Population-based study of baseline ethanol consumption and risk of incident essential tremor

Recent postmortem studies have demonstrated pathological changes, including Purkinje cell loss, in the cerebellum in essential tremor (ET). Toxic exposures that compromise cerebellar tissue could lower the threshold for developing ET. Ethanol is a well-established cerebellar toxin, resulting in Purkinje cell loss

Population-based prospective study of cigarette smoking and risk of incident essential tremor

Background: Smoking cigarettes is associated with lower risk of Parkinson disease (PD). Despite the clinical links between PD and essential tremor (ET), there are few data on smoking in ET. One study showed an association between smoking and lower ET prevalence. We now study whether baseline smoking is associated with lower risk of incident ET. Methods: Using a population-based, cohort design, baseline cigarette smoking habits were assessed in 3,348 participants in an epidemiologic study in Spain, among whom 77 developed incident ET. Results: There were 3,348 participants, among whom 397 (11.9%) were smokers at baseline. Five (6.5%) of 77 incident ET cases had been smokers at baseline, compared with 392 (12.0%) of 3,271 controls (p = 0.14). Baseline pack-years were lower in incident ET cases than in controls (9.2 ± 17.7 vs 15.7 ± 28.4, p = 0.002). Participants were stratified into baseline pack-year tertiles, and few incident ET cases were in the highest tertile (4 [5.2%] cases vs 431 [13.2%] controls, p = 0.039). In Cox proportional hazards models, the highest baseline pack-year tertile was associated with lower risk of incident ET; those in the highest pack-year tertile were one-third as likely to develop ET when compared with nonsmokers (relative risk [RR] 0.37, 95% CI 0.14—1.03, p = 0.057 [unadjusted model] and RR 0.29, 95% CI 0.09—0.90, p = 0.03 [adjusted model]). Conclusions: We demonstrated an association between baseline heavy cigarette smoking and lower risk of incident essential tremor. The biologic basis for this association requires future investigation

Philadelphia Geriatric Morale Scale in essential tremor : a population-based study in three Spanish communities

Essential tremor (ET) is associated with both functional disability and depression. Each could contribute to a poor sense of well-being and low morale. We hypothesized that morale would be lower in ET cases than controls. Using a population-based, cross-sectional design, morale was assessed in 187 ET cases and 561 matched controls living in three communities in central Spain using the Philadelphia Geriatric Center Morale Scale (PGCMS) (range = 0 [low morale]-17), which included three-dimensions of psychological well-being: agitation, lonely dissatisfaction, and attitude toward own aging. The PGCMS score was lower in ET cases than controls (9.41 ± 3.21 vs. 10.39 ± 2.92, P < 0.001), as were the Agitation subscore (3.17 ± 1.71 vs. 3.78 ± 1.67, P < 0.001) and Lonely Dissatisfaction subscore (3.75 ± 1.34 vs. 4.02 ± 1.24, P < 0.05). Nearly one-half of the ET cases were classified as having low morale compared with only one-third of controls (P = 0.006). In a linear regression analysis adjusting for demographic factors and multiple comorbid conditions, ET cases had a lower log PGCMS score than controls (P < 0.001). Exclusion of participants on antidepressant medication did not change the results. Our results indicate that morale is significantly lower in community-dwelling ET cases than in matched controls. This lower morale could in part be a proxy for mild, untreated depression. It therefore seems important to detect and then possibly treat this problem to improve the psychological well-being of patients with this disease

Statins and cognitive functioning in the elderly: a population-based study

In a 2009 Cochrane review, the authors concluded that there is good evidence that statins, given in late life to people at risk of vascular disease, have no effect in preventing Alzheimer's disease or dementia. A related issue, which remains unclear, is whether statins improve cognitive function. While some studies have shown a beneficial effect of statins on cognitive function, others have observed mild detrimental effects on cognition. Our aim was to assess cognitive function in community-dwelling elderly participants treated with statins compared with their untreated counterparts (i.e., controls) living in the same population. 137 population-dwelling participants who were receiving statins and 411 matched controls age ⩾ 65 years (median=72 years) in central Spain (the Neurological Disorders in Central Spain [NEDICES] study) underwent a neuropsychological assessment, including tests of global cognitive performance, frontal-executive function, verbal fluency, and memory. Median duration of statin treatment was 2 years. Of 137 participants receiving statins, 53 (38.7%) were taking pravastatin, 38 (27.7%) simvastatin, 37 (27.0%) lovastatin, 6 (4.4%) fluvastatin, and 3 (2.2%) atorvastatin. Although initial univariate analyses indicated some differences, after adjusting for age, gender, education, depressive symptoms, premorbid intelligence, medications that potentially affect cognitive function, and blood cholesterol levels, statin users and controls performed similarly on all neuropsychological tests. In this population-based sample, elderly participants treated with statins and untreated controls performed similarly in all tested cognitive areas. These results do not support a positive benefit of statins on cognition

Downregulation of ERK1/2 activity by CaMKII modulates p21Cip1 levels and survival of immortalized lymphocytes from Alzheimer’s disease patients

11 páginas, 9 figuras, 2 tablas -- PAGS nros. 1090-1100Previously, we reported a Ca2+/calmodulin (CaM)-dependent impairment of apoptosis induced by serum deprivation in Alzheimer’s disease (AD) lymphoblasts. These cell lines showed downregulation of extracellular signal-regulated kinase (ERK)1/2 activity and elevated content of p21 compared with control cells. The aim of this study was to delineate the molecular mechanism underlying the distinct regulation of p21 content in AD cells. Quantitative reverse transcription polymerase chain reaction analysis demonstrated increased p21 messenger RNA (mRNA) levels in AD cells. The ERK1/2 inhibitor, PD98059, prevented death of control cells and enhanced p21 mRNA and protein levels. The CaM antagonist, calmidazolium, and the CaMKII inhibitor, KN-62, normalized the survival pattern of AD lymphoblasts by augmenting ERK1/2 activation and reducing p21 mRNA and protein levels. Upregulation of p21 transcription in AD cells appears to be the consequence of increased activity of forkhead box O3a (FOXO3a) as the result of diminished ERK1/2-mediated phosphorylation of this transcription factor, which in turn facilitates its nuclear accumulation. Murine double minute 2 (MDM2) protein levels were decreased in AD cells relative to control lymphoblasts, suggesting an impairment of FOXO3a degradationThis work has been supported by grants from Ministerio de Economía y Competitividad (SAF2007-624505, SAF2011-28603) and Fundación Ramón Areces to A.M.-R. N.E. holds a fellowship of the JAE predoctoral program of the CSICPeer reviewe

Non-steroidal anti-inflammatory drugs use in older adults decreases risk of Alzheimer's disease mortality.

[EN]Alzheimer disease (AD) mortality risk in a large cohort of subjects treated or not with non-steroidal anti-inflammatory drugs (NSAIDs) is unknown. Our objective was to determine whether NSAIDs use is associated with decreased risk of AD mortality. In this prospective, population-based study (Neurological Disorders in Central Spain [NEDICES]) of 5,072 people without AD (aged 65 years and older), sociodemographic, comorbidity factors, and current medications were recorded at baseline. Community-dwelling older adults were followed for a median of 12.7 years, after which the death certificates of deceased participants were examined. 2,672 (52.7%) of 5,072 participants died, including 504 (18.9%) NSAIDs users and 2,168 (81.1%) non-users. Of the 2,672 deceased participants, 113 (4.2%) had AD as a cause of death (8 [1.6%] among NSAIDs users and 105 [4.8%] among non-users, chi-square = 10.70, p = 0.001). In an unadjusted Cox model, risk of AD mortality was decreased in NSAIDs users (hazard ratio [HR] for AD mortality = 0.35, 95% confidence interval [CI] 0.17–0.72, p = 0.004) when compared to non-users. After adjusting for numerous demographic factors and co-morbidities, the HR for AD mortality in NSAIDs users was 0.29, 95% CI 0.12–0.73, p = 0.009. Stratified analyses showed a significantly decreased risk of AD mortality with aspirin, whereas non-aspirin NSAIDs only showed a statistical trend toward significance in the adjusted Cox regression models. NSAIDs use was associated with 71% decreased risk of AD mortality in older adults. Our results support the hypothesis that NSAIDs use is a protective factor of developing AD

Under reporting of Parkinson’s disease on death certificates: a population-based study (NEDICES)

Background Parkinson's disease is frequently omitted as a cause of death from death certificates. A limitation of previous studies that attempted to assess the validity of death certificates is that population-dwelling cases, with milder, undiagnosed Parkinson's disease were likely excluded. As a result, those studies likely overestimated the validity of death certificates because they did not include these milder cases. We assessed the validity of death certificates in a prospective population-based study (NEDICES), which includes previously undiagnosed Parkinson's disease cases detected during the assessment. Methods 3926 community-dwelling elderly subjects with and without Parkinson's disease were followed during a median of 12.6 years, after which the death certificates of those who died were examined. We calculated the proportion of cases of clinically diagnosed Parkinson's disease for whom a diagnosis of Parkinson's disease was certified as the basic cause of death on death certificates. Results 1791 (45.6%) of the 3926 participants died over a median follow-up of 7.1 years, including 82 (73.9%) deaths among 111 participants with Parkinson's disease. Parkinson's disease was rarely certified as the basic cause of death (14.6%). Gender, disease stage and the period during which the study was conducted (i.e., 1994 to 2007) did not influence the likelihood that Parkinson's disease would be reported. Conclusions Our findings reinforce the notion that the reporting of Parkinson's disease on death certificates remains poor. This suggests a lack of awareness of the importance of Parkinson's disease as a cause of death.pre-print261 K

Association between Parkinson's disease and diabetes: Data from NEDICES study

Background: Despite growing evidence showing an association between Parkinson's disease (PD) and diabetes, epidemiological studies have shown conflicting results. Aims of the study: To evaluate the association between PD and diabetes and the impact of diabetes duration in this association in an elderly (≥65 years) Spanish population. Methods: Data for this cross-sectional population-based analysis were obtained from NEDICES study. Subjects were identified from census list. Diagnosis of PD was confirmed by neurological examination. Diabetes was defined by self-report, being on antidiabetic medication or diagnosis on medical records. Logistic regression analysis adjusted by potential confounders was performed to estimate the association between both conditions and also after dividing patients into short-duration (<10 years) and long-duration (≥10 years) diabetes. Results: A total of 4998 subjects were included (79 PD and 4919 controls). Univariate analysis did not show any association between prevalence of PD and diabetes (OR 1.89, 95% CI 0.90-3.98, P=.09), although subgroup analysis showed a positive association in those with long-duration diabetes (3.27, 95% CI 1.21-8.85, P=.02). Conclusions: Diabetes duration might be an important factor in the association between PD and diabetes, and the risk might be limited to those with longer disease duration

Medical, environmental and personal factors of disability in the elderly in Spain: a screening survey based on the International Classification of Functioning

Malalties cròniques; Demència; Avaluació de la discapacitatEnfermedades crónicas; Demencia; Evaluación de la discapacidadChronic diseases; Dementia; Disability evaluationObjectives: The International Classification of Functioning, Disability and Health (ICF) advocates a multifactorial and multifaceted conceptualization of disability. The objective of this study was to ascertain major medical, environmental and personal determinants of severe/extreme disability among the elderly population in Spain. The assessment scheme was consistent with the ICF model of disability.Methods: Nine populations contributed probabilistic or geographically-defined samples following a two-phase screening design. The Mini-Mental State Examination and the 12-item version of the World Health Organization-Disability Assessment Schedule, 2(nd) ed. (WHO-DAS II), were used as cognitive and disability screening tools, respectively. Positively screened individuals underwent clinical work-up for dementia and were administered the 36-item version of the WHO-DAS II to estimate ICF disability levels. We used logistic regression for the purposes of data combination, adjusted for age and sex in all analyses. Results: The sample was composed of 503 participants aged ≥ 75 years. Alzheimeŕs disease and depression were highly predictive of severe/extreme disability (OR: 17.40, 3.71). Good access to social services was strongly associated with a low level or absence of disability (OR: 0.05 to 0.18). Very difficult access to services and having dementia or another psychiatric disorder were associated with an increase in disability (OR: 66.06). There was also a significant interaction effect between access to services and neurological disorders (OR: 12.74).Conclusions: Disability is highly prevalent among the Spanish elderly and is influenced by medical, social and personal factors. Disability could potentially be reduced by ensuring access to social services, preventing dementia and stroke, and treating depression.This project, led by J. de Pedro-Cuesta, was supported by thePfizer Foundation and by the RECSP C03-09, CIEN C03-06 and CIBERNED and CIBERSAM research network