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Background: There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages.Objective: The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD.Methods: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD, a Mini-Mental State Examination (MMSE) score ≥22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5.-1.0. The Quality of Life in Alzheimer 's Disease (QoL-AD) questionnaire was used to assess health-related quality of life. A battery of self-report instruments was used to evaluate different psychological and behavioral domains. Associations between the QoL-AD and other outcome measures were analyzed using Spearman's rank correlations.Results: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years and mean disease duration was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1). The mean QoL-AD score was 37.9 (4.5). Eighty-three percent (n = 124) of patients had moderate-to-severe hopelessness, 22.1% (n = 33) had depressive symptoms, and 36.9% (n = 55) felt stigmatized. The quality of life showed a significant positive correlation with self-efficacy and negative correlations with depression, emotional and practical consequences, stigma, and hopelessness.Conclusion: Stigma, depressive symptoms, and hopelessness are frequent scenarios in AD negatively impacting quality of life, even in a population with short disease duration and minimal cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction: Limited information is available on people's experiences of living with Alzheimer's disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures. Methods: We conducted an observational, cross-sectional study in 21 memory clinics in Spain. Persons aged 50–90 years, diagnosed with prodromal or mild AD (NIA/AA criteria), a Mini Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5 or 1.0 were recruited. The Representations and Adjustment to Dementia Index (RADIX) was used to assess participants' beliefs about their condition and its consequences. Results: A total of 149 persons with early-stage AD were studied. Mean (SD) age was 72.3 (7.0) years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a descriptive term related to specific AD symptoms (e.g., memory difficulties) when asked what they called their condition. Participants aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more depressive symptoms, and poorer life satisfaction and quality of life compared to those without awareness of their specific diagnosis. Practical and emotional consequences RADIX scores showed a significant negative correlation with Quality of Life in Alzheimer's Disease score (rho = − 0.389 and − 0.413, respectively; p < 0.0001). Years of education was the only predictor of awareness of AD diagnosis [OR = 1.04 (95% CI 1.00–1.08); p = 0.029]. Conclusions: Awareness of diagnosis was a common phenomenon in persons with early-stage AD negatively impacting their quality of life. Understanding illness representations in earlier stages may facilitate implementing optimized care that supports improved quality of life and well-being. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. (JINS, 2015, 21, 861–867) [ABSTRACT FROM AUTHOR]

Dynamic early-phase PET images acquired with radiotracers binding to fibrillar amyloid-beta (Aβ) have shown to correlate with [18F]fluorodeoxyglucose (FDG) PET images and provide perfusion-like information. Perfusion information of static PET scans acquired during the first minute after radiotracer injection (FMF, first-minute-frame) is compared to [18F]FDG PET images. FMFs of 60 patients acquired with [18F]florbetapir (FBP), [18F]flutemetamol (FMM), and [18F]florbetaben (FBB) are compared to [18F]FDG PET images. Regional standardized uptake value ratios (SUVR) are directly compared and intrapatient Pearson's correlation coefficients are calculated to evaluate the correlation of FMFs to their corresponding [18F]FDG PET images. Additionally, regional interpatient correlations are calculated. The intensity profiles of mean SUVRs among the study cohort (r = 0.98, p < 0.001) and intrapatient analyses show strong correlations between FMFs and [18F]FDG PET images (r = 0.93 ± 0.05). Regional VOI-based analyses also result in high correlation coefficients. The FMF shows similar information to the cerebral metabolic patterns obtained by [18F]FDG PET imaging. Therefore, it could be an alternative to the dynamic imaging of early phase amyloid PET and be used as an additional neurodegeneration biomarker in amyloid PET studies in routine clinical practice while being acquired at the same time as amyloid PET images. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease (AD) amyloid-β (Aβ) deposits may cause impairments in choroid plexus, a specialised brain structure which forms the blood–cerebrospinal fluid (CSF) barrier. We previously carried out a mass proteomic-based study in choroid plexus from AD patients and we found several differentially regulated proteins compared with healthy subjects. One of these proteins, annexin A5, was previously demonstrated implicated in blocking Aβ-induced cytotoxicity in neuronal cell cultures. Here, we investigated the effects of annexin A5 on Aβ toxicity in choroid plexus. We used choroid plexus tissue samples and CSF from mild cognitive impairment (MCI) and AD patients to analyse Aβ accumulation, cell death and annexin A5 levels compared with control subjects. Choroid plexus cell cultures from rats were used to analyse annexin A5 effects on Aβ-induced cytotoxicity. AD choroid plexus exhibited progressive reduction of annexin A5 levels along with progressive increased Aβ accumulation and cell death as disease stage was higher. On the other hand, annexin A5 levels in CSF from patients were found progressively increased as the disease stage increased in severity. In choroid plexus primary cultures, Aβ administration reduced endogenous annexin A5 levels in a time-course dependent manner and simultaneously increased annexin A5 levels in extracellular medium. Annexin A5 addition to choroid plexus cell cultures restored the Aβ-induced impairments on autophagy flux and apoptosis in a calcium-dependent manner. We propose that annexin A5 would exert a protective role in choroid plexus and this protection is lost as Aβ accumulates with the disease progression. Then, brain protection against further toxic insults would be jeopardised. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease. [ABSTRACT FROM AUTHOR]

Kynurenic acid (KYNA) is a product of the tryptophan (TRP) metabolism via the kynurenine pathway (KP). This pathway is activated in neurodegenerative disorders, such as Alzheimer´s disease (AD). KYNA is primarily produced by astrocytes and is considered neuroprotective. Thus, altered KYNA levels may suggest an inflammatory response. Very recently, significant increases in KYNA levels were reported in cerebrospinal fluid (CSF) from AD patients compared with normal controls. In this study, we assessed the accuracy of KYNA in CSF for the classification of patients with AD, cognitively healthy controls, and patients with a variety of other neurodegenerative diseases, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP). Averaged KYNA concentration in CSF was higher in patients with AD when compared with healthy subjects and with all the other differentially diagnosed groups. There were no significant differences in KYNA levels in CSF between any other neurodegenerative groups and controls. These results suggest a specific increase in KYNA concentration in CSF from AD patients not seen in other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]