A H-1 MRS study of probable Alzheimer's disease and normal aging: Implications for longitudinal monitoring of dementia progression

In order to evaluate the capability of H-1 MRS to monitor longitudinal changes in subjects with probable Alzheimer's disease (AD), the temporal stability of the metabolite measures N-acetylaspartate and N-acetylas-partylglutamate (NA), total Creatine (Cr), myo-Inositol (mI), total Choline (Chol), NA/Cr, mI/Cr, Chol/Cr and NA/mI were investigated in a cohort of normal older adults. Only the metabolite measures NA, mi, Cr, NA/Cr, mI/Cr, and NA/mI were found to be stable after a mean interval of 260 days. Relative and absolute metabolite measures from a cohort of patients with probable AD were subsequently compared with data from a sample of normal older adult control subjects, and correlated with mental status and the degree of atrophy in the localized voxel. Concentrations of NA, NA/Cr, and NA/mI were significantly reduced in the AD group with concomitant significant increases in mi and mI/Cr. There were no differences between the two groups in measures of Cr, Chol, or Chol/Cr. Significant correlations between mental status as measured by the Mini-Mental State Examination and NA/mI, mI/Cr and NA were found. These metabolite measures were also significantly correlated with the extent of atrophy (as measured by CSF and GM composition) in the spectroscopy voxel. (C) 1999 Elsevier Science Inc.

The clinical utility of the Hopkins Verbal Learning Test as a screening test for mild dementia

Objective. The purpose of this study was to determine whether the Hopkins Verbal Learning Test (HVLT) could be used as a valid and reliable screening test for mild dementia in older people, and to compare its performance to that of the Mini-Mental State Examination (MMSE). Method. Using a cross-sectional design, we studied three groups of older subjects recruited from a district geriatric psychiatry service: (1) 26 patients with DSM-IV dementia and MMSE scores of 18 or better; (2) 15 patients with psychiatric diagnoses other than dementia; and (3) 15 normal controls. The relationship of each potential cutting point on the HVLT and the MMSE was examined against the independently ascertained DSM-IV diagnoses of dementia using a Receiver Operating Characteristic (ROC) analysis. Results. The subjects consisted of 21 (37.5%) males and 35 (62.5%) females with a mean age of 74.7 (SD 6.1) years and a mean of 8.5 (SD 1.8) years of formal education. ROC analysis indicated that the optimal cutting point for detecting mild dementia in this group of subjects using the HVLT was 18/19 (sensitivity = 0.96, specificity = 0.80) and using the MMSE was 25/26 (sensitivity = 0.88, specificity = 0.93). Conclusions. The HVLT can be recommended as a valid and reliable screening test for mild dementia and as an adjunct in the clinical assessment of older people. The HVLT had better sensitivity than the MMSE in detecting patients with mild dementia, whereas the MMSE had better specificity. Copyright (C) 2000 John Wiley & Sons, Ltd.

Disruptive vocalization and depression in older nursing home residents

Screaming and other types of disruptive vocalization are commonly observed among nursing home residents. Depressive symptoms are also frequently seen in this group, although the relationship between disruptive vocalization and depressive symptoms is unclear. Accordingly, we sought to examine this relationship in older nursing home residents. We undertook a controlled comparison of 41 vocally disruptive nursing home residents and 43 non-vocally-disruptive nursing home residents. All participants were selected to have Mini-Mental State Examination (MMSE) scores of at least 10. Participants had a mean age of 81.0 years (range 63-97 years) and had a mean MMSE score of 17.8 (range 10-29). Nurse ratings of disruptive vocalization according to a semioperationalized definition were validated against the noisy behavior subscale of the Cohen-Mansfield Agitation Inventory. Subjects were independently rated for depressive symptoms by a psychiatrist using the Dementia Mood Assessment Scale, the Cornell Scale for Depression in Dementia, and the Depressive Signs Scale. Vocally disruptive nursing home residents scored significantly higher than controls on each of these three depression-in-dementia scales. These differences remained significant when the effects of possible confounding variables of cognitive impairment, age, and sex were removed. We conclude that depressive symptoms are associated with disruptive vocalization and may have an etiological role in the generation of disruptive vocalization behaviors in elderly nursing home residents.

Stabilization of native protein fold by intein-mediated covalent cyclization

A mutant version of the N-terminal domain of Escherichia coli DnaB helicase was used as a model system to assess the stabilization against unfolding gained by covalent cyclization. Cyclization was achieved in vivo by formation of an amide bond between the N and C termini with the help of a split mini-intein. Linear and circular proteins were constructed to be identical in amino acid sequence. Mutagenesis of Phe102 to Glu rendered the protein monomeric even at high concentration. A difference in free energy of unfolding, DeltaDeltaG, between circular and linear protein of 2.3(+/-0.5) kcal mol(-1) was measured at 10degreesC by circular dichroism. A theoretical estimate of the difference in conformational entropy of linear and circular random chains in a three-dimensional cubic lattice model predicted DeltaDeltaG = 2.3 kcal mol(-1), suggesting that stabilization by protein cyclization is driven by the reduced conformational entropy of the unfolded state. Amide-proton exchange rates measured by NMR spectroscopy and mass spectrometry showed a uniform, approximately tenfold decrease of the exchange rates of the most slowly exchanging amide protons, demonstrating that cyclization globally decreases the unfolding rate of the protein. The amide proton exchange was found to follow EX1 kinetics at near-neutral pH, in agreement with an unusually slow refolding I measured by stopped-flow circular dichroism. rate of less than 4 min(-1) The linear and circular proteins differed more in their unfolding than in their folding rates. Global unfolding of the N-terminal domain of E. coli DnaB is thus promoted strongly by spatial separation of the N and C termini, whereas their proximity is much less important for folding. (C) 2005 Elsevier Ltd. All rights reserved.

Prevalence of Alcohol-Related Problems in an Elderly Population and Their Association With Cognitive Impairment and Dementia

Background: Studies investigating the association between alcohol use and cognitive disorders in the elderly population have produced divergent results. Moreover, the role of alcohol in cognitive dysfunction is not clear. The aims of this study were to estimate the prevalence of alcohol-related problems in an elderly population from Brazil and to investigate their association with cognitive and functional impairment (CFI) and dementia. Methods: A community-based cross-sectional study was performed. A sample of 1,145 elderly people was examined in 2 phases. Several instruments were utilized in the first phase: the CAGE questionnaire was used to identify potential cases of alcohol-related problems, and a screening test for dementia was used to estimate CFI. The CAMDEX interview (Cambridge Examination) and DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria were used for the clinical diagnosis of dementia in the second phase. Results: ""Heavy alcohol use"" (CAGE >= 2) was found in 92 subjects (prevalence: 8.2%). It was associated with gender (males, p < 0.001), low education (only in females, p = 0.002), and low socioeconomic level (p = 0.001, in females; p = 0.002, in males). The Mini Mental State Examination exhibited a nonlinear relationship with alcohol-related problems in females; ""mild-moderate alcohol use"" (CAGE < 2) presented the highest score. A significant association between alcohol-related problems and cognitive dysfunction was found only in females. ""Heavy alcohol use"" was associated with higher CFI and dementia rates compared to ""mild-moderate alcohol use"" (p = 0.003 and p < 0.001, respectively). ""Mild-moderate alcohol use"" had a tendency of association with lower CFI and dementia rates when compared to ""no alcohol use"" (p = 0.063 and 0.050, respectively). Conclusion: Our findings suggest that alcohol use does not have a linear relationship with cognitive decline.

Improving Alzheimer`s Disease Diagnosis with Machine Learning Techniques

There is not a specific test to diagnose Alzheimer`s disease (AD). Its diagnosis should be based upon clinical history, neuropsychological and laboratory tests, neuroimaging and electroencephalography (EEG). Therefore, new approaches are necessary to enable earlier and more accurate diagnosis and to follow treatment results. In this study we used a Machine Learning (ML) technique, named Support Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD patients from controls. As a result, we developed a quantitative EEG (qEEG) processing method for automatic differentiation of patients with AD from normal individuals, as a complement to the diagnosis of probable dementia. We studied EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16 probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4 years. The results obtained from analysis of EEG epochs were accuracy 79.9% and sensitivity 83.2%. The analysis considering the diagnosis of each individual patient reached 87.0% accuracy and 91.7% sensitivity.

Portuguese version of the Delirium Rating Scale-Revised-98: reliability and validity

Objective To assess the validity and the reliability of the Portuguese version of the Delirium Rating Scale-Revised-98 (DRS-R-98). Methods The scale was translated into Portuguese and back-translated into English. After assessing its face validity, five diagnostic groups (n = 64; delirium, depression, dementia, schizophrenia and others) were evaluated by two independent researchers blinded to the diagnosis. Diagnosis and severity of delirium as measured by the DRS-R-98 were compared to clinical diagnosis, Mini-Mental State Exam, Confusion Assessment Method, and Clinical Global Impressions scale (CGI). Results Mean and rnedian DRS-R-98 total scores significantly distinguished delirium from the other groups (p < 0.001). Inter-rater reliability (ICC between 0.9 and 1) and internal consistency (alpha = 0.91) were very high. DRS-R-98 severity scores correlated highly with the CGI. Mean DRS-R-98 severity scores during delirium differed significantly (p < 0.01) from the post-treatment values. The area under the curve established by ROC analysis was 0.99 and using the cut-off Value of 20 the scale showed sensitivity and specificity of 92.6% and 94.6%, respectively. Conclusion The Portuguese version of the DRS-R-98 is a valid and reliable measure of delirium that distinguishes delirium from other disorders and is sensitive to change in delirium severity, which may be of great value for longitudinal studies. Copyright (c) 2007 John Wiley & Sons, Ltd.

Risk factors for post-stroke depression

Objective. To examine possible risk factors in post-stroke depression (PSD) other than site of lesion in the brain Data sources. 191 first-ever stroke patients were examined physically shortly after their stroke and examined psychiatrically and physically 4 months post-stroke. Setting. A geographically defined segment of the metropolitan area of Perth, Western Australia, from which all strokes over a course of 18 months were examined (the Perth Community Stroke Study). Measures. Psychiatric Assessment Schedule, Mini Mental State Examination, Barthel Index, Frenchay Activities Index, physical illness and sociodemographic data were collected. Post-stroke depression (PSD) included both major depression and minor depression (dysthymia without the 2-year time stipulation) according to DSM-III (American Psychiatric Association) criteria. Patients depressed at the time of the stroke were excluded. Patients. 191 first-ever stroke patients, 111M, 80F, 28% had PSD, 17% major and 11% minor depression. Results. Significant associations with PSD at 4 months were major functional impairment, living in a nursing home, being divorced and having a high pre-stroke alcohol intake (M only). There was no significant association with age, sex, social class, cognitive impairment or pre-stroke physical illness. Conclusion. Results favoured the hypothesis that depression in an unselected group of stroke patients is no more common, and of no more specific aetiology, than it is among elderly patients with other physical illness.

Validation of ASHA FACS-Functional Assessment of Communication Skills for Alzheimer Disease Population

This study vas aimed to validate the American Speech-Language-Hearing Association Functional Assessment Of Communication Skills (ASHA FACS) for a Brazilian population. The scale was translated and adapted into Portuguese. Thirty-two patients with mild Alzheimer disease (AD). 25 patients with moderate AD. and 51 elderly without dementia were examined with Mini Mental State Examination, Geriatric Depression Scale. and Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-cog). The ASHA FACS was answered by their relative/caregiver. The scale`s internal consistency. its inter-examiner and intra-examiner`s reproducibility. and scale`s criterion validity were researched by correlation with ADAS-cog,. The sensitivity and specificity Were also researched. Statistical analyses indicated that the ASHA FACS has excellent internal consistency (Cronbach alpha = 0.955), test-retest reliability (interclass correlation coefficient = 0.995; P < 0.001). and inter-examiners (interclass correlation coefficient = 0.998: P < 0.001). It showed excellent criterion validity when correlated with ADAS-cog,. The ASHA FACS scale showed good sensitivity (75.0%) and specificity (82.4%) values once it is an ecologic and broad evaluation. The ASHA FACS Portuguese version is a valid and reliable instrument to verify communication alterations in AD patients and fills an important gap of efficiency indicators for speech language therapy in our country.

Virtual plants - integrating architectural and physiological models

Recent advances in computer technology have made it possible to create virtual plants by simulating the details of structural development of individual plants. Software has been developed that processes plant models expressed in a special purpose mini-language based on the Lindenmayer system formalism. These models can be extended from their architectural basis to capture plant physiology by integrating them with crop models, which estimate biomass production as a consequence of environmental inputs. Through this process, virtual plants will gain the ability to react to broad environmental conditions, while crop models will gain a visualisation component. This integration requires the resolution of the fundamentally different time scales underlying the approaches. Architectural models are usually based on physiological time; each time step encompasses the same amount of development in the plant, without regard to the passage of real time. In contrast, physiological models are based in real time; the amount of development in a time step is dependent on environmental conditions during the period. This paper provides a background on the plant modelling language, then describes how widely-used concepts of thermal time can be implemented to resolve these time scale differences. The process is illustrated using a case study. (C) 1997 Elsevier Science Ltd.

Comparison of nutritional risk screening tools for predicting clinical outcomes in hospitalized patients

Objective: International nutritional screening tools are recommended for screening hospitalized patients for nutritional risk, but no tool has been specifically evaluated in the Brazilian population. The aim of this study was to identify the most appropriate nutritional screening tool for predicting unfavorable clinical outcomes in patients admitted to a Brazilian public university hospital. Methods: The Nutritional Risk Screening 2002 (NRS 2002), Mini-Nutritional Assessment-Short Form (MNA-SF), and Malnutrition Universal Screening Tool (MUST) were administered to 705 patients within 48 h of hospital admission. Tool performance in predicting complications, very long length of hospital stay (LOS), and death was analyzed using receiver operating characteristic curves. Results: NRS 2002, MUST, and MNA-SF identified nutritional risk in 27.9%, 39.6%, and 73.2% of the patients, respectively. NRS 2002 (complications: 0.6531; very long LOS: 0.6508; death: 0.7948) and MNA-SF(complications: 0.6495; very long LOS: 0.6197; death: 0.7583) had largest areas under the ROC curve compared to MUST (complications: 0.6036; very long LOS: 0.6109; death: 0.6363). For elderly patients, NRS 2002 was not significantly different than MNA-SF (P>0.05) for predicting outcomes. Conclusion: Considering current criteria for nutritional risk, NRS 2002 and MNA-SF have similar performance to predict outcomes but NRS 2002 seems to provide a best yield. (C) 2010 Elsevier Inc. All rights reserved.

Subjective memory impairment in a rural population with low education in the Amazon rainforest: an exploratory study

Background: The high prevalence of subjective memory impairment (SMI) in the elderly living in developed countries may be partly dependent on greater demand placed on them by new technologies. As part of a comprehensive study on cognitive impairment in a population living in the Amazon rainforest, we evaluated the prevalence of SMI and investigated the features associated with it. Methods: We evaluated 163 subjects (82 females) with a mean age of 62.3 years (50-94 years), 110 of whom were illiterate, using the answer to a single question ""Do you have memory problems?"" to classify them into groups with or without SMI. The assessment involved application of the Mini-mental State Examination (MMSE), delayed recall from the Brief Cognitive Battery designed for the evaluation of low educated and illiterate individuals, the Patient Questionnaire (PQ) of the Primary Care Evaluation of Mental Disorders (PRIME-MD), and the Happiness Analogical Scale. Results: A very high prevalence of SMI (70%) was observed, exceeding rates reported by similar studies conducted in developed countries. SMI was more frequent in women, whereas age and education did not impact on prevalence. Subjects with SMI had significantly more somatic and psychiatric symptoms on the PQ, as well as lower means on the MMSE, but not on the delayed recall test. Multiple logistic regressions showed that the most important factor associated with the presence of SMI was a high score on the PQ (OR: 3.84, p = 0.011). Conclusion: Psychological and somatic symptoms may be the principal cause of SMI in this population.

RESTORATION OF THE ROTATION CENTER IN MINIMALLY-INVASIVE TOTAL HIP REPLACEMENT

Objective: Our aim was to evaluate the challenges in obtaining a successful restoration of the rotation center as well as a good positioning of the acetabular component when using the minimally-invasive posterior approach for uncemented total hip replacement. Methods: In a comparative non-random prospective study, 64 adult patients underwent elective total hip arthroplasty using the minimally-invasive posterior approach performed by one single surgeon, All patients included in this study had a superior and lateral migration of the rotation center of the hip in comparison to the normal contralateral hip. Patients were excluded from the study if they presented the following: diagnosis of femoral neck fracture, displasic hip types 2, 3 and 4 (Crowe`s classification), osteoarthritis of the contralateral hip. Of the 64 patients in the study, 39 had a radiographic pre-op acetabular size planning equal or less than 50 mm and 25 patients had a radiographic pre-op acetabular size planning equal or more than 52 mm. We considered a good result the following goals: acetabular bend between 35 and 50 degrees, acetabular size according to the pre-op estimative with full contact in the three zones of DeLee-Charnley, a lower medial and vertical positioning of the rotation center in comparison with the pre-op values and a final limb discrepancy lower than 10 mm. Results: A better restoration of the rotation center, as well as, excellent acetabular positioning was found in patients with smaller acetabular size (equal or less than 50), p=0, 04. We must draw attention to two risks when using the minimally-invasive posterior approach: a vertical acetabular position and a lateral position of the acetabular component increasing the risk of a poor contact in the zone 1 due to an insufficient reaming of the medial acetabular host bone. Conclusion: We propose standard surgical approaches in patients with larger anatomical measurements (acetabular planning size more than 50).

Optimizing the CAMCOG test in the screening for mild cognitive impairment and incipient dementia: saving time with relevant domains

Objective: To identify the CAMCOG sub-items that best contribute for the identification of patients with mild cognitive impairment (MCI) and incipient Alzheimer`s disease (AD) in clinical practice. Methods: Cross-sectional assessment of 272 older adults (98 MCI, 82 AD, and 92 controls) with a standardized neuropsychological battery and the CAMCOG schedule. Backward logistic regression analysis with diagnosis (MCI and controls) as dependent variable and the sub-items of the CAMCOG as independent variable was carried out to determine the CAMCOG sub-items that predicted the diagnosis of MCI. Results: Lower scores on Language, Memory, Praxis, and Calculation CAMCOG sub-items were significantly associated with the diagnosis of MCI. A composite score obtained by the sum of these scores significantly discriminated MCI patients from comparison groups. This reduced version of the CAMCOG showed similar diagnostic accuracy than the original schedule for the identification of patients with MCI as compared to controls (AUC = 0.80 +/- 0.03 for the reduced CAMCOG; AUC = 0.79 +/- 0.03 for the original CAMCOG). Conclusion: This reduced version of the CAMCOG had similar diagnostic properties as the original CAMCOG and was faster and easier to administer, rendering it more suitable for the screening of subtle cognitive deficits in general clinical practice. Copyright (C) 2010 John Wiley & Sons, Ltd.

Psychometric characteristics of the Rivermead Behavioural Memory Test (RBMT) as an early detection instrument for dementia and mild cognitive impairment in Brazil

Background: The Rivermead Behavioural Memory Test (RBMT) assesses everyday memory by means of tasks which mimic daily challenges. The objective was to examine the validity of the Brazilian version of the RBMT to detect cognitive decline. Methods: 195 older adults were diagnosed as normal controls (NC) or with mild cognitive impairment (MCI) or Alzheimer`s disease (AD) by a multidisciplinary team, after participants completed clinical and neuropsychological protocols. Results: Cronbach`s alpha was high for the total sample for the RBMT profile (PS) and screening scores (SS) (PS=0.91, SS=0.87) and for the AD group (PS=0.84, SS=0.85), and moderate for the MCI (PS=0.62, SS=0.55)and NC (PS=0.62, SS=0.60) groups. RBMT total scores, Appointment, Pictures, Immediate and Delayed Story, Immediate and Delayed Route, Delayed Message and Date contributed to differentiate NC from MCI. ROC curve analyses indicated high accuracy to differentiate NC from AD patients, and, moderate accuracy to differentiate NC from MCI. Conclusions: The Brazilian version of the RBMT seems to be an appropriate instrument to identify memory decline in Brazilian older adults.