Alzheimer Disease: Emre M

Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B, Anonymous00263. · Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark. · Eur J Neurol. · Pubmed #17222085 No free full text.

Abstract: The aim of this international guideline on dementia was to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with dementia. It covers major aspects of diagnostic evaluation and treatment, with particular emphasis on the type of patient often referred to the specialist physician. The main focus is Alzheimer's disease, but many of the recommendations apply to dementia disorders in general. The task force working group considered and classified evidence from original research reports, meta-analysis, and systematic reviews, published before January 2006. The evidence was classified and consensus recommendations graded according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. The recommendations for clinical diagnosis, blood tests, neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, genetic testing, tissue biopsy, disclosure of diagnosis, treatment of Alzheimer's disease, and counselling and support for caregivers were all revised when compared with the previous EFNS guideline. New recommendations were added for the treatment of vascular dementia, Parkinson's disease dementia, and dementia with Lewy bodies, for monitoring treatment, for treatment of behavioural and psychological symptoms in dementia, and for legal issues. The specialist physician plays an important role together with primary care physicians in the multidisciplinary dementia teams, which have been established throughout Europe. This guideline may contribute to the definition of the role of the specialist physician in providing dementia health care.

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.

Emre M, Cummings JL, Lane RM. · Department of Neurology, Istanbul Faculty of Medicine, Istanbul, Turkey. · J Alzheimers Dis. · Pubmed #17656830 No free full text.

Abstract: Parkinson's disease dementia (PDD) and Alzheimer's disease (AD) are both characterized by cognitive abnormalities, neuropsychiatric symptoms, and cholinergic deficits. We reviewed data from large, placebo-controlled clinical trials conducted with rivastigmine in patients with PDD and AD to evaluate similarities and differences in response to treatment. In placebo groups, AD patients appeared to show more rapid cognitive decline than those with PDD. Treatment effects (rivastigmine versus placebo) on cognitive performance over 6 months were quantitatively similar in both populations, but qualitatively different: in AD, cognitive abilities were stabilized by rivastigmine compared to declines in placebo groups, whereas in PDD symptomatic improvements above baseline drove treatment effects while placebo patients had limited change. On activities of daily living, stabilization (rather than improvement) was observed in both dementia types. A more aggressive course of placebo decline, and greater treatment differences (rivastigmine versus placebo), were seen in sub-populations of both PDD and AD patients with hallucinations at baseline. The safety and adverse event profiles were comparable in the two populations. In conclusion, the magnitude of effect with rivastigmine versus placebo is quantitatively comparable in patients with AD and PD, but the treatment effect tended to be one of stabilization in AD, while in PDD improvements over baseline were seen. In both populations, hallucinations may identify patients who are likely to be more treatment-responsive.

Gauthier S, Emre M, Farlow MR, Bullock R, Grossberg GT, Potkin SG. · McGill Centre for Studies in Aging, Verdun, Quebec, Canada. · Curr Med Res Opin. · Pubmed #14687441 No free full text.

Abstract: Cholinesterase (ChE) inhibitors represent the standard therapeutic approach to the treatment of Alzheimer's disease (AD). However, a proportion of patients experience lack or loss of therapeutic benefit with an initial agent, or discontinue due to safety/tolerability issues. In many instances, no alternative treatment is offered once the initial agent has been stopped. Thus, for many patients, the total duration of treatment is relatively short in comparison with the chronic nature of AD. Switching medications is a common therapeutic strategy within many drug classes across many clinical areas following a lack/loss of efficacy or safety/tolerability problems, and is also an increasingly important concept in the management of AD with ChE inhibitors. A number of open-label studies, where patients were switched from donepezil to rivastigmine, have indicated that approximately 50% of patients experiencing a lack/loss of efficacy with donepezil (a selective acetylcholinesterase [AChE] inhibitor) respond to subsequent treatment with rivastigmine (a dual AChE and butyrylcholinesterase inhibitor). In these studies, rivastigmine was well tolerated, and the occurrence of safety/tolerability problems with donepezil was not predictive of similar problems with rivastigmine. In the summer of 2002, leading neurologists and psychiatrists attended a medical experts meeting to discuss the clinical importance of switching ChE inhibitors in AD. The expert panel examined available clinical data, shared clinical experiences, and discussed current clinical guidelines for switching. The panel also aimed to reach consensus on 'whom to switch', 'when to switch' and 'how to switch'. The key findings from that meeting are reported in this review.

Emre M. · Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul University, Capa Istanbul, Turkey. · Mov Disord. · Pubmed #14502658 No free full text.

Abstract: Parkinson's disease (PD) is frequently associated with mental dysfunction. Domain-specific cognitive deficits are ubiquitous, and although they may not be clinically apparent in all patients, they are demonstrable by neuropsychological testing. Dementia is less frequent but is present significantly more in PD patients than in controls, with a cumulative prevalence rate up to 40% and up to six-fold increased incidence. Cognitive impairment mainly involves executive and visuospatial functions; memory is secondarily impaired with relatively preserved recognition. Qualitatively, the neuropsychological profile of dementia encompasses the same type of deficits found in nondemented PD patients. The dementia seen in PD, therefore, can be described as a dysexecutive syndrome combined with visuospatial dysfunction and behavioural symptoms. Dopaminergic, noradrenergic, serotoninergic, and cholinergic deficits have all been described as the underlying neurochemical impairment, but the strongest evidence exists for a cholinergic dysfunction. Involvement of brainstem nuclei, limbic structures, and cerebral cortex have been suggested as the site, and Lewy body (LB) degeneration and Alzheimer-type changes as the type of pathology underlying the mental dysfunction in PD. Although there is still some controversy as to the site and type of pathology, recent evidence suggests that LB-type degeneration in limbic structures and cerebral cortex, with consequent synaptic and cell loss, is the main pathological state associated with dementia in PD.

Emre M. · Istanbul Faculty of Medicine, Department of Neurology, Turkey. · Int J Clin Pract Suppl. · Pubmed #12139369 No free full text.

Abstract: Despite recognition that cholinesterase inhibitors can provide clinical benefits for patients with Alzheimer's disease (AD), the average durations of treatment and beneficial effects are not optimal in all cases. This may be due to disappointing efficacy or poor tolerability of the initial treatment, as well as secondary efficacy failure or adverse effects emerging during the maintenance phase. In such cases, pharmacological differences between available cholinesterase inhibitors provide a good rationale to switch to another drug in the same class. The pharmacological properties of rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase, and donepezil and galantamine, two AChE-selective inhibitors, are reviewed. Rivastigmine is reported to show brain- and brain region-selectivity. Donepezil appeared to be more selective for central than peripheral enzymes in rats. Galantamine and donepezil have also been shown to exert nicotinic receptor allosteric modulation in vitro, while rivastigmine has been shown to increase binding of acetylcholine to nicotinic receptors in the AD brain. Donepezil and galantamine are metabolised by the hepatic CYP450 system, whereas rivastigmine is metabolised by its target enzymes. Several switching studies indicated that a substantial proportion of patients who fail to benefit from treatment with donepezil could draw benefits after being switched to rivastigmine. An immediate switch from donepezil to rivastigmine was reported to be well tolerated and was not associated with cholinergic side effects. A post hoc analysis of a 5-month trial with galantamine showed that patients had similar efficacy outcomes, whether or not they had received prior anticholinesterase therapy, suggesting that a previous failure to respond to another cholinesterase inhibitor did not predict response to galantamine. On the basis of available data it is suggested that patients not tolerating or not responding to one particular cholinesterase inhibitor may still draw benefits upon switching to another.

Emre M, Qizilbash N. · Istanbul Medical School, Department of Neirology, Capa/Istanbul, Turkey. · Expert Opin Investig Drugs. · Pubmed #11281812 No free full text.

Abstract: Treatment of dementia can be divided as symptomatic treatment of cognitive or non-cognitive symptoms and the treatment of underlying pathology. In the last decade the thrust of symptomatic treatment of Alzheimer's disease (AD) has been enhancement of cholinergic transmission. Besides the acetycholinesterase inhibitors (AChE-I) currently in use, cholinergic agonists and enhancers are in development. Other therapeutic approaches directed towards neurotransmitter substitution or modulation include serotoninergic, noradrenergic substances, neuropeptides and those acting via excitatory amino acid receptors, such as ampakines or NMDA antagonists. Introduction of atypical neuroleptics represents the most recent development in the treatment of behavioural symptoms. Efforts to treat the underlying pathology are based on modulation of APP processing in order to decrease the accumulation of beta-amyloid, those to decrease tau hyperphosphorylation, use of nerve growth factors and those based on Apo-E modulation. Potential use of oestrogens and NSAIDs are also under investigation. Recently, vaccination with amyloid-beta peptide has been reported to be effective in an animal model of AD, this putative vaccine is now in clinical trials. Likewise, recent studies suggest that some statins may have a prophylactic effect.

Waldemar G, Dubois B, Emre M, Scheltens P, Tariska P, Rossor M. · Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark. · Eur J Neurol. · Pubmed #10809933 No free full text.

Abstract: In 1998 a task force to develop guidelines for diagnostic evaluation and treatment of dementia was initiated by the European Federation of Neurological Societies (EFNS) scientist panel on dementia. The aims of the task force were to provide evidence-based recommendations and to highlight the role of the neurologist in the management of patients with Alzheimer's disease and other disorders associated with dementia. We based our recommendations on a review of available evidence-based guidelines supplemented with further literature reviews. The recommendations were derived from consensus meetings and relate to individual patient management, as there are inadequate data on the cost-effectiveness of different diagnostic evaluations and treatments for dementia. Their specific applications will depend upon available resources. The particular contributions of the neurologist include: early identification and differential diagnosis of rare and common brain disorders causing cognitive and behavioural symptoms, referral for and interpretation of ancillary investigations, and identification and treatment of vascular and other concurrent diseases. A review of the management of dementia in Europe revealed considerable variation. In some countries neurologists have taken the lead in the management of patients with dementia, while in other countries the neurologist is rarely involved. We recommend that neurologists should have a clear role in the management of dementia in the whole of Europe. They should be involved in the diagnostic evaluation of dementia and facilitate the development of multidisciplinary teams for evaluation and management of patients with cognitive disturbances. The increasing role of neurology in the management of patients with dementia has important implications for training and education.

Dursun E, Gezen-Ak D, Ertan T, Bilgiç B, Gürvit H, Emre M, Eker E, Engin F, Uysal O, Yilmazer S. · Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. · Dement Geriatr Cogn Disord. · Pubmed #19155622 No free full text.

Abstract: BACKGROUND/AIMS: The polymorphism (rs1800587) in the 5'-flanking regulatory region at -889 of the interleukin-1alpha gene has been shown to be associated with inflammatory diseases and Alzheimer's disease (AD). The aim of the current study is to determine whether there is an association between the promoter region polymorphism of the interleukin-1alpha gene and late-onset AD in a cohort of Turkish patients. METHODS: One hundred and four subjects with dementia of the Alzheimer type and 103 age-matched controls were genotyped according to the PCR with confronting two-pair primers method. RESULTS: Although the distribution of genotypes did not significantly differ (p = 0.107), the difference between allelic frequency was nearly significant according to a chi(2) test (p = 0.05) when the controls and patients were compared. CONCLUSION: Our results showed that there is no association between the -889 C/T transition on the interleukin-1alpha gene and late-onset AD in the Turkish population.

Dursun E, Gezen-Ak D, Eker E, Ertan T, Engin F, Hanagasi H, Gürvit H, Emre M, Yilmazer S. · Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. · J Geriatr Psychiatry Neurol. · Pubmed #19017784 No free full text.

Abstract: Presenilin-1 is known to contribute to the pathogenesis of Alzheimer's disease. The association of an intronic polymorphism (rs165932) of the presenilin-1 gene with late-onset Alzheimer's disease has been documented. However, contradicting results have been shown in different populations. The aim of the current study is to determine whether there is an association between the intronic polymorphism of the presenilin-1 gene and late-onset Alzheimer's disease in a cohort of Turkish patients. One hundred and seven participants with dementia of the Alzheimer type and 106 age-matched controls were genotyped according to BamH I restriction site in intron 8 of the presenilin-1 gene. The distribution of genotypes and alleles did not significantly differ according to chi-square test (P = .52, P = .32, respectively), when the control and patients were compared. Consequently, our results showed that the 1/1 genotype does not increase the risk of developing late-onset Alzheimer's disease in the Turkish population.

Parildar-Karpuzoğlu H, Doğru-Abbasoğlu S, Hanagasi HA, Karadağ B, Gürvit H, Emre M, Uysal M. · Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey. · Neurosci Lett. · Pubmed #18672023 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a poorly understood etiology. There is considerable evidence that oxidative stress occurs in AD and increased DNA damage has been found in brain tissues and leukocytes of AD patients. Base excision repair (BER) is the major pathway responsible for removing oxidative DNA damage. Polymorphisms in DNA-repair genes have been associated with the increased risk of several age-related disorders including various types of cancer and could also be related to the etiology of AD. We conducted a case-control study including 91 patients with AD and age- and sex-matched 93 control subjects to examine the role of single nucleotide polymorphisms of BER genes, hOGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC1 (Arg280His and Arg399Gln) as a risk factor for AD. The frequencies of the hOGG1-Ser326Cys, APE1-Asp148Glu and XRCC1-Arg280His and XRCC1-Arg399Gln variant alleles in our control group were 0.23, 0.31, 0.10 and 0.33, respectively. No significant association was observed between the variant alleles of hOGG1-Ser326Cys (OR=1.32, 95% CI=0.83-2.11), APE1-Asp148Glu (OR=1.08, 95% CI=0.70-1.68), XRCC1-Arg280His (OR=0.53, 95% CI=0.24-1.14) and XRCC1-Arg399Gln (OR=1.05, 95% CI=0.68-1.63) and AD. Our results suggest that the polymorphic variants of these BER genes are not independent risk factors for AD.

Emre M, Mecocci P, Stender K. · Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. · J Alzheimers Dis. · Pubmed #18560130 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, constituting the most common cause of dementia. Memantine, an N-methyl-D-aspartate receptor antagonist indicated for the treatment of moderate to severe AD, has been shown to provide benefits in cognitive, functional, and behavioral domains in large, randomized clinical trials. The current analysis combined data from six previously published studies and assessed the effect of memantine on various cognitive functions in 1826 patients (867 on placebo and 959 on memantine) with moderate to severe AD (MMSE<20). The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and the Severe Impairment Battery (SIB) scores from all six studies were pooled and combined into three clusters representing discrete cognitive domains: language, memory, and praxis. At baseline, there were no clinically significant differences between the memantine- and placebo-treated groups. After 24 weeks, responder analyses revealed that memantine treatment resulted in statistically significantly more patients improving on each of the three clusters, language, memory, and praxis, compared with placebo, and a lower percentage of patients treated with memantine showed any worsening on any of the three clusters compared with patients receiving placebo. It is concluded that treatment with memantine provides benefits in all three cognitive functions.

Gurvit H, Emre M, Tinaz S, Bilgic B, Hanagasi H, Sahin H, Gurol E, Kvaloy JT, Harmanci H. · Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey. · Am J Alzheimers Dis Other Demen. · Pubmed #18276959 No free full text.

Abstract: A cross-sectional, population-based, 2-stage prevalence study was conducted in a sample of 1019 community-dwelling persons over the age of 70 years living in Istanbul. In the first phase, participants were screened with the Mini-Mental State Examination for evidence of cognitive impairment. In the second phase, 79% of those who screened positive (n = 322) and 9% of screen-negatives (n = 63) underwent a standardized diagnostic workup. Diagnosis of dementia and Alzheimer's disease (AD) was made according to established criteria. Ninety-three cases of dementia were identified, 58 of whom were diagnosed with probable AD. Based on these numbers, the prevalence rates of probable AD and dementia were calculated to be 11.0% (95% CI, 7.0% to 15.0%) and 20.0% (95% CI, 14.0% to 26.0%), respectively, in this population. Prevalence rates of dementia and AD in Istanbul, Turkey, are comparable with those seen in the Western world.

Gezen-Ak D, Dursun E, Ertan T, Hanağasi H, Gürvit H, Emre M, Eker E, Oztürk M, Engin F, Yilmazer S. · Istanbul University, Cerrahpasa Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey. · Tohoku J Exp Med. · Pubmed #17592215 links to  free full text

Abstract: Vitamin D(3) is known to be involved in neuroprotection and exert its neuroprotective effects by modulating neuronal calcium homeostasis and production of neurotrophins. The single nucleotide polymorphisms (SNP) in vitamin D receptor (VDR) gene which can influence the affinity of vitamin D(3) to its receptor may be related to neurodegenerative diseases and neuronal damage by altering the vitamin D-mediated pathways. In this study, our aim was to determine whether there is an association between VDR gene and late-onset Alzheimer's disease (AD) in order to see if vitamin D contributes to AD or not. One hundred and four cases of dementia of Alzheimer type and 109 age-matched controls were genotyped according to ApaI (a: + restriction site and A: no restriction site) and TaqI (t: + restriction site and T: no restriction site) sites in intron 8 and exon 9 of the ligand-binding site of VDR gene. When the controls and patients were compared for their ApaI genotypes, the frequency of the patients with Aa genotype was significantly higher than the frequency of the healthy individuals with the same genotype (p = 0.008, chi(2) = 9.577, OR = 2.30). Thus, the "Aa" genotype may increase the risk of developing AD 2.3 times when compared with the "AA" genotype. On the other hand, the "AT" haplotype was significantly higher in controls (p = 0.006) indicating a protective role of the "AT" haplotype in AD. Consequently, this study provides evidence for a possible link between AD and vitamin D.

Doğru-Abbasoğlu S, Aykaç-Toker G, Hanagasi HA, Gürvit H, Emre M, Uysal M. · Department of Biochemistry, Istanbul University, Capa 34093, Istanbul, Turkey. · Neurol Sci. · Pubmed #17385092 No free full text.

Abstract: Alzheimer's disease (AD) is defined pathologically by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically significant (OR=1.95, 95% CI 0.88-4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96-4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the development of AD.

Bronnick K, Emre M, Lane R, Tekin S, Aarsland D. · Norwegian Centre for Movement Disorders, Stavanger University Hospital, Helse Stavanger, Norway. · J Neurol Neurosurg Psychiatry. · Pubmed #17287236 No free full text.

Abstract: OBJECTIVE: To compare the profile of cognitive impairment in Alzheimer's disease (AD) with dementia associated with Parkinson's disease (PDD). METHODS: Neuropsychological assessment was performed in 488 patients with PDD and 488 patients with AD using the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Logistic regression analysis was used to investigate whether the diagnosis could be accurately predicted from the cognitive profile. Additionally, the cognitive profiles were compared with a normative group using standardised effect sizes (Cohen's d). RESULTS: Diagnosis was predicted from the cognitive profile, with an overall accuracy of 74.7%. Poor performance of the AD patients on the orientation test in ADAS-cog best discriminated between the groups, followed by poor performance of the PDD patients on the attentional task in MMSE. Both groups showed memory impairment, AD patients performing worse than PDD patients. CONCLUSION: The cognitive profile in PDD differs significantly from that in AD. Performance on tests of orientation and attention are best in differentiating the groups.

Dogru-Abbasoglu S, Inceoglu M, Parildar-Karpuzoglu H, Hanagasi HA, Karadag B, Gurvit H, Emre M, Aykac-Toker G, Uysal M. · Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey. · Neurosci Lett. · Pubmed #16806697 No free full text.

Abstract: Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing a variety of helix-distorting lesions. Xeroderma pigmentosum group D (XPD) and group F (XPF) are essential participants in NER pathway. There is evidence that two common polymorphisms of XPD gene (g.22541C>A; exon 6 and g.35931A>C; Lys>Gln; exon 23) may be associated with differential DNA repair activities. Alzheimer's disease (AD) is characterized by progressive neuronal loss correlated in time with the symptoms of disease considered. Although deficient DNA repair was proposed in the etiology of AD by several researchers, polymorphisms of DNA repair genes have not been studied in AD yet. We conducted a case-control study including 97 patients with AD and age- and sex-matched 101 control subjects to examine the role of genetic polymorphisms of XPD and XPF (g.30028T>C; exon 11) as a risk factor for AD. The frequencies of the XPD/exon 6, XPD/exon 23, and XPF/exon 11 variant alleles in our control group were 0.41, 0.35, and 0.35, respectively. No significant association was observed between the variant alleles of XPD/exon 6 (OR=0.94, 95% CI=0.63-1.41), XPD/exon 23 (OR=1.24, 95% CI=0.82-1.86) and XPF/exon 11 (OR=1.08, 95% CI=0.72-1.64) and AD. Our results suggest that the polymorphic variants of these NER genes do not contribute to the risk of developing AD.

Sahin HA, Emre M, Ziabreva I, Perry E, Celasun B, Perry R. · Department of Neurology, Ondokuz Mayis University, Faculty of Medicine, Kurupelit, 55139, Samsun, Turkey. · Acta Neuropathol. · Pubmed #16468020 No free full text.

Abstract: We studied the distribution pattern of pathology and cholinergic deficits in the subnuclei of the amygdaloid complex (AC) in five patients with Alzheimer's disease (AD), eight with dementia with Lewy bodies (DLB) and five normal controls. In controls, the basal nucleus contained the highest choline acetyltransferase activity; the activity in the lateral and central nuclei and those in the cortical, medial and accessory basal nuclei were comparable. In AD, there was a significant decrease in choline acetyltransferase activity in the accessory basal and lateral nuclei, in DLB a significant decrease was observed in the accessory basal, lateral and cortical nuclei. Compared to controls the hyperphosphorylated tau-pathology burden was significantly higher in the basal, central and medial nuclei in AD and in the central, cortical, lateral and medial nuclei in DLB. The amyloid plaque burden was significantly higher in the accessory basal, basal, lateral and cortical nuclei in AD and in all nuclei in DLB. The alpha-synuclein burden was significantly higher in all nuclei in both AD and DLB. Compared to AD alpha-synuclein burden was higher in all nuclei in DLB. There were no correlations between the distribution pattern of hyperphosphorylated tau-pathology, amyloid plaques and alpha-synuclein-positive structures, and choline acetyltransferase activity, except the lateral nucleus in DLB. In conclusion we found no relationship between the pattern of cholinergic deficits and the distribution pattern of lesions in the AC of patients with AD or DLB. Cholinergic deficits were more prominent in the nuclei of basolateral (BL) group in AD, whereas the nuclei of both BL and corticomedial groups were involved in DLB, which may be due to the involvement of both basal forebrain and brainstem cholinergic nuclei in the latter.

Sahin HA, Gurvit IH, Emre M, Hanagasi HA, Bilgic B, Harmanci H. · Ondokuz Mayis University, Faculty of Medicine, Department of Neurology, Kurupelit, Samsun, Turkey. · Int Psychogeriatr. · Pubmed #16466587 No free full text.

Abstract: OBJECTIVES: To assess the attitude of elderly lay people towards the concept and symptoms of dementia. METHODS: A population-based, cross-sectional study of 859 residents without dementia, aged 70 years or older, living in an urban area in Istanbul. Nine questions with yes/no responses were designed to investigate the attitudes of the responders to the concept of dementia and symptoms related to particular aspects of dementia. The chi(2)-test was used to test for differences between proportions of respondents in different age, sex and education groups. RESULTS: Dementia was considered as normal by the majority of respondents and age and education did not influence this attitude. Women were significantly less inclined to consider dementia and its associated problems as normal. CONCLUSION: The concept of dementia is generally not considered as a medical problem by the elderly Turkish population, independent of age and education. These results are important in guiding policy makers and shaping awareness raising campaigns of local Alzheimer's Associations.

Boada-Rovira M, Brodaty H, Cras P, Baloyannis S, Emre M, Zhang R, Bahra R, Anonymous00040. · Fundació ACE, Barcelona, Spain. · Drugs Aging. · Pubmed #14715043 No free full text.

Abstract: BACKGROUND: Donepezil has consistently been shown to be effective and well tolerated in the symptomatic treatment of Alzheimer's disease in placebo-controlled clinical trials. It has been shown to provide significant benefits in cognition, global function and activities of daily living in patients with mild-to-moderate Alzheimer's disease. However, in order to control for confounding factors, some clinical trials of donepezil have excluded patients with comorbid illness and concomitant medication use. OBJECTIVE: The objective of this study was to evaluate the efficacy, tolerability and safety of donepezil in a wider and more diverse sample of patients and centres than previous trials, reflecting routine clinical practice. METHODS: In this 12-week, open-label, multicentre trial, patients with probable mild-to-moderate Alzheimer's disease received donepezil 5 mg/day for 28 days, after which the dosage was increased to 10 mg/day according to the investigating clinician's judgement. Patients were enrolled at 246 study centres in 18 countries worldwide. Cognition was assessed by a trained clinician using the Mini-Mental State Examination (MMSE) at baseline, week 4 and week 12 (or last visit). Changes in patient activity and social interaction were evaluated using a caregiver diary. Each week, caregivers recorded their impression of change compared with baseline on three aspects of patient behaviour using a 5-point scale. Efficacy analyses were performed on the intent-to-treat population. Significance was determined using the paired t-test (0.05 significance level). Tolerability and safety were assessed by monitoring adverse events, physical examinations, vital signs, clinical laboratory test abnormalities and ECG findings throughout the study. RESULTS: A total of 1113 patients received donepezil (mean baseline MMSE score [+/-SD] 18.74 +/- 5.21). 989 (88.9%) patients completed the study; 59 (5%) patients discontinued because of adverse events. Most patients were taking at least one concomitant medication (n = 802; 72%) and had at least one comorbid medical condition (n = 745; 67%) on study entry. Donepezil significantly improved cognition compared with baseline at weeks 4 and 12, and at week 12 using a last observation carried forward (LOCF) analysis (all p < 0.0001). Mean change from baseline MMSE score (+/-SE) at week 12-LOCF was +1.73 +/- 0.10. Donepezil was also associated with significant improvements in patient social interaction, engagement and interest, and initiation of pleasurable activities at all weekly assessments and week 12-LOCF (all p < 0.0001). Donepezil was generally well tolerated; adverse events were consistent with the known safety profile of donepezil. CONCLUSION: Donepezil treatment resulted in statistically significant improvements in cognition and patient activity and social behaviour, and was generally well tolerated despite high levels of comorbid illness and concomitant medication use. The results of this open-label study in a large patient population are consistent with those from controlled trials and support that donepezil is effective in the treatment of mild-to-moderate Alzheimer's disease in everyday practice.

Harmanci H, Emre M, Gurvit H, Bilgic B, Hanagasi H, Gurol E, Sahin H, Tinaz S. · Department of Public Health, Marmara University Medical Faculty, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey. · Alzheimer Dis Assoc Disord. · Pubmed #14512826 No free full text.

Abstract: The objective is to study risk factors for Alzheimer disease (AD) in Istanbul, Turkey. This is a population-based case-control study. We screened people over age 70 in the community for cognitive impairment. The screen positives and a proportion of screen negatives underwent neurologic examination in the second phase. Cases were 57 "probable" AD patients and controls were 127 cognitively normal individuals identified by neurologic examination. Odds ratios (OR) were calculated using multivariate logistic regression analysis. Having a university/college degree had a protective effect on AD risk (OR = 0.10, 95% confidence interval [CI] = 0.02-0.50). Exposure to occupational electromagnetic field had an OR of 4.02 (95% CI = 1.02-15.78). Use of electricity for residential heating also showed elevated risk (OR = 2.77, 95% CI = 1.12-6.85). Our results suggest that having a higher education is protective from AD and that electromagnetic field exposure at work or at home is a significant risk factor.

Friedland RP, Emre M, Geula C. · Department of Neurology, CASE School of Medicine, Cleveland, OH 44106, USA. · Amyloid. · Pubmed #17577692 No free full text.

This publication has no abstract.

Geula C, Emre M, Friedland RP. · Laboratory for Neurodegenerative and Aging Research, Department of Medicine, Harvard Medical School,Boston, MA 02215, USA. · Amyloid. · Pubmed #15678765 No free full text.

This publication has no abstract.