Alzheimer Disease: Walker MP

Walker MP, Ayre GA, Perry EK, Wesnes K, McKeith IG, Tovee M, Edwardson JA, Ballard CG. · MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK. · Dement Geriatr Cogn Disord. · Pubmed #11044778 No free full text.

Abstract: Fluctuating cognition (FC) is a common and important symptom in dementia, particularly dementia with Lewy bodies (DLB), although it has not been empirically quantified or characterised. Forty subjects (15 DLB, 15 AD, 10 elderly controls) were evaluated using a clinical FC severity scale, as well as receiving measures of variability in attentional performance and slow EEG rhythms across 90 s, 1 h and 1 week. DLB patients had significantly more severe FC and more severe variability in attentional and slow electrocortical measures than either AD patients or normal controls in all time frames. Attentional and EEG variability also correlated significantly with independent clinical ratings of FC. Clinical quantification and measures of attention and EEG variability can therefore make an important and standardised contribution to the assessment of FC in dementia, facilitating future treatment studies with important implications for the potential causative mechanisms and differential diagnosis.

Walker MP, Ayre GA, Cummings JL, Wesnes K, McKeith IG, O'Brien JT, Ballard CG. · Medical Research Council Neurochemical Pathology Unit, Institute for the Health of the Elderly, Newcastle, UK. · Neurology. · Pubmed #10762503 No free full text.

Abstract: BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. Method:- A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.

Singleton AB, Wharton A, O'Brien KK, Walker MP, McKeith IG, Ballard CG, O'Brien J, Perry RH, Ince PG, Edwardson JA, Morris CM. · Medical Research Council/University of Newcastle upon Tyne, Centre Development in Clinical Brain Ageing, MRC Building, Newcastle upon Tyne, UK. · Dement Geriatr Cogn Disord. · Pubmed #12411758 No free full text.

Abstract: Dementia with Lewy bodies (DLB) represents the second commonest cause of dementia in the elderly following Alzheimer's disease (AD). Whilst the presence of Lewy bodies is essential, DLB shares with AD the presence of senile plaques (SP), but neurofibrillary tangles (NFT) are not a necessary feature. The apolipoprotein E (APO E) epsilon4 allele is the most consistently associated genetic risk factor for AD and has also been shown to associate with DLB. We have therefore analysed the APO E epsilon4 allele in a large series of DLB cases coming to autopsy to: (1) determine if the epsilon4 allele describes a similar risk in DLB development as in AD and (2) determine how APO E epsilon4 allele status correlates with clinical and neuropathological findings in DLB, and in AD, as an indication of the role of APO E in underlying disease biology. Both DLB and AD share an increased epsilon4 allele frequency, though in DLB the epsilon2 allele frequency is not reduced and there is a relative lack of epsilon4 homozygotes. In contrast to previous studies, no association of the epsilon4 allele with age at onset or duration of disease was found in either disorders. In DLB cases, overall a significantly shorter duration of illness was observed when compared with AD cases, though no significant effect of the epsilon4 allele on disease onset or duration was seen. The survival rate was reduced by the presence of the epsilon4 allele in DLB, as with AD. No effect on SP or NFT counts was seen with the epsilon4 allele, though DLB cases showed a lower SP burden in addition to the expected lower NFT counts. This study demonstrates that DLB shares the APO epsilon4 allele with AD as a common risk factor, but that there are differences in the way the epsilon4 allele affects the phenotypic expression of disease.

Grace JB, Walker MP, McKeith IG. · Lecturer in Psychiatry, Department of Old Age Psychiatry, Wolfson Research Unit, Newcastle General Hospital, Newcastle upon Tyne, UK. · Int J Geriatr Psychiatry. · Pubmed #11113983 No free full text.

Abstract: INTRODUCTION: Sleep disturbances are common in healthy old age and in dementia syndromes. Polysomnography has demonstrated typical changes in both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) with AD being characterised by sundowning and sleep apnoea and DLB patients showing more disturbances of movement control during sleep. The technical difficulties associated with EEG sleep recordings mean that polysomnography is not possible out of specialist centres. OBJECTIVES: To use questionnaires to assess the frequency of sleep disturbances in patients with Alzheimer's disease and dementia with Lewy bodies. METHOD: The sleep profiles of twenty patients with AD and 17 with DLB were assessed using three questionnaires, one designed to assess night time sleep disturbance, one day time sleepiness and the last carer burden. The sleep questionnaires were repeated in a subgroup after treatment with a cholinesterase inhibitor (rivastigmine). RESULTS: Level of sleep disturbance in both groups was high. DLB patients had more overall sleep disturbance, more movement disorders whilst asleep and more abnormal day time sleepiness. Treatment with rivastigmine produced a trend towards normalisation of sleep profile in a small number of subjects. CONCLUSIONS: Both groups have extensive sleep problems. The DLB and AD groups have different sleep profiles that are of diagnostic importance and may suggest different treatment strategies. The results are consistent with those found from polysomnographic assessment and suggest that the questionnaires used are sensitive to detect differences previously documented with polysomnography.