Cognitive reserve and mortality in dementia: the role of cognition, functional ability and depression

OBJECTIVE: This study examined whether dementia patients with greater cognitive reserve had increased mortality rates, and whether this association was different across strata of cognition, functional ability and depression. METHODS: In the community-based Amsterdam Study of the Elderly, 261 non-institutionalized dementia patients, identified using the Geriatric Mental State Schedule (GMS), were followed for an average of 55.5 months after which mortality data were obtained. Cognitive reserve was indicated by years of education and pre-morbid intelligence (measured using the Dutch Adult Reading Test). Cognition, functional ability and depression were indicated by Mini-Mental State scores, ADL and IADL measurements and GMS depressive syndrome, respectively. RESULTS: During the follow-up 146 persons (55.9%) died. Cox regression analyses showed that more highly educated dementia patients had higher mortality rates, only if they had low MMSE scores or if they had a concurrent depression. Pre-morbid intelligence was associated with a higher mortality rate, independent of cognition, but this association was much stronger among patients with depression. The positive association between education or intelligence and mortality was not modified by functional disabilities. CONCLUSIONS: The results suggest that dementia patients with greater cognitive reserve have increased mortality rates, only if the disease has progressed to such an extent that clinical symptoms are more severe. In this respect, the reserve hypothesis needs a modification. Depression in dementia patients with greater cognitive reserve may reflect a subgroup of patients with poor prognosis.     

Risk factors for depression in later life; results of a prospective community based study (AMSTEL)

BACKGROUND: Depression in the elderly was found to be associated with a variety of risk-factors in cross sectional designs. Based on the vulnerability-stress model, etiologic pathways for depression have been suggested, with vulnerability modifying the effect of stress factors. The current prospective study tests an etiologic model for depression incidence, by assessing modifying effects of three types of vulnerability: genetic/familial vulnerability, organic vulnerability, and environmental vulnerability. METHODS: 1940 non-depressed community-living elderly were interviewed at baseline, and at follow-up three years later. Bivariate and multivariate relationships between risk factors and incident depression (GMS-AGECAT) were studied. RESULTS: Higher age, personal history of depression, death of spouse, health related factors and comorbid organic or anxiety syndrome showed significant bivariate associations with depression incidence. In multivariate analysis, the effect of stress factors on incident depression was not modified by a genetic/familial vulnerability, nor by an organic vulnerability. Effect modification by environmental factors was however evident; having a marital partner, and if unmarried having social support, significantly reduced the impact of functional disabilities on the incidence of depression. LIMITATIONS: The study consisted of two measurements with a three years interval, depressive episodes with a short duration may be under-represented. CONCLUSIONS: In the elderly, the effect of stress on incident depression is modified by environmental vulnerability. No evidence was found of effect modification by either genetic/familial or organic vulnerability. The results have implications for both recognition and treatment of late-life depression.     

Correlation Between In Vivo Antipyrine Metabolite Formation and Theophylline Metabolism in Rats

Two model substrates for oxidative hepatic enzyme activity, viz. antipyrine (A) and theophylline (T), were given simultaneously to rats by iv administration. Blood concentrations of A and T were measured by a high-performance liquid chromatographic (HPLC) method. Urinary excretions of A, T, and the major metabolites arising from A—4-hydroxyantipyrine (OHA), norantipyrine (NORA), 3-hydroxymethylantipyrine (HMA), and 4,4-dihydroxyantipyrine (DOHA)—and from T—1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU)—were also determined by HPLC. It was found that the pharmacokinetic parameters obtained after the simultaneous administration of A and T at relatively low dose levels (A, 5.0 mg; and T, 1.3 mg) were not different from those obtained after the separate administration of A or T at the same dose level. In order to investigate whether the metabolic pathways of A and T are mediated by the same or closely related forms of the cytochrome P-450 system, metabolic clearances of A (CL_A,M) and T (CL_T,M) and the clearances for production of their various metabolites, obtained in untreated rats and in rats pretreated with 3-methylcholanthrene (MC) or with MC followed by 9-hydroxyellipticine (E), were correlated. These two compounds are a selective cytochrome P-448 inducer and inhibitor, respectively. Strong correlations were found between CL_T,M and the clearances for production of OHA, NORA, and DOHA but not HMA. The best correlation, however, was observed between CL_T,M and CL_OHA, not only when all data points were taken into account (r = 0.99), but also in separate pretreatment groups (r ranging from 0.87 to 0.92). Moreover, the slopes of these correlation lines varied only slightly among groups, while the intercepts were not significantly different from zero. In the separate pretreatment groups, the correlation coefficients for the correlations between CL_T,M and the clearance for production of the other metabolites of A were considerably lower, while the slopes of the correlation lines varied substantially. Clearances for production of the metabolites of T were strongly correlated with each other (r = 0.99) and with CL_OHA (r = 0.95). It can be concluded that theophylline metabolism and formation of OHA are mediated by the same or very similar forms of cytochrome P-450, whereas formation of the other major metabolites of A is not or only partly. The study of the various pathways of metabolism after simultaneous administration of drugs is a powerful tool in the study of correlations in drug metabolism in vivo.     

Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study.

BACKGROUND: Depressive symptoms have been suggested to increase the risk of cardiovascular diseases, but this may reflect reversed causality. We investigated to what extent depressive symptoms are a true risk factor for cardiovascular mortality in elderly men. DESIGN: The Finland, Italy and Netherlands Elderly (FINE) study is a prospective cohort study conducted in Finland, Italy and The Netherlands. METHODS: Depressive symptoms were measured with the Zung self-rating Depression Scale in 799 elderly men, aged 70-90 years, free from cardiovascular diseases. Using Cox models, hazard ratios (HRs) were calculated for specific cardiovascular mortality endpoints. The analyses were adjusted for potential confounders, stratified on country and repeated after exclusion of men who died from cardiovascular diseases up to 5 years after baseline. RESULTS: During 10-years of follow-up 224 (28%) men died from cardiovascular diseases. The adjusted hazard for a five-point increase in depressive symptoms was 1.15 [95% confidence interval (CI) 1.08-1.23] for cardiovascular mortality. This risk was stronger for mortality from stroke (HR 1.35; 95% CI 1.19-1.53) and heart failure (HR 1.16; 95% CI 1.00-1.35) in comparison with mortality from coronary heart disease (HR 1.08; 95% CI 0.97-1.20) and other degenerative heart diseases (HR 1.06; 95% CI 0.91-1.23). Exclusion of men who died from cardiovascular diseases within 5 years after baseline did not change the strength of the associations. There were no significant differences in HRs between northern and southern Europe. CONCLUSIONS: This study provides further and more convincing prospective evidence for depressive symptoms as a risk factor for cardiovascular mortality in elderly men.     

Risk factors for calcification of the vertebrobasilar arteries in cardiovascular patients referred for a head CT,the SMART study

Background and purposeVertebrobasilar artery calcification (VBAC) has been associated with increased stroke occurrence. Little is known on VBAC risk factors, especially for patients with cardiovascular disease. We aimed to assess risk factors associated with VBAC in a cohort of cardiovascular patients referred for a head computed tomography (CT) scan.Materials and methodsAll patients who underwent a clinically indicated, unenhanced, thin slice head CT 6 months before or after inclusion in the SMART study were included. CTs were assessed for presence of VBAC (dichotomously). Relative risks of the associations of age, sex, diabetes mellitus (DM), obesity, body mass index, estimated glomerular filtration rate, hypertension, hyperlipidemia, use of lipid lowering medication, smoking status, high sensitivity C-reactive protein, ankle-brachial index (ABI; ≤ 0.90, ≥ 1.30, continuous), internal carotid artery stenosis ≥ 70%, and carotid intima-media thickness (IMT) with VBAC were estimated using Poisson regression analysis with robust standard errors, adjusted for age and sex.ResultsOf the 471 patients included (57% male, median age 58 [interquartile range 47–63]), 117 (24.8%) showed VBAC. Presence of VBAC was associated with older age (RR per 10 years = 1.70 [95%CI 1.46–1.99]), DM (RR = 1.45 [95%CI 1.03–2.06]), obesity (RR = 1.53 [95%CI 1.10–2.12]), ABI ≤ 0.90 (RR = 1.57 [95%CI 1.02–2.41]), and an increased carotid IMT (RR = 2.60 per mm [95%CI 1.20–5.62]). Other measurements were not associated with VBAC.ConclusionsWe identified several markers associated with VBAC in patients with cardiovascular disease referred for a head CT. Future investigation into the relationship between VBAC and stroke is warranted to determine the potential of VBAC in stroke prevention.     

Reduced parenchymal cerebral blood flow is associated with greater progression of brain atrophy: The SMART-MR study

Global cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 ± 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: –0.23 to –0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: –0.29 to –0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time (p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF (p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration.     

Self-rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study

Abstract. Grool AM, van der Graaf Y, Visseren FLJ, de Borst GJ, Algra A, Geerlings MI, on behalf of the SMART Study Group (University Medical Center Utrecht, Utrecht, The Netherlands). Self‐rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study. J Intern Med 2012; 272: 277–286. Objectives. Lower self‐rated health status has been associated with worse prognosis in patients with coronary artery disease (CAD). We investigated the influence of self‐rated physical and mental health status on the risk of future vascular events and mortality for various locations of symptomatic atherosclerotic disease and asymptomatic disease. Design. Patients with CAD (n = 2547), cerebrovascular disease (n = 1061), peripheral arterial disease (PAD; n = 648), abdominal aortic aneurysm (AAA; n = 272) and asymptomatic atherosclerotic disease (n = 1933) were followed for a median of 4 years for the occurrence of a new vascular event or death. Self‐rated health status was assessed with the Short Form‐36 physical and mental component summary scales. Cox regression models were used to estimate associations between health status and vascular events and death, adjusted for age, sex, vascular risk factors and intima–media thickness. Results. In the total population, lower self‐rated physical health status (per 10‐point decrease) increased the risk of vascular events [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.24–1.52], and all‐cause (HR = 1.45, 95% CI 1.29–1.63) and vascular mortality (HR = 1.40, 95% CI 1.20–1.64). A 10‐point decrease in mental health status was associated with a modest increase in the risk of vascular events (HR = 1.19, 95% CI 1.08–1.32), and all‐cause (HR = 1.19, 95% CI 1.05–1.34) and vascular mortality (HR = 1.28, 95% CI 1.09–1.49). Risk estimates of physical and mental health status were highest in patients with asymptomatic atherosclerotic disease and lowest in those with PAD. Conclusions. Poorer self‐rated physical and mental health status increases the risk of vascular events and mortality in a broad population of patients with symptomatic and asymptomatic atherosclerotic disease.     

The Development of a Decision Tool for the Empiric Treatment of Suspected Urinary Tract Infection in Frail Older Adults: A Delphi Consensus Procedure

Objectives

Nonspecific signs and symptoms combined with positive urinalysis results frequently trigger antibiotic therapy in frail older adults. However, there is limited evidence about which signs and symptoms indicate urinary tract infection (UTI) in this population. We aimed to find consensus among an international expert panel on which signs and symptoms, commonly attributed to UTI, should and should not lead to antibiotic prescribing in frail older adults, and to integrate these findings into a decision tool for the empiric treatment of suspected UTI in this population.

Do severity and duration of depressive symptoms predict cognitive decline in older persons? Results of the Longitudinal Aging Study Amsterdam

BACKGROUND AND AIMS: Some prospective studies show that depression is a risk factor for cognitive decline. So far, the explanation for the background of this association has remained unclear. The present study investigated 1) whether depression is etiologically linked to cognitive decline; 2) whether depression and cognitive decline may be the consequence of the same underlying subcortical pathology, or 3) whether depression is a reaction to global cognitive deterioration. METHODS: A cohort of 133 depressed and 144 non-depressed older persons was followed at eight successive observations over 3 years. All subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). Depression symptoms were measured by means of the CES-D at eight successive waves. Cognitive function (memory function, information processing speed, global cognitive functioning) was assessed at baseline and at the last CES-D measurement. RESULTS: The severity and duration of depressive symptoms were not associated with subsequent decline in memory functioning or global cognitive decline. There was an association between both chronic mild depression and chronic depression, and decline in speed of information processing. CONCLUSIONS: These results support the hypothesis that, in older persons, chronic depression as well as cognitive decline may be the consequence of the same underlying subcortical pathology.