K. Wesnes

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer’s disease, and vascular dementia

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.

Impaired attention predicts falling in Parkinson's disease

BACKGROUND Cognitive deficits, in particular deficits of attention and executive function, may affect postural sway and balance in Parkinsons disease (PD). Our objective was to determine whether measures of attention were associated with falls in a large cohort of subjects with PD studied prospectively. METHODS Patients meeting UK PD Society Brain Bank Criteria were included. Assessment included UPDRS III and the Cognitive Drug Research computerised assessment battery (CDR) from which Power of Attention, Continuity of Attention, cognitive reaction time and reaction time variability were derived. Falls were assessed prospectively using monthly fall diaries returned over a year following baseline assessment. RESULTS One hundred and sixty four subjects completed fall diary datasets. One hundred and three (63%) fell one or more times during the 12 month period. Regression analysis revealed an association of fall frequency with poorer Power of Attention and increased reaction time variability, which was retained after correcting for UPDRS scores. CONCLUSIONS Reduced power of attention and increased reaction time variability are associated with increased fall frequency in PD. This has implications for the identification of those most at risk of falling, and for the management and prevention of falls in this patient group.

Effect of levodopa on cognitive function in Parkinson’s disease with and without dementia and dementia with Lewy bodies

Background: Levodopa (L-dopa) is the gold standard treatment for Parkinson’s disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unclear. Aim: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson’s disease. Method: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson’s disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard “bedside” measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. Results: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson’s disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson’s disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. Conclusion: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.

Regulation of attention and response to therapy in dementia by butyrylcholinesterase.

OBJECTIVES To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. METHODS We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. CONCLUSIONS These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.

Quantification and Characterisation of Fluctuating Cognition in Dementia with Lewy Bodies and Alzheimer’s Disease

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.

Association between mild vascular cognitive impairment and impaired activities of daily living in older stroke survivors without dementia.

Objectives: To determine the relationship between mild vascular cognitive impairment (mVCI) and functional disability in older stroke survivors without dementia.

Subtle Attentional Deficits in the Absence of Dementia Are Associated with an Increased Risk of Post-Operative Delirium

Background: Previously, key studies of the risk profile for post-surgical delirium have focused on general medical and non-elective patients, few have examined elective cohorts. Accurate prediction is imperative for clinical trials and prevention strategies. Aims/Hypothesis: Our hypothesis was that subtle pre-operative impairments of attention will be associated with risk of post-operative delirium. Method: A prospective study evaluating pre- and post-operative neuropsychological performance in older (≧70) consecutive elective admissions for orthopaedic surgery, and free of dementia (n = 100) was initiated in a general medical hospital. Results: Pre-operative attentional deficits were closely associated with delirium. Patients who developed post-surgical delirium had significantly slower mean reaction times (p ≤ 0.011) and greater variability of reaction time (p = 0.017). A 4- to 5-fold increased risk of delirium was observed for people one standard deviation above the sample means on these variables. Conclusions: The present study describes a measurement of attentional performance which could form the basis of a neuropsychological marker of delirium.

A Psychophysiological Investigation of Fluctuating Consciousness in Neurodegenerative Dementias

Fluctuating levels of consciousness (FC) are a key feature in neurodegenerative dementias, yet clinical identification is poor, hindering accurate diagnosis. One hundred and nineteen patients (32 Dementia with Lewy Bodies (DLB), 57 Alzheimers disease (AD) and 30 controls) with clinical scores of FC were assessed using an attentional task. Cortical arousal was assessed in 25 of these patients using electroencephalography. Over 90 s both variability in attention (p<0·0001) and fluctuations in electrocortical activity (p<0·0001) correlated with clinical FC scores, and with each other (p<0·0001). Variability in attention and electrocortical arousal are accurate FC markers and can assist differential diagnosis of AD and DLB. Previous work has underestimated the intensity and hence impact of FC in dementia. Copyright