Alzheimer Disease: Kaufer D

McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M, Anonymous00346. · Institute for Ageing and Health, University of Newcastle upon Tyne, UK. · Neurology. · Pubmed #16237129 No free full text.

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Cummings JL, Mackell J, Kaufer D. · UCLA Alzheimer Disease Center, UCLA, Los Angeles, CA, USA. · Alzheimers Dement. · Pubmed #18631950 No free full text.

Abstract: BACKGROUND: Behavioral abnormalities and neuropsychiatric symptoms are common manifestations of Alzheimer's disease (AD). Many clinical trials of cholinesterase inhibitors (ChE-Is) and memantine have included behavioral measures as primary or secondary outcomes, and most have observed behavioral benefits in conjunction with treatment. The purpose of this review was to determine the frequency of positive behavioral outcomes in AD clinical trials and clinical reports, to determine the symptoms most responsive to antidementia agents, and to explore factors that correlate with negative outcomes in clinical trials of antidementia agents with regard to behavioral measures. METHODS: We performed a computerized search of randomized clinical trials and open-label studies of ChE-Is and memantine for AD including a behavioral outcome measure. Studies involving 10 or more patients using therapeutic doses of the target agents and including a behavioral measure as a primary or secondary outcome were included in this review. RESULTS: One hundred fifty-seven peer-reviewed articles and 68 publicly presented abstracts were identified in the literature search. Subsequent review established that 15 publications arising from 13 randomized, double-blind, placebo-controlled AD trials met the review inclusion criteria. Positive outcomes on behavioral measures were reported in 8 of 15 publications as a primary or secondary outcome. In most blinded AD clinical trials, behavioral measures were secondary outcomes. Mood symptoms and apathy have most commonly responded to ChE-Is, whereas memantine has been associated with a reduction in irritability and agitation. However, there is substantial variability among trials in terms of behavioral outcomes. Studies that assessed patients with more severe dementia, included patients with less severe behavioral disturbances at baseline, involved institutionalized patients, or were international in scope tended to have negative outcomes. In institutionalized patients there is commonly an improvement in the placebo group that confounds the observation of any drug-placebo difference. CONCLUSIONS: Antidementia agents have been associated with beneficial behavioral outcomes in many randomized clinical trials and open-label studies. Most studies are not designed to test the psychotropic properties of antidementia drugs. Trials with negative behavioral outcomes are most likely to involve patients who are institutionalized and have few behavioral disturbances at baseline. Clinical trials designed to assess behavioral effects of antidementia agents should anticipate these factors.

Small GW, Kaufer D, Mendiondo MS, Quarg P, Spiegel R. · UCLA Neuropsychiatric Institute, Los Angeles, CA 90024-1759, USA. · Int J Clin Pract. · Pubmed #15853867 No free full text.

Abstract: This analysis aimed to assess mini-mental state examination (MMSE) scores in patients with Alzheimer's disease who received rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, for up to 5 years. Rivastigmine data came from two pooled open-label extensions of four 6-month, randomised, placebo-controlled trials. Projections of decline, had the same patients not been treated, were made using a baseline-dependent mathematical model. MMSE data were available for 1998 rivastigmine-treated patients and 657, 298 and 83 were still on treatment at 3, 4 and 5 years, respectively. The mean (+/-SD) baseline MMSE score was 19.3 (+/-4.9). Projected mean scores in model-based untreated patients declined below 10 points on the MMSE at about 3 years, while the mean MMSE score of patients who remained on rivastigmine stayed above 10 points for 5 years.

Kaufer D. · University of Pittsburgh Alzheimer Disease Research Center, Pittsburgh, PA 15213, USA. · Rev Neurol. · Pubmed #12938071 links to  free full text

Abstract: Consensus diagnostic criteria for dementia with Lewy bodies (DLB) proposed in 1996 have provided a useful foundation for research in the field. As a clinicopathologically defined entity, DLB has overlapping features of both Alzheimer s disease (AD) and Parkinson's disease (PD). Consensus criteria for DLB distinguish it from PD dementia by the earlier appearance of motor signs in the latter. Studies evaluating the standardized clinical diagnostic criteria for DLB have generally found them to be highly predictive of Lewy body pathology. However, many cases with Lewy body pathology and concomitant pathological features of AD elude clinical detection. Emerging data suggests that AD pathological features mask the clinical expression of concomitant Lewy body pathology, and that DLB and PD dementia may be more similar than distinct.

Bohnen N, Kaufer D, Hendrickson R, Ivanco L, Moore R, DeKosky S. · No affiliation provided · J Clin Psychopharmacol. · Pubmed #15118497 No free full text.

This publication has no abstract.

Kaufer D. · Departamento de Nuerología. Escuela de Medicina de la Universidad de Pittsburg, Pennsyvania, EE.UU. · Rev Neurol. · Pubmed #12436383 links to  free full text

Abstract: The overall goal of all therapeutic interventions in Alzheimer s disease (AD) is the optimisation of the adaptive functions and quality of life of these patients. The general strategy for the use of pharmacological interventions in the treatment of neuropsychiatric manifestations of AD includes the following: 1) An exhaustive evaluation of the psychiatric symptomatology; 2) Establish a hierachy of the simptoms to treat based on their severity of symptoms and on their impact on the caregiver; 3) The identification of an adequate agent based on the type of symptoms and subject s characteristics; 4) The initial use of low doses with gradual titration, and 5) Changing one drug at a time. Regarding psychotic symptons, the introduction of new agents (e.g., risperidone) has replaced the use of traditional treatments (e.g., thioridazine) in patients with AD. The presence of psychomotor agitation and aggression can be treated with great variety of drugs, such as antipsychotics, anticonvulsants, antidepressants, and sedatives. Selective serotonine re uptake inhibitors are the treatment of choice for depressive symptomatology. The cholinesterase inhibitors have shown to be useful in the treatment of hallucinations, anxiety and apathy.

Boada M, Cejudo JC, Tàrraga L, López OL, Kaufer D. · Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain. · Neurologia. · Pubmed #12084358 links to  free full text

Abstract: BACKGROUND: The Neuropsychiatric Inventory (NPI) is a validated clinical instrument for the evaluation of psychopathology in dementia. OBJECTIVE: To validate a brief questionnaire form of the NPI (NPI-Q) in Spanish from NPI-Q original version, intended for use in routine clinical practice. PATIENTS AND METHOD: We have developed a crossed validated form between NPI and NPI-Q in 120 Alzheimer's disease patients. RESULTS: Test-retest reliability of the NPI-Q, using Pearson correlation index was r = 0.89 for total symptom scale and r = 0.90 for distress scale. The prevalence of analogous symptom ratings differed by less than 6.7%. Convergent validity between NPI-Q and NPI, using Pearson correlation index was r = 0.879 for total symptom and r = 0.92 for distress scale. CONCLUSIONS: The NPI-Q Spanish version offers the possibility to use a reliable and brief instrument that can be used as a screening in the evaluation of neuropsychiatric symptoms in dementia and associated caregiver distress. It may be suitable for use in general clinical practice and it could be used as a brief neuropsychiatric interview.