Alzheimer Disease: Kluger A

Reisberg B, Franssen EH, Hasan SM, Monteiro I, Boksay I, Souren LE, Kenowsky S, Auer SR, Elahi S, Kluger A. · Aging and Dementia Research Center, New York University School of Medicine, New York 10016, USA. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #10654097 No free full text.

Abstract: Data from clinical, electrophysiologic, neurophysiologic, neuroimaging and neuropathologic sources indicates that the progression of brain aging and Alzheimer's disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. A word for this process of degenerative developmental recapitulation, "retrogenesis", has been proposed. These retrogenic processes provide new insights into the pathologic mechanism of AD deterioration. An understanding of retrogenic phenonmena can also result in insights into the applicability of retrogenic pathologic mechanisms for non-AD dementing disorders. Management strategies based upon retrogenesis have recently been proposed. Retrogenic pathophysiology also points to previously unexplored pharmacologic approaches to dementia prevention and treatment.

Salloway S, Ferris S, Kluger A, Goldman R, Griesing T, Kumar D, Richardson S, Anonymous00083. · Department of Clinical Neurosciences, Brown University, Providence, RI, USA. · Neurology. · Pubmed #15326237 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). METHODS: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. RESULTS: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. CONCLUSION: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

Myers CE, Kluger A, Golomb J, Gluck MA, Ferris S. · Department of Psychology, Rutgers University. · J Geriatr Psychiatry Neurol. · Pubmed #18474718 No free full text.

Abstract: This study examines whether behavioral measures obtained in nondemented elderly can predict cognitive status at 2-year follow-up. Prior studies have established that delayed paragraph recall can help predict short-term risk for decline to mild cognitive impairment and Alzheimer disease. It was examined whether prediction accuracy can be improved by adding a discrimination-and-generalization task that has previously been shown to be disrupted in nondemented elderly with hippocampal atrophy, a risk factor for Alzheimer disease. Fifty nondemented, medically healthy elderly patients received baseline clinical diagnosis and cognitive testing; 2 years later, patients received a follow-up clinical diagnosis of normal, mild cognitive impairment, or probable Alzheimer disease. In all, 2 baseline variables, delayed paragraph recall and generalization performance, were predictive of follow-up outcome with sensitivity of 81% and specificity of 91%-better than the classification accuracy based on either of these measures alone. These preliminary results suggest that these behavioral tasks may be useful tools in predicting short-term cognitive outcome in nondemented elderly.

Kluger A, Gianutsos JG, Golomb J, Wagner A, Wagner D, Scheurich S. · Department of Psychology, Lehman College/City Universityof New York 10468, USA. · Int Psychogeriatr. · Pubmed #18072982 No free full text.

Abstract: Mild cognitive impairment (MCI) is a classification reserved for nondemented elderly individuals at increased risk for future decline to dementia, compared to those with normal cognition. Cognitive tests, particularly those assessing verbal recall, have been found to be useful in the identification of elderly people with MCI. We argue that a variety of motor/psychomotor evaluations are also sensitive to MCI. Motor assessments described as complex correctly categorize normal versus MCI elderly with comparable accuracies to those obtained by cognitive tests. Unlike performance on verbally based cognitive measures, motor-test scores appear to be relatively independent of educational attainment, indicating that the use of certain motor tests may be particularly valuable in the identification of MCI among elderly with widely varying educational backgrounds.

Reisberg B, Ferris SH, Kluger A, Franssen E, Wegiel J, de Leon MJ. · Aging and Dementia Research Center, New York University School of Medicine, New York 10016, USA. · Int Psychogeriatr. · Pubmed #18031593 No free full text.

Abstract: Descriptions of dementia can be traced to antiquity. Prichard (1837) described four dementia stages and Kral (1962) described a "benign senescent forgetfulness" condition. The American Psychiatric Association's DSM-III (1980) identified an early dementia stage.In 1982, the Clinical Dementia Rating (CDR) and the Global Deterioration Scale (GDS) were published, which identified dementia antecedents. The CDR 0.5 "questionable dementia" stage encompasses both mild dementia and earlier antecedents. GDS stage 3 described a predementia condition termed "mild cognitive decline" or, alternatively, beginning in 1988, "mild cognitive impairment" (MCI). This GDS stage 3 MCI condition is differentiated from both a preceding GDS stage 2, "subjective cognitive impairment" (SCI) stage and a subsequent GDS 4 stage of mild dementia.GDS stage 3 MCI has been well characterized. For example, specific clinical concomitants, mental status and psychological assessment score ranges, behavioral and emotional changes, neuroimaging concomitants, neurological reflex changes, electrophysiological changes, motor and coordination changes, and changes in activities, accompanying GDS stage 3 MCI have been described.Petersen and associates proposed a definition of MCI in 2001 which has been widely used (hereafter referred to as "Petersen's MCI"). Important differences between GDS stage 3 MCI and Petersen's MCI are that, because of denial, GDS stage 3 MCI does not require memory complaints. Also, GDS stage 3 MCI recognizes the occurrence of executive level functional deficits, which Petersen's MCI did not. Nevertheless, longitudinal and other studies indicate essential compatibility between GDS stage 3 MCI and Petersen's MCI duration and outcomes.

Sailor K, Antoine M, Diaz M, Kuslansky G, Kluger A. · Department of Psychology, Lehman College, City University of New York, Bronx, NY 10468-1589, USA. · Neuropsychology. · Pubmed #15099153 No free full text.

Abstract: We collected category fluency data from several moderate-to-large samples of participants at three different sites: the New York University Aging and Dementia Center, the Oregon Health Services Aging and Dementia Research Center, and the Einstein Aging Study at the Albert Einstein College of Medicine. These data were analyzed by calculating the average relative frequency (e.g., typicality) of the category members generated by each participant. Alzheimer's disease (AD) patients recalled fewer atypical members of common taxonomic categories than did the elderly control group. In addition, the probability of producing an item declined at a greater rate for AD patients than for the elderly control group over the duration of the task. According to sequential sampling models, this latter result implies that the rate at which AD patients search memory must be slower than the search rate of the elderly controls.

Reisberg B, Finkel S, Overall J, Schmidt-Gollas N, Kanowski S, Lehfeld H, Hulla F, Sclan SG, Wilms HU, Heininger K, Hindmarch I, Stemmler M, Poon L, Kluger A, Cooler C, Bergener M, Hugonot-Diener L, Robert PH, Antipolis S, Erzigkeit H. · Aging and Dementia Research Center, New York University School of Medicine, New York 10016, USA. · Int Psychogeriatr. · Pubmed #11495392 No free full text.

Abstract: BACKGROUND: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. METHOD: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for > or = 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p <.05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for > or = 12% of variance in the item after controlling for age and gender. RESULTS: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging, .81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). CONCLUSION: This scale can be used to measure therapeutic response in AD.

Golomb J, Wisoff J, Miller DC, Boksay I, Kluger A, Weiner H, Salton J, Graves W. · Silberstein Aging and Dementia Research Center, New York University, University School of Medicine, New York, NY 10016, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #10811706 links to  free full text

Abstract: The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores > or =6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant differences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.

Kluger A, Ferris SH, Golomb J, Mittelman MS, Reisberg B. · Department of Psychiatry, William and Sylvia Silberstein Aging and Dementia Research Center, New York University School of Medicine, New York 10016, USA. · J Geriatr Psychiatry Neurol. · Pubmed #10616864 No free full text.

Abstract: This study examined whether baseline neuropsychological performance in elderly assessed at a research clinic could accurately predict subsequent decline to dementia. Logistic regression analyses were applied to (1) 213 nondemented elderly with a Global Deterioration Scale (GDS) score of 1, 2, or 3, of whom 74 (35%) subsequently declined to any diagnosis of dementia, and (2) a diagnostically more restricted subset of this sample (N = 179), of whom 56 (31%) declined to a diagnosis of probable Alzheimer's disease (AD). The mean follow-up intervals were 3.8 and 3.7 years, respectively. A small set of baseline neuropsychological measures (especially a Paragraph Delayed Recall Test) significantly differentiated decliners from nondecliners to dementia or AD, after accounting for the contribution of age, sex, education, follow-up interval, and the rating of global clinical status. When examined in combination with the other factors or alone, the cognitive tests produced reasonably high specificities (91%-97%) and sensitivities (73%-89%). Using the obtained regression model, a similar level of classification accuracy was replicated on an independent sample of 119 nondemented elderly. A subanalysis of the high-risk GDS 3 subgroup indicated that cut scores from the paragraph test distinguished nondecliners from decliners (overall accuracies 87%-91%), implying that this assessment may accurately predict future cognitive status in elderly with mild cognitive impairment.