The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to ...identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT).
The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD (eGFR ≤20 ml/min/1.73 m
) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed.
The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all p-values < 0.003). A history of vascular disease (p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed.
Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.
Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications ...have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.
Low high‐density lipoprotein cholesterol is associated with an increased risk for cardiovascular disease and stroke. At the same time, cardiovascular disease and stroke are important risk factors for ...dementia. We assessed the association between total and fractionated cholesterol and cognitive impairment and explored whether observed associations were dependent on or independent of atherosclerotic disease. In a population‐based study, total cholesterol, triglycerides, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol were measured in 561 subjects 85 years old and grouped in three equal strata representing decreasing serum concentrations. History of cardiovascular disease and stroke was determined. All subjects completed the Mini‐Mental State Examination (MMSE), and the presence of dementia was determined. Median MMSE scores were significantly lower in subjects with low high‐density lipoprotein cholesterol (25 points vs 27 points, p < 0.001). No differences in MMSE scores were found for other lipids and lipoproteins. MMSE scores in subjects with and without cardiovascular disease were 26 and 27 points (p = 0.007), respectively, and in subjects with and without stroke were 21 and 26 points (p < 0.001), respectively. The associations between low MMSE scores and low high‐density lipoprotein cholesterol remained significant after subjects with cardiovascular disease or stroke were excluded. In a comparison of subjects with low high‐density lipoprotein cholesterol with subjects with high high‐density lipoprotein cholesterol, the odds ratio for dementia was 2.3 (95% confidence interval, 1.2–4.3), and in subjects without cardiovascular disease or stroke, it was 3.7 (95% confidence interval, 1.3–10.1). All odds ratios were unaffected by education, low‐density lipoprotein cholesterol, triglycerides, and survival. Low high‐density lipoprotein cholesterol is associated with cognitive impairment and dementia. At least part of the association between high‐density lipoprotein cholesterol and cognitive function is independent of atherosclerotic disease.
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).
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.
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.
Orthostatic hypotension (OH), a blood pressure drop after postural change, is associated with impaired standing balance and falls in older adults. This study aimed to assess the association between ...blood pressure (BP) and a measure of quality of standing balance, i.e. Center of Pressure (CoP) movement, after postural change from supine to standing position in geriatric outpatients, and to compare CoP movement between patients with and without OH.
In a random subgroup of 75 consecutive patients who were referred to a geriatric outpatient clinic, intermittent BP measurements were obtained simultaneously with CoP measurements in mediolateral and anterior-posterior direction directly after postural change during 3 min of quiet stance with eyes open on a force plate. Additional measurements of continuous BP were available in n = 38 patients. Associations between BP change during postural change and CoP movement were analyzed using Spearman correlation. Mann-Whitney-U tests were used to compare CoP movement between patients with OH and without OH, in which OH was defined as a BP drop exceeding 20 mmHg of systolic BP (SBP) and/or 10 mmHg of diastolic BP (DBP) within 3 min after postural change.
OH measured intermittently was found in 8 out of 75 (11%) and OH measured continuously in 22 out of 38 patients (57.9%). BP change did not associate with CoP movement. CoP movement did not differ significantly between patients with and without OH.
Results do not underpin the added value of CoP movement measurements in diagnosing OH in a clinical setting. Neither could we identify the role of CoP measurements in the understanding of the relation between OH and impaired standing balance.
Objective
Recently, the fat mass and obesity‐associated gene (FTO) has been identified as a genetic risk factor for developing obesity. The underlying mechanisms remain speculative. SNPs within FTO ...have been associated with brain atrophy in frontal and occipital regions, suggesting that FTO might affect body weight through cerebral pathways. Behavioral studies suggested a relationship between FTO and the reward‐related behavioral traits. Therefore the relationship between the FTO risk allele rs9939609A and volumes of reward‐related brain structures has been investigated.
Methods
Four hundred and ninety‐two Dutch individuals (56% males, age: 70‐82 years) participating in the PROSPER study underwent a 3D‐T1‐weighted MRI to assess the volumes of reward‐related brain structures (e.g., amygdala, nucleus accumbens) and of gray matter and white matter. Linear regression analysis was performed to test for the association of subcortical and cortical structures with rs9939609A.
Results
rs9939609A is associated with lower volumes of the nucleus accumbens (p=0.03) and trended toward lower cortical gray matter volumes (p=0.08). This association is independent of gender, age, and BMI, FDR corrected.
Conclusions
The FTO risk allele is associated with lower nucleus accumbens volumes, suggesting that the higher body weight of risk‐allele carriers might be due to changes within reward‐related brain structures.
Background. White blood cell (WBC) count is, like C-reactive protein (CRP), a clinical marker of inflammation and predicts cardiovascular disease and mortality in middle-aged populations. Limited ...data exist on the association between WBC count and mortality in the oldest old. Moreover, because CRP and WBC count are closely linked, it is not known whether WBC count and CRP are independent risk factors for mortality. We assessed the independent predictive value of WBC count and CRP levels in relation to mortality, both vascular and nonvascular, in very old participants. Methods. A total of 599 women and men were evaluated longitudinally in the Leiden 85-plus Study. Blood samples and medical information were collected at age 85, and all participants were visited annually until age 90 or death. Mortality risks were estimated with Cox proportional hazard models. Results. Increasing WBC count was associated with an increased risk for all-cause mortality (hazard ratio, HR 95% confidence interval, CI = 1.26 1.15–1.38) after adjustment for sex and smoking status. CRP levels were also associated with an increased risk for mortality (HR 95% CI = 1.22 1.10–1.35). The association between increasing WBC count and mortality remained significant after adjustment for CRP levels (HR 95% CI = 1.20 1.09–1.33), whereas also the relation between increasing CRP levels and mortality remained significant after adjustment for WBC count (HR 95% CI = 1.17 1.05–1.30). Conclusion. Our results suggest that WBC count and CRP levels both independently predict mortality in the oldest old.
OBJECTIVESSelf-rated health (SRH) is an important patient-reported outcome, but little is known about SRH after a visit to the emergency department (ED). We investigated the determinants of decline ...in SRH during 3 months after an ED visit in older patients.
DESIGNThis was a multicenter prospective cohort study including acutely presenting older ( ≥ 70 years) patients in the ED (the Netherlands). Patients were asked to self-rate their health between 0 and 10. The main outcome was a decline in SRH defined as a transition of a SRH of at least 6 to a SRH of less than 6, 3 months after the patient’s visit to the ED.
RESULTSThree months after the ED visit, 870 (71.4%) patients had a stable SRH and 209 (11.5%) patients declined in SRH. Independent predictors with a decline in SRH weremale gender (OR 1.83) living alone (OR 1.56), living in residential care or nursing home (OR 2.75), number of different medications (OR 1.08), using a walking device (OR 1.70), and the Katz-ADL score (OR 1.22). Patients with functional decline 3 months after an ED visit show a steeper decline in the mean SRH (0.68 points) than patients with no functional decline (0.12 points, P < 0.001).
CONCLUSIONDecline in SRH after an ED visit in older patients is at least partly dependent on factors of functional capacity and functional decline. Preventive interventions to maintain functional status may be the solution to maintain SRH, but more research is needed to further improve and firmly establish the clinical usability of these findings.
The impact of total serum cholesterol as a risk factor for cardiovascular disease decreases with age, which casts doubt on the necessity for cholesterol-lowering therapy in the elderly. We assessed ...the influence of total cholesterol concentrations on specific and all-cause mortality in people aged 85 years and over.
In 724 participants (median age 89 years), total cholesterol concentrations were measured and mortality risks calculated over 10 years of follow-up. Three categories of total cholesterol concentrations were defined: <5·0 mmol/L, 5·0–6·4 mmol/L, and ⩾6·5 mmol/L. In a subgroup of 137 participants, total cholesterol was measured again after 5 years of follow-up. Mortality risks for the three categories of total cholesterol concentrations were estimated with a Cox proportional-hazards model, adjusted for age, sex, and cardiovascular risk factors. The primary causes of death were coded according to the International Classification of Diseases (ICD-9).
During 10 years of follow-up from Dec 1, 1986, to Oct 1, 1996, a total of 642 participants died. Each 1 mmol/L increase in total cholesterol corresponded to a 15% decrease in mortality (risk ratio 0–85 95% Cl 0·79–0·91). This risk estimate was similar in the subgroup of participants who had stable cholesterol concentrations over a 5-year period. The main cause of death was cardiovascular disease with a similar mortality risk in the three total cholesterol categories. Mortality from cancer and infection was significantly lower among the participants in the highest total cholesterol category than in the other categories, which largely explained the lower all-cause mortality in this category.
In people older than 85 years, high total cholesterol concentrations are associated with longevity owing to lower mortality from cancer and infection. The effects of cholesterol-lowering therapy have yet to be assessed.
Statin therapy has been found to substantially and significantly reduce coronary events in carriers of the KIF6 719Arg variant (rs20455) but not in noncarriers. We investigated whether, among the ...elderly, statin therapy also significantly reduced coronary events in carriers but not in noncarriers.
Among 5,752 patients of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study, we assessed the effect of pravastatin, compared with placebo, on coronary events according to 719Arg carrier status using proportional hazards models.
Since benefit from statin therapy in elderly patients has been primarily shown among those with prior vascular disease, we performed analyses in PROSPER patients with prior disease and found that pravastatin therapy significantly reduced events in 719Arg carriers hazards ratio (HR): 0.66, 95% confidence interval (CI): 0.52-0.86 but not in noncarriers (HR: 0.94, 95% CI: 0.69-1.28), P=0.09 for interaction between treatment and carrier status. Among those without prior disease, no significant benefit was observed in either carriers or noncarriers. Among those with prior vascular disease in the placebo arm, Trp719Arg heterozygotes were at significantly greater risk, compared with noncarriers (HR: 1.36, 95% CI: 1.03-1.81, P=0.03); the HR of 719Arg carriers, compared with noncarriers, was 1.28 (95% CI: 0.98-1.69, P=0.07).
Elderly carriers of the KIF6 719Arg variant with prior vascular disease received significant benefit from pravastatin therapy; no benefit was observed in noncarriers with prior disease or in those without prior disease (carriers or noncarriers).
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