Laiss Bertola

Clinical Applicability and Cutoff Values for an Unstructured Neuropsychological Assessment Protocol for Older Adults with Low Formal Education

Background and Objectives The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. Methods and Results A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. Conclusion The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer's disease, mild cognitive impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment—subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI)—and patients with Alzheimers disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGA). The individuals were compared when divided in three (NC—MCI—AD) and four (NC—aMCI—a+mdMCI—AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Development, validity, and reliability of the General Activities of Daily Living Scale: a multidimensional measure of activities of daily living for older people

OBJECTIVE To propose and evaluate the psychometric properties of a multidimensional measure of activities of daily living (ADLs) based on the Katz and Lawton indices for Alzheimers disease (AD) and mild cognitive impairment (MCI). METHODS In this study, 85 patients with MCI and 93 with AD, stratified by age (≤ 74 years, > 74 years), completed the Mini Mental State Examination (MMSE) and the Geriatric Depression Scale, and their caregivers completed scales for ADLs. Construct validity (factor analysis), reliability (internal consistency), and criterion-related validity (receiver operating characteristic analysis and logistic regression) were assessed. RESULTS Three factors of ADL (self-care, domestic activities, and complex activities) were identified and used for item reorganization and for the creation of a new inventory, called the General Activities of Daily Living Scale (GADL). The components showed good internal consistency (> 0.800) and moderate (younger participants) or high (older participants) accuracy for the distinction between MCI and AD. An additive effect was found between the GADL complex ADLs and global ADLs with the MMSE for the correct classification of younger patients. CONCLUSION The GADL showed evidence of validity and reliability for the Brazilian elderly population. It may also play an important role in the differential diagnosis of MCI and AD.

Evaluating Language Comprehension in Alzheimer's disease: the use of the Token Test

OBJECTIVE To analyze the psychometric properties of the Token test (TT), a verbal comprehension test, and its applicability to the diagnosis of mild Alzheimers disease (AD). METHODS One hundred and sixty participants (80 AD and 80 controls) performed the TT and a short battery of neuropsychological tests designed to evaluate general cognitive status, working memory and executive functions. Internal consistency, factor structure, correlation with other measures and group comparisons were evaluated. RESULTS The test evinced good internal consistency and a bi-factorial structure (related to comprehension and attention). Differences between AD and controls were significant, however the TT presented only moderate sensitivity and specificity for the AD diagnosis. CONCLUSION The TT showed evidence of good psychometric properties and adequacy for characterizing comprehension deficits in AD, but it was not an appropriate test for the AD detection and diagnosis.

18F-FDG PET/CT ON THE DIFFERENTIAL DIAGNOSIS BETWEEN MILD COGNITIVE IMPAIRMENT AND MILD ALZHEIMER'S DISEASE

Background: Previous structural and functional MRI studies support the hypothesis that the preclinical state of Alzheimer’s disease is distinct from normal aging. The aim of this study was to use diffusion tensor imaging (DTI) measures in order to determine the existence of white matter microstructural differences in preclinical Alzheimer’s disease subjects. Additional objective was to elucidate whether high cognitive reserve also has an influence on white matter changes, and thus aid preclinical Alzheimer’s disease subjects to tolerate a more advanced stage of white matter degeneration. Methods: Thirty-eight subjects with normal cognition were included. Nineteen were in the preclinical Alzheimer’s disease stage, with decreased cerebrospinal fluid amyloid-b (Ab 42,<500 pg/ml). Nineteen matched participants with normal Ab 42 levels were included as a control group. Fractional anisotropy, radial diffusivity, axial diffusivity and mean diffusivity maps were calculated for each participant using the eigenvalues extracted from the diffusion tensors. Voxel based analyses of DTI measures maps were performed using the Tract Based Spatial Statistics. Results:We encountered increases in axial diffusivity in preclinical Alzheimer’s disease relative to controls in corpus callosum, corona radiata, internal capsule and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Interestingly, we found significant associations between axial diffusivity values and A b 42 levels (not with total tau or phospho-tau); cognitive reserve score was also positively associated with axial diffusivity exclusively in the preclinical Alzheimer’s disease group. The axial diffusivity index presented good sensitivity (84%) and specificity (79%) for discriminating preclinical Alzheimer’s disease from controls (area under the curve: 0.87). Conclusions: The results suggest that early white matter changes in preclinical Alzheimer’s disease can be detected by DTI. The finding of axial diffusivity alteration together with preserved fractional anisotropy and radial diffusivity indexes in the preclinical Alzheimer’s disease group may indicate that A b 42 levels may be associated with subtle axonal changes, while white matter integrity is still widely preserved. In addition, cognitive reserve seems to act as a buffer for these early white matter changes, preserving cognitive functioning in patients with more advanced structural damage.

Verbal fluency in older adults with low educational level: what is the role of executive functions and processing speed?

Neuropsychological tests related to verbal fluency paradigms are among those most frequently used to assess executive functions in older adults. These tasks are quick and easy to administer and widely used for clinical assessment. However, despite their apparent simplicity, these tests involve different cognitive demands and are influenced by sociodemographic factors. Two cognitive domains are particularly related to verbal fluency performance: executive functions and processing speed. Performance on these two cognitive domains declines with age and mediates the effect of other cognitive and demographic factors on verbal fluency scores. The objective of the present report is to investigate the contribution of executive functions and processing speed on category fluency performance. We hypothesize that these two cognitive domains will be related to test performance, suggesting that verbal fluency may not be used as a unidimensional measure of executive functions. Letters to the Editor 440

Oxidative stress markers imbalance in late-life depression

BACKGROUND Oxidative stress has been implicated in the pathophysiology of mood disorders in young adults. However, there is few data to support its role in the elderly. The primary aim of this study was to evaluate whether subjects with late-life depression (LLD) presented with changes in oxidative stress response in comparison with the non-depressed control group. We then explored how oxidative stress markers associated with specific features of LLD, in particular cognitive performance and age of onset of major depressive disorder in these individuals. METHODS We included a convenience sample of 124 individuals, 77 with LLD and 47 non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, and glutathione S-transferase (GST) activity. RESULTS We found that participants with LLD had significantly higher free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity (p = 0.006) compared to controls. Free 8-isoprostane levels were also significantly correlated with worse scores in the initiation/perseverance (r = -0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the total scores (r = -0.21, p = 0.04) on the DRS. CONCLUSIONS Our study provides robust evidence of the imbalance between oxidative stress damage, in particular lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD, and cognitive impairment in this population. Interventions aiming to reduce oxidative stress damage can have a potential neuroprotective effect for LLD subjects.

Assessing knowledge: psychometric properties of the BAMS semantic memory battery

Background: Semantic memory is a cultural influenced cognitive domain that is responsible for our knowledge about words and the world. Semantic Memory Battery (BAMS) is a new battery that evaluate semantic memory based on a compendium of tasks, including verbal fluency, naming, conceptualization, categorization, general questions, and word definitions, and was designed to consider cultural aspects. Objectives: We aimed to evaluate the BAMS psychometrics structure comprising classical and modern analysis, and also evaluate a clinical subdivision of the battery. Methods: 114 Brazilian cognitively healthy older adults BAMS performance provided data for psychometric analysis using validity tests, item response theory analysis and confirmatory factor analysis for goodness-of-fit measures. Results: BAMS results revealed good validity and good-fit measures in each subtest, total score (X2 = 20.684, p = 0.110) and a hierarchical structure with clinical subdivision of the battery (X2 = 20.089, p = 0.093). Discussion: BAMS is a new compendium of tasks that evaluate distinct aspects of semantic memory and can clinically consider the impact of executive function. This battery evaluates verbal fluency, naming, conceptualization, categorization, general knowledge and word definitions. The BAMS has clinical importance once semantic memory is mostly influenced by culture and language, and there is an absence of broadly semantic memory tests in our scenario, especially with older adults that can have a pathological aging condition that affects primarily or secondarily this domain.

EFFECT OF BDNF VAL66MET AND APOE POLYMORPHISM ON COGNITION IN OLDER ADULTS

He initially illustrated the clinical manifestations of progressive nonfluent aphasia in 2011. However, he was finally diagnosed with AD presenting logopenic aphasia in 2013. The follow-up MRI scan showed progression of hippocampal trophy in comparison with the initial image. 3D protein structure modeling revealed that p.Val604Met exchange could result significant changes in the APP protein due to the increased hydrophobicity of methionine in the helix, which could result in alter the APP functions. Conclusions: Further clinical and biochemical studies with genetic analyses of family members would be needed to determine whether these mutations could be involved in AD progression and differentiations.

Functional decline in the elderly with MCI: Cultural adaptation of the ADCS-ADL scale

OBJECTIVE Translate, transcultural adaptation and application to Brazilian Portuguese of the Alzheimers Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale as a cognitive screening instrument. METHOD We applied the back translation added with pretest and bilingual methods. The sample was composed by 95 elderly individuals and their caregivers. Thirty-two (32) participants were diagnosed as mild cognitive impairment (MCI) patients, 33 as Alzheimers disease (AD) patients and 30 were considered as cognitively normal individuals. RESULTS There were only little changes on the scale. The Cronbach alpha coefficient was 0.89. The scores were 72.9 for control group, followed by MCI (65.1) and by AD (55.9), with a p-value < 0.001. The ROC curve value was 0.89. We considered a cut point of 72 and we observed a sensibility of 86.2%, specificity of 70%, positive predictive value of 86.2%, negative predictive value of 70%, positive likelihood ratio of 2.9 and negative likelihood ratio of 0.2. CONCLUSION ADCS-ADL scale presents satisfactory psychometric properties to discriminate between MCI, AD and normal cognition.