Francisco Assis Carvalho Vale

ADAM10 as a Biomarker for Alzheimer’s Disease: A Study with Brazilian Elderly

Alzheimer’s disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis.

ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects.

Abstract ADAM10 is a potential biomarker for Alzheimers disease (AD). ADAM10 protein levels are reduced in platelets of AD patients. The aim was to verify the total blood and platelet ADAM10 gene expression in AD patients and to compare with mild cognitive impairment (MCI) and healthy subjects. No significant differences in ADAM10 gene expression were observed. Therefore, the decrease of ADAM10 protein in platelets of AD patients is not caused by a reduction in ADAM10 mRNA. Further studies must be performed to investigate other pathways in the down regulation of ADAM10 protein.

Subjective memory complaints associated with depression and cognitive impairment in the elderly: A systematic review

The aging process can be accompanied by a slight decline in cognitive functioning, and subjective memory complaints (SMC) appear to be common in the elderly population. Objective To determine whether SMC is associated with cognitive loss or depression and can predict dementia. Methods A systematic review of the literature was conducted. Articles were selected on the following databases, LILACS, SCOPUS, SCiELO, PubMed and Web of Science from August to October 2013. Article selection was based on inclusion and exclusion criteria. Studies published between 2010 and 2013, written in English, Spanish or Portuguese, involving populations 65 years or older, were included. Reviews were excluded. Results After the selection, a summary of the 20 articles retrieved was carried out. Of the total articles retrieved, fifteen were cross-sectional studies and five were longitudinal studies. Most of the cross-sectional studies associated SMC with depression, objective cognitive impairment and anxiety. The emergence of dementia in people with SMC was evidenced in longitudinal studies. Albeit less frequently, SMC were also associated with reduced quality of life, impairment in Activities of Daily Living (ADL), emergence of neuropsychiatric symptoms, lower hippocampal volume, amygdala volume reduction, increased activation of the left temporal, bilateral thalamus, caudate and posterior cingulate, and with the occurrence of ApoE ε4. Conclusion SMC may be associated with changes in mood and/or cognition, and its occurrence appears to increase the likelihood of dementia. In order to further our understanding of the topic, future studies should consider the recruitment of representative samples with control groups and longitudinal designs.

Platelet a disintegrin and metallopeptidase 10 expression correlates with clock drawing test scores in Alzheimer's disease

Earlier studies have demonstrated that a disintegrin and metallopeptidase 10 (ADAM10) levels are reduced in Alzheimers disease (AD) patients compared with healthy subjects. The objective of this study was to evaluate whether platelet ADAM10 levels correlates with the clock drawing test (CDT) scores, which is a simple and a reliable measure of visuospatial ability and executive function in AD patients.

Alzheimer's disease: functional decline and stage of dementia

OBJECTIVE: To determine how Alzheimers disease stage is correlated with the functional ability of elderly people, according to the Functional Independence Measure. METHODS: This observational and cross-sectional study involved elderly people diagnosed with Alzheimers disease and their caregivers. For data collection, the Functional Independence Measure and the Clinical Dementia Rating scale were used. RESULTS: The sample consisted of 67 elderly people (mean age, 79 years). Severe dementia was found in 46.3%, moderate dementia in 22.4%, and mild dementia in 31.3%. The mean scores on the Functional Independence Measure were 107.9, 84.5, and 39.7 for participants with mild, moderate, and severe dementia, respectively. A correlation was found between the Functional Independence Measure and dementia stage (p<0.001). CONCLUSION: The stage of dementia is an important predictive factor for functional performance problems in elderly people with Alzheimers disease.

Correlation Between Mini-Mental State Examination and Platelet ADAM10 Expression in Alzheimer's Disease

BACKGROUND Previous studies have demonstrated a decrease in platelet ADAM10 expression among patients with Alzheimers disease (AD) and healthy matched subjects. The association between cognitive tests and molecular biomarkers, such as platelet ADAM10, may contribute to an accurate AD diagnosis. OBJECTIVE The aim of this research was to investigate whether cognitive deficits in AD, assessed by Mini-Mental State Exam (MMSE), correlate with ADAM10 platelet levels and if that contributes to a more effective AD diagnosis. METHODS Elderly patients with probable AD (n = 30) and a non-AD control group (n = 25), matched by age, gender, and education level were evaluated. Platelet proteins were analyzed on SDS-PAGE (10%) and ADAM10 expression was identified by western blotting. β-actin was used as the endogenous control. The Spearman correlation coefficient between ADAM10 and MMSE ratio was obtained for each group. RESULTS The MMSE ratio of AD subjects (0.45 ± 0.32) was significantly different (p < 0.001) compared to the non-AD group (1.14 ± 0.07). The relationship between MMSE ratio and ADAM10 expression was significant (r = 0.62, p = 0.0003) for the AD group. The combination of ADAM10 and MMSE at a cutoff ≤ 0.87 presented a sensitivity of 85%, and a specificity of 97% (AUC 0.99, 95% CI 0.92 -1.00), which was significantly better for AD diagnosis than the AUCs of MMSE (p = 0.05) and ADAM10 expression (p = 0.18) separately. CONCLUSIONS The association of MMSE and ADAM10 expression was significantly better compared with MMSE and ADAM10 expression separately, thus providing and additional diagnostic tool for AD.

microRNA 221 Targets ADAM10 mRNA and is Downregulated in Alzheimer’s Disease

ADAM10 is the α-secretase that cleaves amyloid-β protein precursor in the non-amyloidogenic pathway in Alzheimers disease (AD) and is known to be regulated by different microRNAs (miRNAs), which are post-transcriptional regulators related to several biological and pathological processes, including AD. Here we proposed to explore and validate miRNAs that have direct or indirect relations to the AD pathophysiology and ADAM10 gene. Approximately 700 miRNAs were analyzed and 21 differentially expressed miRNAs were validated in a sample of 21 AD subjects and 17 cognitively healthy matched controls. SH-SY5Y cells were transfected with miR-144-5p, miR-221, and miR-374 mimics and inhibitors, and ADAM10 protein levels were evaluated. miR-144-5p, miR-221, and miR-374 were downregulated in AD. The overexpression of miR-221 in SH-SY5Y cells resulted in ADAM10 reduction and its inhibition in ADAM10 increased. These findings show that miR-221 can be a new potential therapeutic target for increasing ADAM10 levels in AD. In addition, these results can contribute to the better understanding of ADAM10 post-transcriptional regulation.

The daily life of patients with dementia: A comparative study between the information provided by the caregiver and direct patient assessment

The functionality concept is very important, as the diagnosis of dementia presupposes the existence of functional impairment. Instruments assessing functional performance present some limitations. In most cases, the assessment is based on the caregiver’s report. Some studies in international literature have evaluated this issue and concluded that a difference exists between the caregiver’s report and direct patient assessment. American and European caregivers tend to underestimate the patient’s functional limitations. However, this issue has hitherto not been investigated in our context. Objective To compare the caregiver’s information with direct assessment of the patient’s performance based on the same functional assessment questionnaire. Methods Seventy-two patients and caregivers were attended by the Occupational Therapy service of the Behavioral Neurology Outpatient Clinic between 1999 and 2001, 25 of whom fulfilled the inclusion criteria: having a confirmed diagnosis of dementia according to the DSM-IV; having attended three or more return appointments, and where the caregiver belonged to the patient’s family nucleus. The remaining subjects were excluded because of non-adherence to treatment or refusal to participate in the study. The Functional Activities Questionnaire by Pfeffer et al., 1982 was applied to patients in a laboratory simulation, while another evaluator interviewed the respective caregivers. The data were analyzed based on the weighted Kappa coefficient, and Wilcoxon test. Results There were significative differences between caregiver’s answers and direct observation of the patient’s performance. The information provided by the caregivers proved unreliable since caregivers underestimated the patient’s functional capacity.

Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease

Highlights • Dual tasks can be applicable to assess elderly with mild Alzheimers disease.• Patients with preserved cognition and mild cognitive impairment presented with similar mobility.• Specific local and consequences of falls were identified for each cognitive group.

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study)

UNLABELLED The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. METHOD Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimers Disease (QoL-AD) from baseline to week 24. RESULTS Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. CONCLUSION GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658.