The health status: the ignored risk factor in dementia incidence. NEDICES cohort.

BACKGROUND: The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF. AIM: To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis. METHODS: We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years. RESULTS: Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders. DISCUSSION: According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults. CONCLUSIONS: Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

Predementia constructs: Mild cognitive impairment or mild neurocognitive disorder? A narrative review.

BACKGROUND: Predementia is a heuristic umbrella concept to classify older adults with cognitive impairment who do not suffer dementia. Many diagnostic entities have been proposed to address this concept, but most of them have not had widespread acceptance. AIMS: To review clinical definitions, epidemiologic data (prevalence, incidence) and rate of conversion to dementia of the main predementia constructs, with special interest in the two most frequently used: mild cognitive impairment (MCI) and minor neurocognitive disorder (miNCD). METHODS: We have selected in three databases (MEDLINE, Web of Science and Google scholar) the references from inception to 31 December 2019 of relevant reviews, population and community-based surveys, and clinical series with >500 participants and >3 years follow-up as the best source of evidence. MAIN RESULTS: The history of predementia constructs shows that MCI is the most referred entity. It is widely recognized as a clinical syndrome harbinger of dementia of several etiologies, mainly MCI due to Alzheimer's disease. The operational definition of MCI has shortcomings: vagueness of its requirement of "preserved independence in functional abilities" and others. The recent miNCD construct presents analogous difficulties. Current data indicate that it is a stricter predementia condition, with lower prevalence than MCI, less sensitivity to cognitive decline and, possibly, higher conversion rate to dementia. CONCLUSIONS: MCI is a widely employed research and clinical entity. Preliminary data indicate that the clinical use of miNCD instead of MCI requires more scientific evidence. Both approaches have common limitations that need to be addressed.

Characterizing functional alterations in instrumental activities of daily living using latent class analysis: a population-based study (NEDICES).

Background and Objectives: The existence of different patterns of functional impairment in older adults has scarcely been addressed. This research investigates major patterns of functional impairment based on Pfeffer's Functional Activity Questionnaire (FAQ).Research Design and Methods: The participants come from NEDICES (Neurological Disorders in Central Spain), a prospective population-based cohort study. A total of 3837 individuals without dementia who completed the Spanish version of the FAQ was selected. Latent Class Analysis (LCA) was carried out to examine potential cluster subgroups based on FAQ responses.Results: The FAQ showed good internal consistency (Cronbach's alpha: 0.86) and moderate correlation (r = -.40) with cognitive performance on the Mini-Mental State Examination (MMSE-37). The response patterns revealed the presence of three latent classes: absence of functional alteration (Class 1), established functional alteration (Class 2), and minimal functional alteration (Class 3). Moreover, the probability of resolving Items 2 ('shopping alone for…'), 3 ('heating water…'), 4 ('preparing a balanced meal'), and 9 ('travelling out of neighbourhood…') was close to 0% for Class 2 membership, while those with the lowest probability of resolution for Class 3 were Items 2 and 9. Items 3 and 4 were the best to discriminate between different grades of functional alterations (Class 2 vs. Class 3).Discussion and Implications: Our findings indicate that the combination of overall FAQ score and item response pattern may help to classify individuals with different subtypes of functional impairment. The Spanish version of the FAQ is a useful tool for detection of functional impairment in older adults.

Salivary lactoferrin as biomarker for Alzheimer's disease: Brain-immunity interactions.

OBJECTIVE: We aim to explain why salivary lactoferrin (Lf) levels are reduced in patients suffering mild cognitive impairment (MCI) and sporadic Alzheimer's disease (sAD).1 We also will discuss if such Lf decrease could be due to a downregulation of the sAD associated systemic immunity. BACKGROUND: Several non-neurological alterations have been described in sAD, mainly in skin, blood cell, and immunological capacities. We reviewed briefly the main pathophysiological theories of sAD (amyloid cascade, tau, unfolder protein tau, and amyloid deposits) emphasizing the most brain based hypotheses such as the updated tau-related neuron skeletal hypothesis; we also comment on the systemic theories that emphasize the fetal origin of the complex disorders that include the low inflammatory and immunity theories of sAD. NEW/UPDATED HYPOTHESIS: Lf has important anti-infectious and immunomodulatory roles in health and disease. We present the hypothesis that the reduced levels of saliva Lf could be an effect of immunological disturbances associated to sAD. Under this scenario, two alternative pathways are possible: first, whether sAD could be a systemic disorder (or disorders) related to early immunological and low inflammatory alterations; second, if systemic immunity alterations of sAD manifestations could be downstream of early sAD brain affectations. MAJOR CHALLENGES FOR THE HYPOTHESIS: The major challenge of the Lf as early sAD biomarker would be its validation in other clinical and population-based studies. It is possible the decreased salivary Lf in early sAD could be related to immunological modulation actions, but other different unknown mechanisms could be the origin of such reduction. LINKAGE TO OTHER MAJOR THEORIES: This hypothesis is in agreement with two physiopathological explanations of the sAD as a downstream process determined by the early lesions of the hypothalamus and autonomic vegetative system (neurodegeneration), or as a consequence of low neuroinflammation and dysimmunity since the early life aggravated in the elderly (immunosenescence).

Remote Monitoring of Treatment Response in Parkinson's Disease: The Habit of Typing on a Computer.

OBJECTIVE: The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting. METHODS: We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome. RESULTS: The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward. CONCLUSIONS: This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society.

Tremor severity in Parkinson's disease and cortical changes of areas controlling movement sequencing: A preliminary study.

There remains much to learn about the changes in cortical anatomy that are associated with tremor severity in Parkinson's disease (PD). For this reason, we used a combination of structural neuroimaging to measure cortical thickness and neurophysiological studies to analyze whether PD tremor was associated with cortex integrity. Magnetic resonance imaging and neurophysiological assessment were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly tremor-dominant phenotype. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis software. Assessment of tremor was performed by means of high-density surface electromyography (hdEMG) and inertial measurement units (IMUs). Individual motor unit discharge patterns were identified from surface hdEMG and tremor metrics quantifying motor unit synchronization from IMUs. Increased motor unit synchronization (i.e., more severe tremor) was associated with cortical changes (i.e., atrophy) in wide-spread cortical areas, including caudal middle frontal regions bilaterally (dorsal premotor cortices), left inferior parietal lobe (posterior parietal cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left posterior and transverse temporal cortex, and left occipital lobe, as well as reduced left middle temporal volume. Given that the majority of these areas are involved in controlling movement sequencing, our results support Albert's classic hypothesis that PD tremor may be the result of an involuntary activation of a program of motor behavior used in the genesis of rapid voluntary alternating movements.

Spanish version of the Mattis Dementia Rating Scale-2 for early detection of Alzheimer's disease and mild cognitive impairment.

OBJECTIVE: We aimed to analyse the clinical utility of the Mattis Dementia Rating Scale (MDRS-2) for early detection of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) in a sample of Spanish older adults. METHODS: A total of 125 participants (age = 75.12 ± 6.83, years of education =7.08 ± 3.57) were classified in three diagnostic groups: 45 patients with mild AD, 37 with amnestic MCI-single and multiple domain and 43 cognitively healthy controls (HCs). Reliability, criterion validity and diagnostic accuracy of the MDRS-2 (total and subscales) were analysed. The MDRS-2 scores, adjusted by socio-demographic characteristics, were calculated through hierarchical multiple regression analysis. RESULTS: The global scale had adequate reliability (α = 0.736) and good criterion validity (r = 0.760, p < .001) with the Mini-Mental State Examination. The optimal cut-off point between AD patients and HCs was 124 (sensitivity [Se] = 97% and specificity [Sp] = 95%), whereas 131 (Se = 89%, Sp = 81%) was the optimal cut-off point between MCI and HCs. An optimal cut-off point of 123 had good Se (0.97), but poor Sp (0.56) to differentiate AD and MCI groups. The Memory and Initiation/Perseveration subscales had the highest discriminative capacity between the groups. CONCLUSIONS: The MDRS-2 is a reliable and valid instrument for the assessment of cognitive impairment in Spanish older adults. In particular, optimal capacity emerged for the detection of early AD and MCI. Copyright © 2017 John Wiley & Sons, Ltd.

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain.

BACKGROUND: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. METHODS: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). RESULTS: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95%CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. CONCLUSIONS: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain.

Inter-Rater Agreement in the Clinical Diagnosis of Cognitive Status: Data from the Neurological Disorders in Central Spain 2 Pilot Study.

BACKGROUND: To assess the diagnostic agreement of cognitive status (dementia, mild cognitive impairment (MCI), normal cognition) among neurologists in the field of neurological disorders in Central Spain 2 study. METHODS: Full medical histories of 30 individuals were provided to 27 neurologists: 9 seniors, 10 juniors and 8 residents. For each case, we were asked to assign a diagnosis of dementia, MCI or normal cognition using the National Institute on Aging-Alzheimer's Association workgroup (NIA-AA) core clinical criteria for all-cause dementia, Winblad et al. criteria for MCI, and analyze intensity and etiology if dementia was diagnosed. Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics. RESULTS: Overall inter-rater agreement on cognitive status was κ = 0.76 (95% CI 0.65-0.86), being slightly higher among junior neurologists (κ = 0.85, 95% CI 0.73-0.95) than among seniors (κ = 0.71, 95% CI 0.59-0.83) and residents (κ = 0.69, 95% CI 0.54-0.81) but without statistical significance among groups. Dementia severity showed an overall κ of 0.34, 0.44 and 0.64 for mild, moderate and severe dementia respectively. CONCLUSIONS: Substantial agreement was demonstrated for the diagnosis of cognitive status (dementia, MCI and normal cognition) among neurologists of different levels of experience in a population-based epidemiological study using NIA-AA and Winblad et al. CRITERIA: The agreement rate was lower in the diagnosis of dementia severity.

Physical Activity as Protective Factor against Dementia: A Prospective Population-Based Study (NEDICES).

The aim of this study was to analyze whether physical activity (PA) is a protective factor for the incidence of dementia after 3 years of follow-up. The Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of older adults (age 65 years and older) that comprised 5278 census-based participants at baseline (1994-1995). A broad questionnaire was used to assess participants' sociodemographic characteristics, health status, and lifestyle. Subsequently, a modified version of Rosow-Breslau questionnaire was applied to classify individuals' baseline PA into groups (i.e., sedentary, light, moderate, and high). Cox regression models adjusted for several covariates (age, sex, education, previous stroke, alcohol consumption, hypertension, health related variables) were carried out to estimate the association between the PA groups and risk of dementia at the 3-year follow-up (1997-1998). A total of 134 incident dementia cases were identified among 3105 individuals (56.6% female; mean age=73.15 ± 6.26) after 3 years. Hazard ratios (HRs) of the light, moderate, and high PA groups (vs. sedentary group) were 0.40 (95% confidence interval {CI} [0.26, 0.62]; p<.001), 0.32 (95% CI [0.20, 0.54]; p<.001) and 0.23 (95% CI [0.13, 0.40]; p<.001), respectively. Even after controlling for covariates and the exclusion of doubtful dementia cases, HRs remained significant. However, a supplementary analysis showed that the dose-effect hypothesis did not reach statistical significance. PA is a protective factor of incident dementia in this population-based cohort.

Polypharmacy in the Elderly: A Marker of Increased Risk of Mortality in a Population-Based Prospective Study (NEDICES).

BACKGROUND: Little information is available on the potential association between polypharmacy and risk of mortality. OBJECTIVE: To determine in a population-based study whether polypharmacy is associated with increased risk of mortality in elderly persons. METHODS: In this population-based, prospective study of 5,052 people aged 65 years and older (Neurological Disorders in Central Spain), current medications were recorded. Cox proportional hazards models, adjusted for sociodemographics and comorbidity factors, were used to assess the risk of death up to 13.3 years later, comparing the polypharmacy group (≥6 drugs) to those who were taking 1-5 drugs and those in a nonmedicated group (0 drugs). RESULTS: Out of 5,052 participants, 2,550 (50.5%) died over a median follow-up of 6.5 years, including 361 (28.8%) deaths among 931 nonmedicated participants, 1,946 (51.4%) deaths among 3,787 participants taking 1-5 drugs daily, and 243 (72.8%) among 334 participants on polypharmacy. In an unadjusted Cox model, risk of mortality was increased in participants on polypharmacy [hazard ratio (HR) = 2.78, 95% confidence interval [CI]: 2.36-3.27, p < 0.001) and in those taking between 1 and 5 drugs (HR = 1.47, 95% CI: 1.31-1.64, p < 0.001) versus those who were nonmedicated (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, HR remained increased in participants on polypharmacy (HR = 1.83, 95% CI: 1.51-2.21, p < 0.001). CONCLUSION: This study provides evidence that polypharmacy is associated with increased risk of mortality in elderly people. The extent to which polypharmacy is the proximate cause rather than a marker of this increase risk remains to be determined.

Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History.

Background: The concept of Alzheimer disease (AD)-since its histological discovery by Alzheimer to the present day-has undergone substantial modifications. Methods: We conducted a classical narrative review of this field with a bibliography selection (giving preference to Medline best match). Results: The following subjects are reviewed and discussed: Alzheimer's discovery, Kraepelin's creation of a new disease that was a rare condition until the 1970's, the growing interest and investment in AD as a major killer in a society with a large elderly population in the second half of the 20th century, the consolidation of the AD clinicopathological model, and the modern AD nosology based on the dominant amyloid hypothesis among many others. In the 21st century, the development of AD biomarkers has supported a novel biological definition of AD, although the proposed therapies have failed to cure this disease. The incidence of dementia/AD has shown a decrease in affluent countries (possibly due to control of risk factors), and mixed dementia has been established as the most frequent etiology in the oldest old. Conclusions: The current concept of AD lacks unanimity. Many hypotheses attempt to explain its complex physiopathology entwined with aging, and the dominant amyloid cascade has yielded poor therapeutic results. The reduction in the incidence of dementia/AD appears promising but it should be confirmed in the future. A reevaluation of the AD concept is also necessary.

Reported head trauma and odds of acute ischemic stroke or transient ischemic attack: A population-based study (NEDICES).

BACKGROUND: Six previous observational studies have found a higher risk for stroke among traumatic head injury survivors. However, these studies have used record linkage systems, which could lead to underestimating stroke numbers. This study aims to reexamine the relationship between head trauma and the risk of ischemic stroke/transient ischemic attack (TIA) in an older population using data from the Neurological Disorders in Central Spain (NEDICES) study, a population-based study that includes rigorous clinical examinations for patients with suspected neurological diseases. METHODS: We asked participants if they had ever experienced head trauma that was severe enough to warrant a consult with a physician, leading, among others, to visiting the emergency room, hospitalization, or resulting in loss of consciousness. The history of head trauma was evaluated in 196 (5.7%) acute ischemic stroke/TIA cases and 3256 controls in the NEDICES study. RESULTS: Among the final sample of 3452 participants, 354 (10.3%) subjects had a history of head trauma. Twenty-nine (14.8%) of 196 acute ischemic stroke/TIA cases vs. 325 (10.0%) of 3256 controls reported a history of head trauma (p = 0.039). In a regression analysis that adjusted for several variables (age in years, sex, educational level, ever smoker, ever drinker, diabetes mellitus, arterial hypertension, and heart disease), the odds ratio was 1.54 (95% CI = 1.02-2.35, p = 0.042). CONCLUSIONS: The reported head injury was associated with a 54% higher probability of acute ischemic stroke/TIA. More research is needed to confirm these findings, especially using population-based longitudinal studies.

Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights.

Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer's disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols.

Short sleep duration heralds essential tremor: a prospective, population-based study.

Lewy bodies have been described in the locus coeruleus of some patients with essential tremor (ET), and this brainstem nucleus plays an important role in sleep cycle regulation. Despite this, no studies have investigated the relationship between daily sleep duration and the risk of ET. We determined whether baseline daily sleep duration was associated with an increased risk of incident ET. In this prospective, population-based study of individuals > 65 years of age (the Neurological Disorders in Central Spain [NEDICES] cohort), participants were evaluated at baseline and 3 years later. At baseline, participants indicated their daily sleep duration as the sum of nighttime sleep and daytime napping. The average daily total sleep duration was grouped into four categories: ≤ 5 hours (short sleepers), 6 hours, 7 to 8 hours (reference), and ≥ 9 hours (long sleepers) hours. In total, 3,303 participants had a median duration of follow-up of 3.3 years. There were 76 incident ET cases at follow-up. The relative risks for short sleepers and for long sleepers were 2.25 (95% confidence interval [CI], 1.21-4.16; P = 0.01) and 0.74 (95% CI, 0.41-1.32; P = 0.31), respectively. After adjustment for potential confounders, including age, sex, educational level, current smoker, current drinker, and depressive symptoms or antidepressant use, the risk remained significantly increased for short sleepers (relative risk, 1.95; 95% CI, 1.03-3.70; P = 0.04]). The results indicated that short daily sleep duration may be a pre-motor marker for ET. Additional prospective studies are needed to confirm these results, and the biological basis for this association merits additional investigation.

Rate of cognitive decline in premotor Parkinson's disease: a prospective study (NEDICES).

Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population-based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non-PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994-95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997-98, but not at baseline). A 37-item version of the Mini-Mental State Examination (37-MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37-MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3-year follow-up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal-Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD.

The ability of self-rated health to predict mortality among community-dwelling elderly individuals differs according to the specific cause of death: data from the NEDICES cohort.

BACKGROUND: The biomedical and psychosocial mechanisms underlying the relationship between self-rated health (SRH) and mortality in elderly individuals remain unclear. OBJECTIVE: To assess the association between different measurements of subjective health (global, age-comparative, and time-comparative SRH) and cause-specific mortality. METHODS: Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of the prevalence and incidence of major age-associated conditions. Data on demographic and health-related variables were collected from 5,278 subjects (≥65 years) in the baseline questionnaire. Thirteen-year mortality and cause of death were obtained from the National Death Registry. Adjusted hazard ratios (aHR) for SRH and all-cause and cause-specific mortality were estimated by Cox proportional hazard models. RESULTS: At baseline, 4,958 participants (93.9%) answered the SRH questionnaire. At the end of follow-up, 2,468 (49.8%) participants had died, of whom 723 (29.2%) died from cardiovascular diseases, 609 (24.7%) from cancer, and 359 (14.5%) from respiratory diseases. Global SRH independently predicted all-cause mortality (aHR for 'poor or very poor' vs. 'very good' category: 1.39; 95% confidence interval (CI): 1.15-1.69). Analysis of cause-specific mortality revealed that global SRH was an independent predictor for death due to respiratory diseases (aHR for 'poor or very poor' vs. 'very good' category: 2.61; 95% CI: 1.55-4.39), whereas age-comparative SRH exhibited a gradient effect on the risk of death due to stroke. Time-comparative SRH provided small additional predictive value. CONCLUSIONS: The predictive ability of SRH for mortality largely differs according to the specific cause of death, with the strongest associations found for respiratory disease and stroke mortality.

Association between cumulative smoking exposure and cognitive decline in non-demented older adults: NEDICES study.

Whether cumulative smoking exposure is associated with cognitive decline among older adults remains unresolved. To address this question, we used data from the Neurological Disorders in Central Spain (NEDICES) cohort study, in which 2624 older adults were evaluated at two-time points separated by three years. A 37-item version of the Mini-Mental State Examination (MMSE-37) was administered at two visits to assess cognitive change. Regarding smoking exposure, we calculated an individual baseline score based on pack-years (i.e., packs of cigarettes smoked per day multiplied by years of smoking) in current and former smokers. Thus, smoking exposure was categorized into tertiles (low: < 19.0, medium: 19.0-47.0, and high: > 47.0). We used multivariable generalized estimating equation models to assess associations between pack-years and smoking status with 37-MMSE total score change from baseline to follow-up. The MMSE-37 total score had a decline of 1.05 points (confidence interval [CI] 95% 0.62 to 1.48) in the lower tertile of pack-years, 1.16 (CI 95% 0.70 to 1.62) in the middle tertile and 1.17 (CI 95% 0.70 to 1.65) in the higher tertile compared to never smokers, after adjusting for several demographic and clinical variables. The same occurred with smoking status, i.e., a decline of 1.33 (CI 95% 0.87 to 1.79) in current smokers and 1.01 (CI 95% 0.63 to 1.40) in former smokers. Our study provides evidence of the cumulative effect of smoking on cognition in older adults. Using a prospective population-based design, we demonstrated that cumulative smoking exposure was associated with cognitive decline in non-demented older adults. More population-based evidence is required to elucidate this association in older adults without dementia.

Is cognitive reserve associated with the prevention of cognitive decline after stroke? A Systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analyses of the effect of socio-behavioral cognitive reserve (CR) proxies on cognitive decline after stroke. METHOD: Three journal search and indexing databases (PubMed, Scopus and Web of Sciences) were crossed to examine the scientific evidence systematically. In addition, meta-analytic techniques, using mixed-effect methods, were carried out to estimate the impact (pooled effect size) of CR proxies on either dementia incidence or cognitive decline after stroke. RESULTS: Twenty-two studies were included in the systematic revision, whereas nineteen of them were eligible for the meta-analysis. The findings showed that high education is associated with a decreased rate of post-stroke dementia. Moreover, other CR proxies (e.g., occupation, bilingualism or social interaction) demonstrate a protective effect against non-dementia cognitive decline after stroke, although some inconsistencies were found in the literature. Regarding the meta-analysis, occupational attainment and education) showed a protective effect against post-stroke cognitive impairment diagnosis in comparison with a mixed category of different CR proxies. Second, a main cognitive change effect was found, pointing to greater cognitive change after stroke in those with low vs. high CR. CONCLUSIONS: Our findings emphasize that CR may prevent cognitive decline after stroke, but this effect can be modulated by different factors such the CR proxy and individual characteristics such as age or type of lesion. The methodological divergences of the studies (i.e., follow-up intervals, cognitive outcomes) need unification to diminish external sources of variability for predicting rates of cognitive decline after stroke.

Infrared spectroscopic analysis of mononuclear leukocytes in peripheral blood from Alzheimer's disease patients.

Peripheral mononuclear leukocytes from Alzheimer's disease (AD) patients were analyzed by infrared spectroscopy and their spectroscopic properties were compared with those from age-matched healthy controls. Two-dimensional correlation analysis of mean spectra measured at various disease stages shows that the protein secondary structure from AD patients involves ß-sheet enrichment and carbonyl intensity increase relative to healthy controls. The area percentages of ß-sheets, which were obtained by using a peak ratio second-derivative spectral treatment, were used for receiver operating characteristic (ROC) analysis to distinguish between patients with AD and age-matched healthy controls. The critical concentration and area under the curve (AUC) were determined by this curve analysis which showed a good performance for this quantitative assay. The results were 90% sensitivity and 90.5% specificity for determinations involving mild and moderate AD patients, and 82.1% sensitivity and 90.5% specificity for determinations involving patients at the three AD stages (mild, moderate, and severe). The AUC was greater than 0.85 in both scenarios. Taken together these results show that healthy controls are distinguished from mild and moderate AD patients better than from patients with severe disease and suggest that this infrared analysis is a promising strategy for AD diagnostics.