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author:("Laks, person")
1.  Integrating Retrogenesis Theory to Alzheimer's Disease Pathology: Insight from DTI-TBSS Investigation of the White Matter Microstructural Integrity 
BioMed Research International  2015;2015:291658.
Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.
PMCID: PMC4320890
2.  The Brazilian version of the Neuropsychiatric Inventory-Clinician rating (NPI-C): Reliability and validity in dementia 
International psychogeriatrics / IPA  2013;25(9):1503-1511.
Patients with dementia may be unable to describe their symptoms, and caregivers frequently suffer emotional burden that can interfere with judgment of the patient's behavior. The Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C) is a comprehensive and versatile instrument to assess neuropsychiatric symptoms (NPS) in dementia. In the NPI-C, the clinician incorporates information from caregiver and patient interviews, and any other relevant available data to accurately measure NPS. The present study is a followup to the original, cross-national NPI-C validation evaluating the reliability and concurrent validity of NPI-C in quantifying psychopathological symptoms in dementia in a large Brazilian cohort.
Two blind raters evaluated 312 participants (156 patient-knowledgeable informant dyads) with the NPI-C totaling 624 observations in 5 Brazilian centers. Inter-rater reliability was determined through calculation of intraclass correlation coefficients for the NPI-C domains and traditional NPI. Convergent validity included correlations of specific domains of the NPI-C with the Brief Psychiatric Rating Scale (BPRS); the Cohen Mansfield Agitation Index (CMAI); the Cornell Scale for Depression in Dementia (CSDD); and the Apathy Inventory (AI).
Inter-rater reliability was strong for all NPI-C domains. There were high correlations between NPI-C/Delusions and BPRS; NPI-C/Apathy-Indifference with the AI; NPI-C/Depression-Dysphoria with the CSDD; NPI-C/Agitation with the CMAI; and NPI-C/Aggression with the CMAI. There was moderate correlation between the NPI-C/Aberrant Vocalizations and CMAI and the NPI-C/Hallucinations with the BPRS.
The NPI-C is a comprehensive tool which provides accurate measurement of NPS in dementia with high concurrent validity and inter-rater reliability in the Brazilian setting. In addition to universal assessment, the NPI-C can be completed by individual domains.
PMCID: PMC3905441  PMID: 23763895
neuropsychiatric symptoms; dementia; Alzheimer's disease; scale; neuropsychiatric assessment
3.  Quality of Life amongst Older Brazilians: A Cross-Cultural Validation of the CASP-19 into Brazilian-Portuguese 
PLoS ONE  2014;9(4):e94289.
As population ageing becomes a global phenomenon the need to understand the quality of life of older people around the world has become increasingly salient. The CASP-19 is a well established measure of quality of later life. The scale is composed of 19 items which map onto the four domains of control (C), Autonomy (A), Self-Realisation (S) and Pleasure (P). It has already been translated to 12 languages and has been used in a number of national and international studies. However use of the scale outside of Europe has been very limited. The objective of this study was to translate and evaluate the use of the CASP-19 amongst older Brazilians.
The CASP-19 was translated from English to Portuguese, back-translated and submitted to an analysis of equivalence by a committee of judges. The scale was then administered to a sample of community dwelling older people in Recife, Brazil (n = 87), and tested for psychometric properties. The Control and Pleasure domains exhibited good internal consistency. By removing one item from each of the Autonomy and Self Realisation domains their internal consistency was improved.
The mean age of the sample was 75.6±0.7 years, subjects were mainly female (52.9%), white (52.9%), who lived without a partner (54%), and had a monthly income varying from USD 340.00 to USD 850.00. Translation and cross-cultural adaptation permitted good understanding and applicability of final version. Psychometric analyses revealed that the removal of two items improved the internal consistency of the Autonomy and Pleasure domains. Confirmatory factor analyses suggest that a 16 item, four factor, model best fits the data.
In this small exploratory study the CASP-19 Brazil demonstrated good psychometric properties. It was easy to use for both participants and researchers. Hopefully future studies in Brazil will employ the scale so that more direct cross national comparisons can be made with older people in Europe and the US.
PMCID: PMC3989195  PMID: 24740240
5.  Different Patterns of White Matter Degeneration Using Multiple Diffusion Indices and Volumetric Data in Mild Cognitive Impairment and Alzheimer Patients 
PLoS ONE  2012;7(12):e52859.
Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.
PMCID: PMC3534120  PMID: 23300797
6.  Factors Associated with a Depressive Disorder in Alzheimer's Disease Are Different from Those Found for Other Dementia Disorders 
This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders.
In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias.
According to the ICD-10 and the DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive disorder. An adjusted multiple regression analysis showed that previous depression (p < 0.05) was significantly associated with depression in AD patients. Severity of dementia (p < 0.05) was significantly associated with a depressive disorder in a group of patients with frontotemporal dementia, vascular dementia, or dementia due to Lewy Body disease or Parkinson's disease.
We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders.
PMCID: PMC3318937  PMID: 22479262
Depression; Dementia; Alzheimer's disease; Inpatients; Institutions
7.  Acute exercise improves cognition in the depressed elderly: the effect of dual-tasks 
Clinics  2011;66(9):1553-1557.
The goal of this study was to assess the acute effect of physical exercise on the cognitive function of depressed elderly patients in a dual-task experiment.
Physical exercise has a positive effect on the brain and may even act as a treatment for major depressive disorder. However, the effects of acute cardiovascular exercise on cognitive function during and after one session of aerobic training in elderly depressive patients are not known.
Ten elderly subjects diagnosed with major depressive disorder performed neuropsychological tests during and after a moderate physical exercise session (65-75%HRmax). A Digit Span Test (Forward and Backward) and a Stroop Color-Word Test were used to assess cognitive function. The elderly participants walked on an electric treadmill for 30 minutes and underwent the same cognitive testing before, during, immediately after, and 15 minutes after the exercise session. In the control session, the same cognitive testing was conducted, but without exercise training.
The results of the Digit Span Test did not change between the control and the exercise sessions. The results of the Stroop Color-Word Test improved after physical exercise, indicating a positive effect of exercise on cognition.
These data suggest that the cognitive functions of depressed elderly persons, especially attention and inhibitory control, are not impaired during and after an acute session of physical exercise. In contrast, the effect of dual-tasks showed beneficial results for these subjects, mainly after exercise. The dual-task may be a safe and useful tool for assessing cognitive function.
PMCID: PMC3164403  PMID: 22179158
Aerobic exercise; Major depression; Attention; Memory; Older
8.  Verbal fluency in Alzheimer's disease, Parkinson's disease, and major depression 
Clinics  2011;66(4):623-627.
To compare verbal fluency among Alzheimer's disease, Parkinson's disease, and major depression and to assess the sociodemographic and clinical factors associated with the disease severity.
Patients from an outpatient university center with a clinical diagnosis of Alzheimer's disease, Parkinson's disease or major depression were studied. Severity was staged using the Hoehn & Yahr scale, the Hamilton Depression scale and the Clinical Dementia Rating for Parkinson's disease, major depression, and Alzheimer's disease, respectively. All subjects were tested with the Mini-Mental State Examination, the digit span test, and the verbal fluency test (animals).
We fit four types of regression models for the count variable: Poisson model, negative binomial model, zero-inflated Poisson model, and zero-inflated negative binomial model.
The mean digit span and verbal fluency scores were lower in patients with Alzheimer's disease (n = 34) than in patients with major depression (n = 52) or Parkinson's disease (n = 17) (p<0.001). The average number of words listed was much lower for Alzheimer's disease patients (7.2 words) compared to the patients presenting with major depression (14.6 words) or Parkinson's disease (15.7 words) (KW test = 32.4; p<0.01). Major depression and Parkinson's disease groups listed 44% (ROM = 1.44) and 48% (ROM = 1.48) more words, respectively, compared to those patients with Alzheimer's disease; these results were independent of age, education, disease severity and attention. Independently of diagnosis, age, and education, severe disease showed a 26% (ROM = 0.74) reduction in the number of words listed when compared to mild cases.
Verbal fluency provides a better characterization of Alzheimer's disease, major depression, and Parkinson's disease, even at later stages.
PMCID: PMC3093793  PMID: 21655757
Verbal fluency; cognition; diagnosis; neuropsychology
9.  LRRK2 p.G2019S Mutation Is Not Common among Alzheimer’s Disease Patients in Brazil 
Disease markers  2009;27(1):13-16.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have emerged as a potential common cause for both sporadic and familial Parkinson’s Disease (PD) in different populations. The pleomorphic features exhibited by LRRK2 mutation carriers and the central role of Lrrk2 protein in the proper functioning of central nervous system suggest that mutations in this protein might be involved in multiple cellular processes leading to other neurodegenerative disorders than PD. The location of LRRK2 gene on chromosome 12, close to a linkage peak for familial late-onset Alzheimer’s Disease (AD), highlights that LRRK2 mutations might be involved in AD pathogenesis. We screened the most common LRRK2 mutation (p.G2019S) in a series of 180 consecutive patients clinically diagnosed with Alzheimer Disease (AD). We identified the p.G2019S in one AD patient with no PD signs, indicating that this mutation is not a common etiological factor for AD in our population (0.5%), corroborating recent data found in Norwegian, North American, Chinese and Italian populations. Nevertheless, these observations together with new information about the Lrrk2 critical multifunctionality do not rule out the possible influence of other variants within LRRK2 in AD, so that other screenings focusing in the whole extension of the LRRK2 using larger sized confirmed AD sample are urgently needed.
PMCID: PMC3835064  PMID: 19822953
Alzheimer’s disease; Leucine-rich repeat kinase 2; LRRK2; p.G2019S mutation; Parkinson’s disease

Results 1-9 (9)