Alzheimer Disease: Korczyn A

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.

Mayzel-Oreg O, Assaf Y, Gigi A, Ben-Bashat D, Verchovsky R, Mordohovitch M, Graif M, Hendler T, Korczyn A, Cohen Y. · School of Chemistry, The Sackler Faulty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. · J Neurol Sci. · Pubmed #17360001 No free full text.

Abstract: Alzheimer's disease (AD) and Vascular Dementia (VaD) are the most common types of dementia and are progressive diseases affecting millions of people. Despite the high sensitivity of MRI to neurological disorders it has not thus far been found to be specific for the detection of either of these pathologies. In the present study high b-value q-space diffusion-weighted MRI (DWI) was applied to VaD and AD. Controls (N=4), VaD patients (N=8) and AD patients (N=6) were scanned with high b-value DWI, which emphasizes the water component which exhibits restricted diffusion. VaD patients were found to present major WM loss while, in AD, the major pathology found was GM changes, as expected. Also, WM changes in VaD and AD were of a different pattern, more specific to frontal and temporal areas in AD and more widespread in VaD. This pattern of WM changes may be utilized as a diagnosis criterion. Conventional diffusion tensor imaging did not show significant changes between either of the groups and controls. These results demonstrate the potential of high b-value DWI in the diagnosis of dementia.

Werner P, Rosenblum S, Bar-On G, Heinik J, Korczyn A. · Department of Gerontology, University of Haifa, Mt. Carmel, Haifa 31905, Israel. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #16855035 No free full text.

Abstract: This study's aims were (a) to examine kinematically the handwriting process of persons with mild cognitive impairment (MCI), compared with those with mild Alzheimer's disease and healthy controls; (b) to assess the importance of these measures for the differentiation of the groups; and (c) to assess characteristics of the handwriting process across different functional tasks. Thirty-one persons with MCI, 22 with mild Alzheimer's disease, and 41 healthy controls performed functional tasks while using a computerized system. We found significant differences between the groups in almost all measures, with the MCI group assuming a position between the other groups. Temporal measures were higher and pressure was lower in more cognitively deteriorated groups. Information gathered about kinematic measures, together with cognitive functioning, allowed us to classify 69% to 72% of the participants correctly, although the classification for the MCI group was relatively poor.

Farrer LA, Friedland RP, Bowirrat A, Waraska K, Korczyn A, Baldwin CT. · Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. · J Mol Neurosci. · Pubmed #14500999 No free full text.

Abstract: We have found an unusually high prevalence of Alzheimer's disease (AD) in Wadi Ara, an inbred Arab community in northern Israel. Allele frequencies of 4.5% and 3.5% were found for the apolipoprotein E e4 allele among AD cases and nondemented controls, respectively, showing that other genetic or environmental influences must be responsible. Family studies revealed that more than one-third of the AD cases are members of one hamula (tribal group) within Wadi Ara. We hypothesize that the high risk of AD in this genetic isolate may be attributable to a founder effect enhanced by consanguinity. It is also possible that smoking or high fat diet are responsible. To map chromosomal loci contributing to AD susceptibility, we conducted a genome scan from specific hamulas and followed candidate regions found to be linked to disease. Markers from 18 chromosomal regions showed significant allelic association with AD. Smoking was very common in men but was not linked to the presence of AD in Wadi Ara, The unique characteristics of this community, together with the large amount of human genome data, should allow for the identification of AD genes in candidate regions.

Bowirrat A, Friedland RP, Farrer L, Baldwin C, Korczyn A. · Department of Neurology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA. · J Mol Neurosci. · Pubmed #12212789 No free full text.

Abstract: OBJECTIVE: We studied the genetic and environmental risk factors and prevalence, and incidence of dementia of the Alzheimer type (DAT) among the elderly in an Arab community in Israel. BACKGROUND: Epidemiological and genetic studies of dementia have rarely been reported in an Arab population. METHODS: All persons aged 60 years or older who were residents of the rural area of Wadi Ara were examined for identification of DAT, vascular dementia (VaD) and conversion from age related cognitive decline (ARCD) to DAT using DSM-IV criteria and a semi-structured questionnaire for collection of demographic and medical data. ApoE genotype was also determined. Total plasma homocysteine (tHcy) was determined using HPLC with fluorescence detection. Vitamins B12 and plasma folate were determined using a commercial radioisotope dilution kit assay (ICN). RESULTS: DAT was diagnosed in 20.5% of this population. Its prevalence increased steeply with age. Illiteracy was very common, and strongly associated with higher prevalence of DAT. The annual incidence of DAT among ARCD cases was 4.4%. Subjects with ARCD who developed DAT were older than ARCD subjects who did not develop dementia. Hypertension was significantly more common among converted patients than among non-converted. Illiteracy was insignificantly more common among those who developed DAT than among those who remained ARCD. Vascular dementia (VaD) constitutes about 22% of the total dementia population. We also confirm the association between VaD, illiteracy and hypertension. Smoking did not represent a risk factor for VaD. The survival rates among the three groups (healthy subjects, ARCD and DAT) was 80.5%, 58.8% and 55.5% respectively. Homocysteine levels were significantly higher than found in studies in Cleveland. Plasma B12 and plasma folate levels did not differ significantly between DAT patients and controls after adjusting for year of birth. CONCLUSIONS: Our findings suggest that the Wadi Ara population is unique because of high prevalence rates of dementia. We found old age, female gender and lack of education to be risk factors for the development of DAT. The ApoE epsilon4 allele is relatively uncommon in this population and it cannot explain the high DAT prevalence. We also confirm the association between VaD, illiteracy and hypertension and older age and hypertension are risk factors for the transformation of ARCD to DAT.