Alzheimer Disease: Acevedo A

Acevedo A, Loewenstein DA. · Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, and Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida 33140, USA. · J Geriatr Psychiatry Neurol. · Pubmed #18004010 No free full text.

Abstract: There have been increasing efforts to develop cognitive interventions to ameliorate cognitive problems experienced by older adults. In healthy elderly populations, cognitive training has centered on the enhancement of memory and speed of processing, with the goal of maximizing current function and reducing the risk of cognitive decline. Among elderly persons with nonprogressive neurological conditions such as traumatic brain injury (TBI) and stroke, there has been an emphasis on rehabilitation to help restore function. Most recently, there has been increased attention on the development of new cognitive techniques to treat persons with progressive neurodegenerative conditions such as Alzheimer disease. The literature is reviewed on current approaches to cognitive interventions in elderly healthy populations, and a particular emphasis is placed on the most recent strides in progressive neurocognitive conditions, particularly Alzheimer disease. Important issues such as study design, the use of ecologically and functionally valid outcome measures, the need to examine heterogeneous populations and cross-cultural variables, and the incorporation of technologically based systems are examined. It is concluded that cognitive interventions in the elderly show considerable promise and deserve further study.

Luis CA, Loewenstein DA, Acevedo A, Barker WW, Duara R. · Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33143, USA. · Neurology. · Pubmed #12939414 No free full text.

Abstract: Mild cognitive impairment (MCI), an intermediate state between normal aging and dementia, is characterized by acquired cognitive deficits, without significant decline in functional activities of daily living. Studies conducted on MCI have introduced new concepts regarding the possible distinctions between normal and pathologic aging of the brain. Neuroimaging and genetic testing have aided in the identification of individuals at increased risk for dementia. The measurement of change in cognitive and functional status in MCI remains challenging, because it requires instruments that are more sensitive and specific than those considered adequate for research in dementia. The authors provide an overview of the many methods that have been used to study MCI and directions that may help achieve greater uniformity in methodology. Considerable heterogeneity exists in research methodology used to study the epidemiology, thresholds for cognitive and functional impairment, rate of progression, risk factors, and defining subtypes of MCI. This article emphasizes the need for uniformity in the use of 1) appropriate and sensitive neuropsychological and functional measures to diagnose MCI, 2) reliable methods to determine progression or improvement of cognitive impairment, and 3) instruments in epidemiologic studies to establish population estimates for diverse ethnic and cultural groups. Greater consensus is needed to standardize definitions and research methodology for MCI, so as to make future studies more comparable and more useful for designing effective treatment strategies.

Loewenstein DA, Acevedo A, Czaja SJ, Duara R. · Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140, USA. · Am J Geriatr Psychiatry. · Pubmed #15249277 No free full text.

Abstract: OBJECTIVE: The authors evaluated the efficacy of a new cognitive rehabilitation program on memory and functional performance of mildly impaired Alzheimer disease (AD) patients receiving a cholinesterase inhibitor. METHODS: Twenty-five participants in the Cognitive Rehabilitation (CR) condition participated in two 45-minute sessions twice per week for 24 total sessions. CR training included face-name association tasks, object recall training, functional tasks (e.g., making change, paying bills), orientation to time and place, visuo-motor speed of processing, and the use of a memory notebook. Nineteen participants in the Mental Stimulation (MS) condition had equivalent therapist contact and number of sessions, which consisted of interactive computer games involving memory, concentration, and problem-solving skills. RESULTS: Compared with the MS condition, participants in CR demonstrated improved performance on tasks that were similar to those used in training. Gains in recall of face-name associations, orientation, cognitive processing speed, and specific functional tasks were present post-intervention and at a 3-month follow-up. CONCLUSION: A systematic program of cognitive rehabilitation can result in maintained improvement in performance on specific cognitive and functional tasks in mildly impaired AD patients.

Loewenstein DA, Ownby R, Schram L, Acevedo A, Rubert M, Argüelles T. · Center for Adult Development and Aging, Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Florida 33140, USA. · J Clin Exp Neuropsychol. · Pubmed #11404806 No free full text.

Abstract: Neuropsychological test batteries are frequently used to assess the nature and severity of cognitive deficits among patients with early Alzheimer's Disease (AD) and related disorders. The NINCDS-ADRDA criteria are among the most widely used guidelines to diagnose dementia (McKhann et al.,1984). These criteria specify eight distinct areas of neuropsychological function that should be evaluated in patients with suspected cognitive impairment. Recent studies have suggested that neuropsychological deficits observed in AD may be explained by a single general factor related to memory deficits or to executive dysfunction. In contrast, the results of other investigations have indicated that multiple qualitatively different factors underlie cognitive abilities in AD. In the present study, we used confirmatory factor analysis to examine the structure of cognitive abilities in AD and to assess the extent to which single and multiple ability factors accurately represent neuropsychological test data obtained from patients with AD. Results indicated that the NINCDS-ADRDA model fit the data better than a single factor model. However, a more parsimonious model specifying memory, verbal abilities, visuospatial skills, executive function, and higher as well as lower functional activities of daily living fit the data better than the NINCDS-ADRDA model. These results have important theoretical and practical implications for diagnostic evaluation.

Acevedo A, Krueger KR, Navarro E, Ortiz F, Manly JJ, Padilla-Vélez MM, Weintraub S, López OL, Mungas D. · Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, MRI Building, 2nd Floor, 4300 Alton Road, Miami Beach, FL 33140, USA. · Alzheimer Dis Assoc Disord. · Pubmed #19474568 No free full text.

Abstract: Researchers from Alzheimer's Disease Centers (ADCs) across the United States with expertise in the assessment of Spanish-speaking elderly collaborated to create the official Spanish version of measures in the Uniform Data Set of the National Institute on Aging Alzheimer's Disease Center Program. The present article describes this project, whose primary goal was to create Spanish instruments with cultural and linguistic equivalence to the English versions. The resulting Spanish versions make provisions for variations among Spanish-speaking groups in the United States of different nationalities, socio-cultural, linguistic, and educational backgrounds. A consensus-based translation and adaptation approach was used, and guiding principles and specific components of this process are summarized. The Spanish translation and adaptation of the Uniform Data Set measures became available online to ADCs in April 2007. Its creation is important, as the resulting effort provides standardized measures for the collection of cross-sectional and longitudinal data on a large cohort of Spanish-speaking elders across the country and facilitates collaborative research among ADCs.

Loewenstein DA, Acevedo A, Agron J, Ownby R, Barker W, Strauman S, Duara R. · Wein Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, USA. · Am J Geriatr Psychiatry. · Pubmed #19390301 No free full text.

Abstract: OBJECTIVE: This study evaluated the utility of the Florida Brief Memory Screen (FBMS), a new memory screening measure developed for Spanish-speaking and English-speaking subjects, which takes only 3-4 minutes to administer. METHODS: The FBMS was administered to 25 patients with probable Alzheimer disease, 23 patients with amnestic mild cognitive impairment, and 80 cognitively normal elderly. RESULTS: The FBMS evidenced good test-retest reliability and high correlation with standard measures of memory. In receiver operating characteristic analyses, the FBMS correctly classified 100% of patients with probable Alzheimer disease and 87.5% of normal elderly subjects. Sensitivity and specificity for patients with amnestic mild cognitive impairment was 82.6% and 87.5%, respectively. Performance on the FBMS was generally independent of the effects of age, education, or primary language. CONCLUSION: The FBMS is a reliable and a valid measure when screening for memory impairment in the elderly and when determining whether a more extensive evaluation is warranted.

Ownby RL, Acevedo A, Harwood DG, Barker WW, Duara R. · Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA. · J Geriatr Psychiatry Neurol. · Pubmed #18287170 No free full text.

Abstract: The purpose of this study was to evaluate whether distinct subtypes of depression could be identified in patients with Alzheimer's disease and, if so, to evaluate the patients in these subgroups. Ratings on the Cornell Scale for Depression in Dementia (CSDD) of 306 patients with Alzheimer's disease, 129 of whom were Spanish- and 177 English-speaking, were subjected to latent class analysis. Four subgroups were identified based on CSDD symptoms. These included an asymptomatic group, groups with mild and more severe typical depression, and a group characterized by prominent anxiety and irritability in addition to sadness. Group differences on demographic, cognitive, clinical, and functional status measures were explored via chi-square tests and analyses of variance. Results show that for some patients with Alzheimer's disease, patterns of symptoms of depression are similar to those in younger adult populations. A distinct subtype may exist, however, with prominent anxiety and irritability.

Salvatierra J, Rosselli M, Acevedo A, Duara R. · Department of Psychology, Charles Schmidt College of Science, Florida Atlantic University, Davie, Florida 33314-7714, USA. · Am J Alzheimers Dis Other Demen. · Pubmed #17606528 No free full text.

Abstract: Studies have demonstrated that in verbal fluency tests, monolinguals with Alzheimer's disease (AD) show greater difficulties retrieving words based on semantic rather than phonemic rules. The present study aimed to determine whether this difficulty was reproduced in both languages of Spanish/English bilinguals with mild to moderate AD whose primary language was Spanish. Performance on semantic and phonemic verbal fluency of 11 bilingual AD patients was compared to the performance of 11 cognitively normal, elderly bilingual individuals matched for gender, age, level of education, and degree of bilingualism. Cognitively normal subjects retrieved significantly more items under the semantic condition compared to the phonemic, whereas the performance of AD patients was similar under both conditions, suggesting greater decline in semantic verbal fluency tests. This pattern was produced in both languages, implying a related semantic decline in both languages. Results from this study should be considered preliminary because of the small sample size.

Loewenstein DA, Acevedo A, Agron J, Martinez G, Duara R. · Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, USA. · J Clin Exp Neuropsychol. · Pubmed #17454350 No free full text.

Abstract: Both amnestic and nonamnestic deficits have been observed in patients with mild cognitive impairment (MCI). Most studies have focused on impairment on single cognitive tests rather than amalgamation of the results of several measures to arrive at a composite impairment index. In this investigation, we examined 20 MCI patients diagnosed as prodromal Alzheimer's disease, AD (mean Mini-Mental State Examination, MMSE = 26.1; SD = 1.7) and determined the extent to which they could be differentiated from 70 normal elderly controls based on composite measures at 1.5-SD and 2.0-SD cutoffs for impairment. At the 1.5-SD cutoff, the median number of memory indices impaired in the MCI-AD group was 5 of 7, whereas at the 2.0-SD cutoff, the median number was 4 of 7. A median of 3 of 7 and 2 of 7 nonmemory indices were impaired at 1.5- and 2.0-SD cutoffs for impairment. Receiver operator characteristics (ROC) analyses indicated that the total number of memory tests impaired at 2.0 SD (sensitivity = 95.0%/specificity = 84.3%) and the composite measure of both impaired memory and nonmemory measures (sensitivity of 85.0%/specificity of 100%) had high levels of discrimination and may have utility as indices of early impairment as well as severity of MCI.

Loewenstein DA, Acevedo A, Ownby R, Agron J, Barker WW, Isaacson R, Strauman S, Duara R. · Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, USA. · Am J Geriatr Psychiatry. · Pubmed #17068313 No free full text.

Abstract: OBJECTIVE: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment. METHODS: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD). RESULTS: On immediate memory for passages, delayed visual reproduction, object memory, and a measure sensitive to semantic interference, 70%-78% of patients with MCI were identified as impaired at 1.5 standard deviations or greater below expected levels. Conditional logistical regression for age-matched samples indicated that consideration of raw scores for these neuropsychologic tests in combination did not significantly change the odds of MCI diagnosis. When impairment relative to the total normal elderly sample was calculated based on one or more impairments at a 1.5 or greater cutoff, specificity fell below acceptable levels when more than three memory measures were considered. CONCLUSION: An array of widely used neuropsychologic measures demonstrated utility in distinguishing patients with MCI-AD from cognitively normal community-dwelling elders. The appropriateness of more or less stringent cutoffs was highly influenced by the number of measures considered. These findings have important implications regarding the choice of cut points for impairment used for the diagnosis of MCI in both research and clinical settings.

Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. · Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Fla 33140, USA. · Arch Gen Psychiatry. · Pubmed #16651510 links to  free full text

Abstract: CONTEXT: A history of depression may increase risk for developing Alzheimer disease (AD) later in life. Clarifying this relation might improve understanding of risk factors for and disease mechanisms in AD. OBJECTIVE: To systematically review and complete a meta-analysis on the relation of depression and AD. DATA SOURCES: We conducted electronic bibliographic searches of MEDLINE, PsychLit, EMBASE, and BIOSIS using search terms sensitive to studies of etiology combined with searches on terms related to depression and AD and reviewed reference lists of articles. STUDY SELECTION: Studies with data contrasting depressed vs nondepressed patients who did and did not later develop AD were included. Studies that related continuous measures of depression and cognitive status were excluded. DATA EXTRACTION: Numerical data were independently extracted by 3 reviewers. They also rated studies on a scale that assessed quality indicators for observational studies. Data on the interval between observation of depression and the diagnosis of AD were collected when available. DATA SYNTHESIS: Meta-analytic evaluation with random-effects models resulted in pooled odds ratios of 2.03 (95% confidence interval, 1.73-2.38) for case-control and of 1.90 (95% confidence interval, 1.55-2.33) for cohort studies. Findings of increased risk were robust to sensitivity analyses. Interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a prodrome, depression may be a risk factor for AD. CONCLUSIONS: A history of depression may confer an increased risk for later developing AD. This relation may reflect an independent risk factor for the disease.

Loewenstein DA, Acevedo A, Agron J, Issacson R, Strauman S, Crocco E, Barker WW, Duara R. · Wein Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Fla, USA. · Dement Geriatr Cogn Disord. · Pubmed #16490966 No free full text.

Abstract: There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.

Ownby RL, Loewenstein DA, Schram L, Acevedo A. · Center on Aging and the Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, Florida 33140, USA. · Int J Geriatr Psychiatry. · Pubmed #15027038 No free full text.

Abstract: BACKGROUND: Understanding the structure of cognitive abilities in Alzheimer's disease (AD) has considerable practical and theoretical importance. Some investigators have argued that a single cognitive process underlies the deficits seen in AD, while others have argued for multiple cognitive processes. As deficits in cognitive abilities may reflect the pathological process or processes occurring in AD, determination of the structure of abilities in AD is important. OBJECTIVES: The purpose of this study was to assess the utility of single and multiple ability factor models in differentiating patients with AD from normals. RESULTS: Findings show that although a single factor model accounts for a large part of the variability of a battery of measures used to differentiate patients and normals, a multiple factor model performed substantially better based on multiple fit criteria. CONCLUSIONS: At least in this sample, a multiple ability factor model of cognitive abilities fit data better than a single factor model in differentiating patients with AD from normals.

Loewenstein DA, Acevedo A, Luis C, Crum T, Barker WW, Duara R. · Department of Psychiatry, Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida 33140, USA. · J Int Neuropsychol Soc. · Pubmed #14751011 No free full text.

Abstract: Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer's disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation.

Loewenstein DA, Acevedo A, Schram L, Ownby R, White G, Mogosky B, Barker WW, Duara R. · Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami Beach, FL 33140, USA. · Am J Geriatr Psychiatry. · Pubmed #12611756 No free full text.

Abstract: OBJECTIVE: The authors evaluated the usefulness and psychometric properties of the Semantic Interference Test (SIT) in patients with mild Alzheimer disease (AD). METHODS: Subjects were first presented with 10 common objects to be learned over three trials. Proactive interference was assessed by having subjects recall 10 new objects that were semantically related to the previous ones. Retroactive interference was assessed by having subjects recall the original 10 objects. RESULTS: Controlling for overall memory impairment, very mildly impaired AD patients demonstrated significantly greater proactive and retroactive interference effects than the normal, community-dwelling comparison group. The proactive score alone and the combined proactive-plus-retroactive score index were more effective than traditional neuropsychological measures of delayed recall in distinguishing between the very mildly impaired AD group and the normal-comparison group. CONCLUSION: The authors discuss the potential usefulness of the SIT in identifying vulnerability to semantic interference in early AD.

Ownby RL, Harwood DG, Acevedo A, Barker W, Duara R. · Department of Psychiatry and Behavioral Sciences, University of Miami, FL, USA. · Am J Geriatr Psychiatry. · Pubmed #11481129 No free full text.

Abstract: The authors assessed the equivalence of the factor structure of the Cornell Scale for Depression in Dementia (CSDD) in samples of Anglo and Hispanic patients with Alzheimer's disease (AD). Comparing the factor structure of the CSDD in these groups helps establish its validity and aids in its clinical interpretation with Hispanic patients. CSDD ratings were first subjected to preliminary exploratory factor analyses; then the factor structure of the CSDD across groups of English- and Spanish-speaking patients was tested using structural equation modeling. Analyses showed overall similarity in the CSDD factor structure for the two groups but also revealed differences in factor content for several items. The authors discuss the relevance of these differences for those using the CSDD with Hispanic AD patients.

Loewenstein DA, Argüelles S, Bravo M, Freeman RQ, Argüelles T, Acevedo A, Eisdorfer C. · Center for Adult Development and Aging and the Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Florida, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #11245361 No free full text.

Abstract: The assessment of functional capacity is essential for the diagnosis of dementia by DSM-IV criteria and has important implications for patient intervention and management. Although ratings of functional disability by family or other proxy informants are widely used by clinicians, there have been concerns and empirical evidence that potential reporter biases may result in either overestimation or underestimation of specific functional deficits. In this study, we compared family members' judgments of the functional abilities of seventy-two patients diagnosed with Alzheimer's disease (AD). These judgments were compared to actual objective functional performance on an array of real-world tasks using the Direct Assessment of Functional Status (DAFS) scale. The results indicate that caregivers were extremely accurate in predicting the functional performance of AD patients who were not impaired during objective evaluation. In contrast, caregivers significantly overestimated the ability of impaired AD patients to tell time, to identify currency, to make change for a purchase, and to utilize eating utensils. Higher patient MMSE scores were associated with caregivers' overestimation of functional capacity, while the degree of caregivers' depressive symptoms, as measured by the CES-D depression scale, was not related to either overestimation or underestimation of patients' functional performance.

Acevedo A, Loewenstein DA, Barker WW, Harwood DG, Luis C, Bravo M, Hurwitz DA, Aguero H, Greenfield L, Duara R. · Cognitive Rehabilitation Program, Horizon Health Corporation, Mount Sinai Medical Center, Miami Beach, Florida, USA. · J Int Neuropsychol Soc. · Pubmed #11105466 No free full text.

Abstract: Category fluency tasks are an important component of neuropsychological assessment, especially when evaluating for dementia syndromes. The growth in the number of Spanish-speaking elderly in the United States has increased the need for appropriate neuropsychological measures and normative data for this population. This study provides norms for English and Spanish speakers, over the age of 50, on 3 frequently used measures of category fluency: animals, vegetables, and fruits. In addition, it examines the impact of age, education, gender, language, and depressed mood on total fluency scores and on scores on each of these fluency measures. A sample of 702 cognitively intact elderly, 424 English speakers, and 278 Spanish speakers, participated in the study. Normative data are provided stratified by language, age, education, and gender. Results evidence that regardless of the primary language of the examinee, age, education, and gender are the strongest predictors of total category fluency scores, with gender being the best predictor of performance after adjusting for age and education. English and Spanish speakers obtained similar scores on animal and fruit fluency, but English speakers generated more vegetable exemplars than Spanish speakers. Results also indicate that different fluency measures are affected by various factors to different degrees.