Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-β oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-β/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis.

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Regular exercise decreases IL-6 and CRP levels in older persons. The effect of exercise on TNF-α remains unclear.

Background: Most people with dementia live in low- and middle-income countries and little is known about the potential for reducing these numbers by reducing key risk factors. Objective: To investigate the potential for dementia incidence reduction in Brazil, Mozambique, and Portugal (a culturally related, high-income country). Methods: We replicated previously published methods and based on the relative risks from previous studies, we estimated the population-attributable risk (PAR) of dementia in Mozambique, Brazil, and Portugal for seven modifiable risk factors associated with dementia (low educational attainment, physical inactivity, midlife hypertension, midlife obesity, depression, smoking, and diabetes mellitus). The combined PAR was calculated and adjusted for associations between risk factors. The potential for risk factor reduction was assessed by examining the effect of relative reductions of 10% and 20% per decade for each of the risk factors on projections for dementia cases for each decade until 2050. Results: After adjusting for non-independence of risk factors, 24.4%, 32.3%, and 40.1% of dementia cases could be related to seven potentially modifiable risk factors in Mozambique, Brazil, and Portugal, respectively. Reducing the prevalence of each risk factor by 20% per decade could, by 2050, potentially reduce the prevalence of dementia in Mozambique, Brazil, and Portugal by 12.9%, 16.2%, and 19.5%, respectively. Conclusion: There is a substantial difference between the countries in the percentage of dementia cases that could be attributable to the seven potentially modifiable risk factors. The proportion of cases that could be prevented by 2050 if measures were taken to address these main risk factors was higher in Portugal than in Brazil and Mozambique. Each country or region should consider their unique risk factor profile when developing dementia risk reduction programs.

Abstract

Introduction Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high‐income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. Methods We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self‐reported race and country macro‐regions. Results The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. Discussion Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.

Dementia is a global socio-medical problem. The steepest increase in prevalence occurs in Latin-America and Asia. European governments have implemented dementia plans to improve care. We describe common goals of European dementia plans and discuss the Brazilian situation. Sixteen European countries have governmental dementia plans, another four are set to launch them. These plans have some common goals: to raise general awareness on dementia and reduce stigma, to establish more diagnostic centers and increase the number of people with correct diagnoses, to provide integrated care that improves quality of care and quality of life, and to promote educational programs for family and professional carers. European dementia plans have contributed toward raising awareness about dementia. More reference centers for diagnostic evaluations have been established and successful educational programs have been run. Integrated care is still a challenge in most countries. Brazil needs a plan. Facilitators and barriers for implementation should be identified by studying the European plans.

Objective: To translate, establish the diagnostic accuracy, and standardize the Brazilian Portuguese version of the European Cross-Cultural Neuropsychological Test Battery (CNTB) considering schooling level. Methods: We first completed an English-Brazilian Portuguese translation and back-translation of the CNTB. A total of 135 subjects aged over 60 years-65 cognitively healthy (mean 72.83, SD = 7.71; mean education 9.42, SD = 7.69; illiterate = 25.8%) and 70 with Alzheimer's disease (AD) (mean 78.87, SD = 7.09; mean education 7.62, SD = 5.13; illiterate = 10%)-completed an interview and were screened for depression. The receiver operating characteristic (ROC) analysis was used to verify the accuracy of each CNTB test to separate AD from healthy controls in participants with low levels of education (p 4 years of schooling) and high levels of education (X 8 years of schooling). The optimal cutoff score was determined for each test. Results: The Recall of Pictures Test (RPT)-delayed recall and the Enhanced Cued Recall (ECR) had the highest power to separate AD from controls. The tests with the least impact from schooling were the Rowland Universal Dementia Assessment Scale (RUDAS), supermarket fluency, RPT naming, delayed recall and recognition, and ECR. Conclusions: The Brazilian Portuguese version of the CNTB was well comprehended by the participants. The cognitive tests that best discriminated patients with AD from controls in lower and higher schooling participants were RPT delayed recall and ECR, both of which evaluate memory.