion plethysmography. RESULTS: ACh, 5HT, BK, and SNP induced a significant increase in forearm blood flow (p < 0.05 for all). These vasodilator responses were significantly attenuated by norepinephrine, clonidine, and L-NMMA (p <0.05 for all), except for SNP. In the second set of experiments, all three endothelium-dependent vasodilators induced a dose-dependent vasodilation, which was significantly inhibited by methoxamine (p <0.05). CONCLUSION: These results show that endothelium-dependent nitric oxide-mediated vasodilation is inhibited by activation of peripheral alpha1-adrenoceptors.

Basal cerebral blood flow is dependent on the nitric oxide pathway in elderly but not in young healthy men.

OBJECTIVE: Brain perfusion is tightly regulated over a wide range of blood pressures by local regulation of cerebral blood flow (CBF). Ageing is associated with impaired CBF and impaired nitric oxide mediated vasodilator responses. The role of nitric oxide in the regulation of basal CBF in young and older subjects was investigated, using the nitric oxide synthase inhibitor L-NMMA as pharmacological tool. METHODS: We used a gradient echo phase-contrast magnetic resonance imaging technique to investigate the role of nitric oxide in the regulation of cerebral blood flow in young (25+/-7.1 years; n=8) and old (78+/-6.6 years; n=7) volunteers. The study was performed in a double-blinded fashion and consisted of two study days. On one day the effects of the intravenously infused L-NMMA on CBF and blood pressure was measured and on the other day the effects of a matching placebo. RESULTS: Basal CBF was significantly lower in old compared to young subjects (590+/-20 vs 704+/-20 ml/min), while the cerebral vascular resistance (CVR) levels were significantly higher (0.15+/-0.01 (arbitrary units) vs 0.12+/-0.01, respectively). Infusion of L-NMMA significantly increased mean arterial pressure in both groups (2.8+/-1.2 mmHg; p=0.02 in the young and in the old subjects 5.6+/-1.1 mmHg; p<0.001). Infusion of L-NMMA significantly decreased CBF (49+/-12 ml/min; p<0.001) and increased CVR (0.02+/-0.004; p<0.001) in the old subjects but did not significantly influence cerebral circulation in the young subjects. CONCLUSION: We conclude that compared to young subjects, in old people CBF is impaired, and dependent on the intactness of the nitric oxide pathway.

Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study.

BACKGROUND: Although orthostatic hypotension (OH) is more prevalent in old age, and in patients with diabetes, the prevalence of OH in older patients with type 2 diabetes mellitus is unknown. AIM: To establish the prevalence of OH, and its association with falling, in home-dwelling older participants with and without type 2 diabetes. DESIGN AND SETTING: A cross-sectional study in primary care in the Netherlands. METHOD: A total of 352 patients with type 2 diabetes, and 211 without participated in this study. OH was defined as a fall in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic after either 1 or 3 minutes in an upright position. Feelings of dizziness, light-headedness, or faintness during the standing period were documented as orthostatic complaints. Fall risk was assessed with a validated risk profile instrument. RESULTS: The prevalence of OH was 28% (95% CI = 24% to 33%) and 18% (95% CI = 13% to 23%) in participants with and without type 2 diabetes, respectively. OH was not related to falling, while the presence of orthostatic complaints in itself was associated with both previous fall incidents as well as a high fall risk, even after adjustment for OH. The adjusted odds ratios were 1.65 (95% CI = 1.00 to 2.72) and 8.21 (95% CI = 4.17 to 16.19), respectively. CONCLUSION: OH is highly prevalent in home-dwelling older people with and without type 2 diabetes. Those with orthostatic complaints had an increased risk for falling, whereas those with OH were not.

Severe gastroenteritis as presentation of a primary cytomegalovirus infection in an immunocompetent woman.

In immunocompetent hosts, symptomatic cytomegalovirus (CMV) infection occurs in around 10% and has traditionally been considered to have a benign, self-limiting course. Active CMV infection in immunocompetent subjects is very rare. However, manifestations of CMV infection in immunocompromised hosts have been extensively reported. We present a case of a 58-year-old immunocompetent woman with a primary cytomegalovirus infection which presented as a severe gastroenteritis and hepatitis.

The lipid profile and mortality risk in elderly type 2 diabetic patients: a ten-year follow-up study (ZODIAC-13).

BACKGROUND: The precise relationship between the lipid profile and mortality in elderly patients with type 2 diabetes mellitus (T2DM) remains unclear. The aim of this study was to investigate the relationship between the lipid profile over time, and mortality in elderly patients with T2DM. METHODS AND FINDINGS: In 1998, 881 primary care patients with T2DM aged 60 years and older participated in the ZODIAC study, a prospective observational study. The cohort was divided into two age categories: 60-75 years and older than 75 years. Updated means of all lipid profile indices were calculated after a median follow-up time of 9.8 years. These values were used as time dependent covariates in a Cox proportional hazard model. The cholesterol-HDL ratio and LDL-cholesterol were positively related to both all-cause and cardiovascular mortality in the low age group. In contrast, except for the triglyceride level, none of the other lipid profile indices were related to all-cause mortality in patients aged over 75 years. The mortality risk decreased by 17% (95%CI: 5% to 27%) for each 1 mmol/L higher serum level of triglycerides. The relationships between the various lipid profile indices and cardiovascular mortality were not significant. However, the results were different after stratification for diabetes duration. In the subgroup of elderly patients with a diabetes duration of 8 years and longer, higher lipids were predictive of increased cardiovascular mortality. The main limitation of this study is its observational design, which prevents us drawing conclusions about causality. CONCLUSION: Although the lipid profile was not predictive in the overall group of elderly patients, higher lipids were related to increased cardiovascular mortality in patients with diabetes of long duration. In order to make valid recommendations concerning lipid-lowering treatment, a randomized controlled trial or a meta-analysis concerning this specific population is mandatory.

Use of calcium antagonists and cognitive decline in old age. The Leiden 85-plus study.

The systolic hypertension in Europe (Syst-Eur) trial has been the only trial that has suggested a protective effect of antihypertensive treatment on incidence of dementia. It is unclear whether this protective effect has been caused by the blood pressure lowering effect of the calcium antagonist nitrendipine or by the calcium channel inhibition. From the Leiden 85-plus study, a population-based cohort study of 599 subjects aged 85 years, we selected 204 subjects who used at least one antihypertensive at baseline. Associations between use of antihypertensives at baseline and change in cognitive functioning over time were assessed with linear mixed models. After adjusting for gender, education, and use of other antihypertensives, only use of calcium antagonists was associated with a significant decelerated annual cognitive decline during follow-up (0.40 MMSE-points per year, p=0.001). Use of other antihypertensives was not associated with a decelerated annual cognitive decline (all p values >0.3). Our data support the interpretation that the reported prevention of dementia by calcium antagonists is exerted through its calcium channel inhibition rather than its blood pressure lowering properties.

Serum calcium and cognitive function in old age.

OBJECTIVES: To determine whether serum calcium is associated with cognitive function in elderly individuals in the general population. DESIGN: Prospective follow-up study of two independent, population-based cohorts. SETTING: The Rotterdam Study (median follow-up 11 years) and the Leiden 85-plus Study (median follow-up 5 years). PARTICIPANTS: Three thousand nine hundred ninety-four individuals, mean age 71, from the Rotterdam Study and 560 individuals, all aged 85, from the Leiden 85-plus Study. MEASUREMENTS: Global cognitive function was assessed in both cohorts using the Mini-Mental State Examination; attention, psychomotor speed, and memory function were assessed in the Leiden 85-plus Study only. Linear regression and linear mixed models were used for statistical analyses. RESULTS: In the Rotterdam Study, high serum calcium was associated with worse global cognitive function at baseline (P<.05) and a faster rate of decline in cognitive function during follow-up (P=.005) in individuals aged 75 and older but not in younger individuals. In the Leiden 85-plus Study, high serum calcium was associated with worse global cognitive function from age 85 through 90 (P<.001). This observation also held for the specific cognitive domains tested (all P<.01). These results did not change when individuals with serum calcium levels greater than normal (>2.55 mmol/L) were excluded from the analyses. CONCLUSION: In the general population, high serum calcium levels are associated with faster decline in cognitive function over the age of 75.

Association between apolipoprotein E4 and cognitive decline in elderly adults.

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E(4) versus those without E(4) had poorer memory performance (mean score difference -0.20 (95% confidence interval (CI)=-0.31 to -0.09) for immediate recall and -0.32 (95% CI=-0.48 to -0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20-4.28); Letter-Digit score, -0.36, (95% CI=-0.77-0.05). Subjects with apolipoprotein E(4) showed a greater decline in immediate (-0.22, 95% CI=-0.33 to -0.11) and delayed (-0.30, 95% CI=-0.46 to -0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter-Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E(4), 4.3% in E(4) heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E(4)) and 8.9% to 13.8% in E(4) homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E(4) was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E(4) is associated with more-rapid cognitive decline and may, therefore, predispose to dementia.

Predictors of functional decline in elderly people with vascular risk factors or disease.

OBJECTIVE: to determine contributors to decline in functional capacity in elderly patients with known vascular risk factors or disease. DESIGN: secondary analysis of longitudinal data gathered over an average 3.2 years of follow-up. PARTICIPANTS: 5,804 community-dwelling subjects aged 70-82 years with a history of, or risk factors for, ischaemic vascular disease. MEASUREMENTS: basic activities of daily living were measured serially through the study using the 20-point Barthel index and extended activities using a 14-point Instrumental Activities of Daily Living (IADL). RESULTS: over the period of study 896/5,661 (16%) subjects had deterioration in Barthel (mean reduction 0.35, SD 1.76) and 1,270/5,662 (22%) had a reduction in IADL score (mean 0.63, SD 2.15). Independent risk factors at baseline for a reduction in Barthel and IADL were age, female gender and diabetes mellitus. A history of vascular disease and smoking were also significant predictors of reduction in IADL. The development of a new cerebrovascular event was associated with a greatly increased risk of reduction in the Barthel and IADL score (multivariate OR 3.71 (95% CI 2.94, 4.69) and 3.71 (95% CI 2.96, 4.66), respectively). A similar pattern was seen for non-fatal myocardial infarction. Incident cerebrovascular events and non-fatal myocardial infarction accounted for 31 and 11%, respectively, of the population decline in Barthel, and 24 and 10% of the decline in IADL. CONCLUSION: incident vascular events were important contributors to functional decline in this population, accounting for almost half of the observed deterioration in basic activities of daily living and approximately one-third of the reduction in IADL. Prevention of ischaemic vascular events over the short to medium term should reduce the burden of disability in high-risk older subjects.