Parkinson Disease: Kenny RA

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.

Allcock LM, Rowan EN, Steen IN, Wesnes K, Kenny RA, Burn DJ. · Institute for Ageing and Health, Newcastle University, UK. · Parkinsonism Relat Disord. · Pubmed #18487069 No free full text.

Abstract: BACKGROUND: Cognitive deficits, in particular deficits of attention and executive function, may affect postural sway and balance in Parkinson's 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.

Allan LM, Ballard CG, Allen J, Murray A, Davidson AW, McKeith IG, Kenny RA. · Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. · J Neurol Neurosurg Psychiatry. · Pubmed #17178816 No free full text.

Abstract: BACKGROUND: There are no studies of autonomic function comparing Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). AIMS: To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing's battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing's classification. RESULTS: There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p<0.001) and AD (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02). PDD had significantly more impairment than DLB in some autonomic parameters (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02; Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These results were in contrast with AD patients who only showed impairment in one sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls (all p<0.05). CONCLUSION: Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.

Allcock LM, Kenny RA, Burn DJ. · Institute of Ageing and Health, University of Newcastle Upon Tyne, Newcastle Upon Tyne, United Kingdom. · Mov Disord. · Pubmed #16958096 No free full text.

Abstract: The objective of this study was to characterize the phenotypic associations of orthostatic hypotension (OH) in Parkinson's disease (PD). One hundred fifty-nine subjects with PD underwent assessment including autonomic symptom severity scoring, disease-specific rating scales, and measurement of postural blood pressure response. Symptoms of autonomic impairment weakly correlated with disease duration and severity. A posture and gait instability (PIGD) motor phenotype was associated with greater severity of autonomic symptoms. Eighty subjects (50.3%) had OH. These subjects were older, more likely to be male, and taking larger doses of dopaminergic medications than those without OH. There was no difference in disease severity or duration between those with and those without OH. Symptomatic dizziness did not distinguish between groups, although subjects with OH had more symptoms of generalized autonomic impairment than those without. Progressive autonomic involvement may be linked to disease progression in PD, particularly in patients with a PIGD phenotype, but dichotomization into groups with and without OH is a relatively insensitive method for demonstrating this. Longitudinal studies of changes in autonomic reflex abnormalities, autonomic symptom profiles, and motor severity might clarify these associations.

Allcock LM, Kenny RA, Mosimann UP, Tordoff S, Wesnes KA, Hildreth AJ, Burn DJ. · Parkinson's Disease Research Unit, Department of Neurology, Sunderland Royal Hospital, Sunderland, UK. · Int J Geriatr Psychiatry. · Pubmed #16906622 No free full text.

Abstract: BACKGROUND: Orthostatic hypotension is common in Lewy body disorders and may be related to disease progression and the spread of Lewy body pathology. We therefore hypothesize that PD patients with orthostatic hypotension (OH) have a different cognitive profile compared to PD patients without OH. METHODS: This cross-sectional study included 175 PD patients. Blood pressure (BP) was measured with a validated digital blood pressure monitor and patients with a systolic BP drop of > or =20 mmHg or a systolic pressure of <90 mm Hg after standing were considered to have OH. Cognition was assessed using MMSE extended by a selection of computerized cognitive tests focusing on reaction time, sustained attention, working memory and episodic verbal and visual memory. RESULTS: Eighty-seven (49.7%) of the PD patients had OH. These patients were significantly more impaired in sustained attention and visual episodic memory compared to PD patients without OH. CONCLUSION: We conclude that there are differences in the neuropsychological performance of patients with PD and OH, supporting the hypothesis that OH might be a marker for disease progression and cognitive decline in PD.

Allan LM, Ballard CG, Burn DJ, Kenny RA. · Institute for Aging and Health, University of Newcastle upon Tyne, United Kingdom. · J Am Geriatr Soc. · Pubmed #16181166 No free full text.

Abstract: OBJECTIVES: To compare the prevalence, severity, and type of gait and balance disorders in Alzheimer's disease (AD), vascular dementia (VaD), Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB), Parkinson's disease without dementia (PD), and age-matched controls. DESIGN: Cross-sectional. SETTING: Secondary care clinics in geriatric psychiatry, neurology, and geriatrics. PARTICIPANTS: Two hundred forty-five participants aged 65 and older (AD, n=40; VaD, n=39; PDD, n=46; DLB, n=32; PD, n=46; and controls, n=42). MEASUREMENTS: Prevalence and severity of gait and balance disorders were assessed using the Tinetti gait and balance scale. The types of gait disorders in each diagnostic group were classified using the Nutt et al. classification. RESULTS: Gait and balance disorders were more common with PDD (93%), VaD (79%), and DLB (75%) than with PD (43%) and AD (25%) and in controls (7%). The risk of gait and balance disorder was higher in the non-Alzheimer's dementia groups (VaD, PDD, and DLB) than in the AD group (odds ratio=15 (95% confidence interval=6-37). If a gait disorder was present in mild dementia (Cambridge Examination for Mental Disorders of the Elderly cognitive subsection score >65), this was diagnostic of non-Alzheimer's dementia, with sensitivity of 78% and specificity of 100%. Non-Alzheimer's dementia groups had worse Tinetti gait and balance scores than the AD group (all P<.001). The types of gait disorders discriminated between non-Alzheimer's dementias. CONCLUSION: The findings support the idea that gait and balance assessment may augment the diagnostic evaluation of dementia.

Allcock LM, Ullyart K, Kenny RA, Burn DJ. · Parkinson's Disease Research Unit, Department of Neurology, Sunderland Royal Hospital and Institute for Ageing and Health, University of Newcastle, Sunderland, UK. · J Neurol Neurosurg Psychiatry. · Pubmed #15377699 links to  free full text

Abstract: The frequency of orthostatic hypotension (OH) in cohorts of patients recruited through hospital Parkinson's disease (PD) clinics ranges from 16% to 58%. However, hospital based cohorts may be subject to ascertainment bias. The aim of this study was to determine the frequency of OH in a community based population of PD patients and to determine the demographic features of patients with and without OH.Forty two (47%) of patients met the criteria for OH. Subjects with OH were older than those without OH, but there was no difference in PD disease duration or severity, MMSE or depression rating between the groups.