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Biomedical subjects

R A Kenny

Publications and source records attributed to R A Kenny.

At least 19 recordsLinked to original sources
PubMed2006

Autonomic dysfunction in dementia.

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.

Aged↗
PubMed2006

Cerebral autoregulation is impaired in cardioinhibitory carotid sinus syndrome.

OBJECTIVES: To compare changes in cerebral autoregulation in response to controlled, lower body negative pressure-induced hypotension in patients with carotid sinus syndrome (CSS) and case controls. DESIGN: Prospective case controlled study. SETTING: Secondary and tertiary referral falls and syncope service. PATIENTS: 17 consecutive patients with CSS and 11 asymptomatic controls. INTERVENTIONS: Hypotension insufficient to cause syncope induced by lower body negative pressure (minimum 30 mm Hg fall in systolic blood pressure (SBP)) during concomitant transcranial Doppler ultrasonography. MAIN OUTCOME MEASURES: Cerebral autoregulation (systolic, diastolic and mean middle cerebral arterial blood flow velocities and cerebrovascular resistance) with continuous end-tidal carbon dioxide and haemodynamic monitoring. RESULTS: Cerebral autoregulatory indices differed significantly between patients with CSS and controls. Systolic, diastolic and middle cerebral arterial blood flow velocities were, respectively, 9.2 m/s (95% confidence interval (CI) 2.9 to 15.4 m/s), 4.7 m/s (95% CI 1.5 to 7.9 m/s) and 6.9 m/s (95% CI 2.5 to 11.4 m/s) slower in patients with CSS. Cerebrovascular resistance was significantly greater in patients with CSS than in controls at SBP nadir and suction release; differences were 0.9 mm Hg/m/s (95% CI 0.0 to 1.7 mm Hg/m/s) and 0.8 mm Hg/m/s (95% CI 0.0 to 1.7 mm Hg/m/s), respectively. End-tidal carbon dioxide and systemic haemodynamic variables were similar for patients and controls at baseline and during lower body negative pressure. CONCLUSIONS: Cerebral autoregulation is altered in patients with CSS. This difference may have aetiological implications in the differential presentation with falls and drop attacks rather than syncope.

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PubMed2006

Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia.

Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta peptides extracted from temporal and frontal cortices were quantified using a previously characterized sensitive homogenous time-resolved fluorescence (HTRF) assay. The HTRF assays and immunocapture mass spectrometric analyses revealed that the Abeta(42) species were by far the predominant form of extractable peptide compared with Abeta(40) peptide in VaD brains. The strong signal intensity for the peak representing Abeta(4-42) peptide confirmed that these N-terminally truncated species are relatively abundant. Absolute quantification by HTRF assay showed that the mean amount of total Abeta(42) recovered from VaD samples was approximately 50% of that in AD, and twice that in the age-matched controls. Linear correlation analysis further revealed an increased accumulation with age of both Abeta peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable Abeta(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain Abeta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age.

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PubMed2006

Carotid sinus hypersensitivity associated with focal alpha-synucleinopathy of the autonomic nervous system.

A case of an 82-year-old woman who experienced repeated falls is described. She exhibited a cardioinhibitory carotid sinus hypersensitivity after right carotid sinus massage (CSM), but without evidence of orthostatic hypotension. After a pacemaker was implanted, she did not experience any falls, dizziness or syncope. Her balance eventually deteriorated, but she remained cognitively intact and died from lung cancer at the age of 89 years. Neuropathological examination showed only age-related Alzheimer's disease pathology and a few alpha-synuclein-positive granular deposits and neurites in the dorsal nucleus of the vagus and solitary tract nucleus in the medulla, but a marked alpha-synuclein pathology in the stellate ganglia. The cardioinhibitory element of her CSM was possibly because of the alpha-synuclein pathology in the ganglion, which impaired sympathetic transmission. This case shows another phenotype among patients with alpha-synucleinopathy.

Accidental Falls↗
PubMed2005

Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.

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.

Brain↗
PubMed2005

Impact of hypertension and apolipoprotein E4 on poststroke cognition in subjects >75 years of age.

BACKGROUND AND PURPOSE: The apolipoprotein E4 allele (APOE4) associates with increased dementia risk, and hypertension may associate with mild cognitive deficits. We examined whether nondemented stroke patients with (1) a prestroke history of hypertension and (2) APOE4 were more cognitively impaired at 3 months after stroke. METHODS: A total of 257 participants were genotyped and outcomes from neuropsychological evaluations analyzed using regression. RESULTS: Total Cambridge Assessment for Mental Disorders in the Elderly (CAMCOG) and speed of working memory significantly associated with hypertension. No outcomes significantly associated with APOE4. CONCLUSIONS: Subjects with prestroke hypertension had more impaired global cognition and slower access to information held in working memory.

Age Factors↗
PubMed2004

Autonomic function assessed by heart rate variability is normal in Alzheimer's disease and vascular dementia.

Heart rate variability (HRV) is a sensitive method for the assessment of autonomic function and requires little cooperation from the subject, making it suitable for use in dementia. Preliminary studies have suggested that HRV may be impaired in Alzheimer's disease (AD). HRV has not been studied in vascular dementia (VAD). We investigate autonomic function in AD and VAD, using power spectral analysis of HRV. One hundred and fourteen participants were evaluated (14 AD, 20 VAD and 80 controls). The resting ECG was recorded for 5 min with participants in the supine position. Power spectral analysis used to obtain spectral bands in the very-low-frequency (<0.04 Hz), low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) bands and total spectral power (<0.40 Hz) according to international HRV guidelines. There were no differences in HRV in patients with AD or VAD when compared with controls.

Aged↗
PubMed2004

APOE epsilon4 and cognitive decline in older stroke patients with early cognitive impairment.

BACKGROUND: Dementia is common post stroke, but the potential role of early cognitive impairment and APOE epsilon4 as risk factors is unclear. METHOD: Stroke survivors older than 75 years without dementia at 3 months post stroke received a detailed neuropsychological evaluation at 3 and 15 months post stroke, which included the Cambridge Assessment of Mental Disorders in the Elderly (CAMCOG). Early cognitive impairment was diagnosed using the criteria for cognitive impairment/no dementia (vascular CIND). APOE genotype was determined using a standardized method. RESULTS: One hundred thirty-seven older stroke patients without dementia (mean age 80.6 +/- 4.3, mean CAMCOG score 83.5 +/- 10.4, 68 women) participated in the study, of whom 40 met the criteria for CIND. Stroke patients with one or more APOE epsilon4 alleles were significantly more likely to have CIND (14/40 vs 17/97, odds ratio = 2.5, 95% CI 1.1 to 5.8). Over the 1 year of follow-up, CIND patients with one or more APOE epsilon4 alleles had a mean decline on the total CAMCOG of 2.7 points compared with an improvement of >4 points among patients without APOE epsilon4 (T = 2.9 p = 0.006). CIND patients with an APOE epsilon4 allele also experienced greater decline in memory (T = 2.5, p = 0.015). CONCLUSION: In older stroke patients with early cognitive impairment, the presence of an APOE epsilon4 allele is associated with greater progression of cognitive decline. This has implications for interventions aimed at the secondary prevention of dementia in stroke patients.

Age Factors↗
PubMed2004

NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia.

OBJECTIVE: To determine the utility of the neuroimaging component within the National Institute of Neurological Disorders and Stroke (NINDS) Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for vascular dementia for distinguishing between patients with and without dementia in the context of cerebrovascular disease. METHOD: One hundred twenty-five poststroke patients age > or =75 (27 with and 98 without poststroke dementia) from representative hospital-based stroke registers in the North East of England were evaluated using a 1.5 T MR scanner. The proportion of patients with and without poststroke dementia meeting the imaging component of the NINDS AIREN criteria was determined, and hippocampal atrophy (measured using the Schelten scale) was compared between the two groups. RESULTS: There were no significant differences between the patients with and without poststroke dementia on any criteria of the imaging parameters within the NINDS AIREN criteria. In addition, there were no significant differences in the number or size of cortical or subcortical infarcts between the two groups, with 13 patients without dementia having cortical infarcts >50 mm. Patients with dementia had greater hippocampal atrophy (right: Mann-Whitney U test, Z = 2.5, p = 0.01; left: Mann-Whitney U test, Z = 2.5, p = 0.01). CONCLUSION: The neuroimaging component of the NINDS AIREN criteria does not distinguish between older patients with and without poststroke dementia.

Aged↗
PubMed2004

Neuropsychological characteristics of mild vascular cognitive impairment and dementia after stroke.

BACKGROUND: Post-stroke cognitive impairment is frequent, with characteristic impairments of attentional and executive performance. OBJECTIVE: The study aims to determine whether the profile and severity of impairment in vascular Cognitive Impairment No Dementia (vascular CIND) is intermediate between that seen in stroke patients without significant cognitive impairment and patients with post-stroke dementia and thus to establish if the potential value of vascular CIND is a useful concept for predicting further cognitive decline and dementia in stroke patients. METHODS: Stroke patients (n=381) > 75 were recruited from representative hospital-based stroke registers in Tyneside and Wearside, UK. Sixty six age matched controls were also recruited. A detailed battery of neuropsychological assessments was completed 3 months post stroke. RESULTS: Deficits of attention (z=5.7; p <0.0001) and executive function (z=5.9; p <0.0001) were seen even in stroke patients without vascular CIND, compared to controls. However, stroke patients with CIND were significantly more impaired again on tests of executive function (z=10.3; p <0.0001) compared to those not meeting CIND criteria; and also had greater impairments of memory (z=10.4; p <0.0001) and language expression (z=10.1; p <0.0001). A similar overall profile of deficits was evident in the CIND and the dementia group, but specific deficits were significantly more pronounced in those with dementia, particularly in orientation (z=7.2; p <0.0001) and memory (z=5.8; p <0.0001). CONCLUSIONS: The current study indicates that attentional and executive impairments are frequent in stroke patients, but deficits of memory, orientation and language are more indicative of CIND and dementia. Further longitudinal studies are required to clarify the relationship between specific lesions and the progression of specific cognitive deficits in post-stroke patients.

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PubMed2004

Individualised quality of life after pacing. Does mode matter?

AIMS: To examine the hypothesis that atrial based pacing improves Quality of Life (QoL) after pacing by undertaking a detailed QoL evaluation that includes an individualised assessment as well as disease specific evaluation. METHODS: Prospective study of patients randomised to VVI(R) or atrial based pacing modes using the Schedule for the Evaluation of Individual QoL (SEIQoL), the 36-item Medical Outcomes Study Short-Form General Health Survey (SF36), and a modified version of the Karolinska Cardiovascular Symptomatology Questionnaire (KCSQ). RESULTS: Seventy-three patients completed the two-year follow up of the study. Pacing improved SEIQoL scores, cardiovascular symptoms and the physical role limitation, social limitation and mental health domains of SF36 from baseline to one month. Pacing mode had no effect on QoL the major determinants of which were baseline QoL and a history of coronary artery disease. CONCLUSION: Atrial based pacing does not improve QoL in the two years after pacing when compared with VVI(R) pacing.

Aged↗
PubMed2004

Carotid sinus syndrome is common in dementia with Lewy bodies and correlates with deep white matter lesions.

BACKGROUND: Carotid sinus syndrome (CSS) is a common cause of syncope in older persons. There appears to be a high prevalence of carotid sinus hypersensitivity (CSH) in patients with dementia with Lewy bodies (DLB) but not in Alzheimer's disease. OBJECTIVE: To compare the prevalence of CSH in DLB and Alzheimer's disease, and to determine whether there is an association between CSH induced hypotension and brain white matter hyperintensities on magnetic resonance imaging (MRI). METHODS: Prevalence of CSH was compared in 38 patients with DLB (mean (SD) age, 76 (7) years), 52 with Alzheimer's disease (80 (6) years), and 31 case controls (73 (5) years) during right sided supine carotid sinus massage (CSM). CSH was defined as cardioinhibitory (CICSH; >3 s asystole) or vasodepressor (VDCSH; >30 mm Hg fall in systolic blood pressure (SBP)). T2 weighted brain MRI was done in 45 patients (23 DLB, 22 Alzheimer). Hyperintensities were rated by the Scheltens scale. RESULTS: Overall heart rate response to CSM was slower (RR interval = 3370 ms (640 to 9400)) and the proportion of patients with CICSH greater (32%) in DLB than in Alzheimer's disease (1570 (720 to 7800); 11.1%) or controls (1600 (720 to 3300); 3.2%) (p<0.01)). The strongest predictor of heart rate slowing and CSH was a diagnosis of DLB (Wald 8.0, p<0.005). The fall in SBP during carotid sinus massage was greater with DLB (40 (22) mm Hg) than with Alzheimer's disease (30 (19) mm Hg) or controls (24 (19) mm Hg) (both p<0.02). Deep white matter hyperintensities were present in 29 patients (64%). In DLB, there was a correlation between magnitude of fall in SBP during CSM and severity of deep white matter changes (R = 0.58, p = 0.005). CONCLUSIONS: Heart rate responses to CSM are prolonged in patients with DLB, causing hypotension. Deep white matter changes from microvascular disease correlated with the fall in SBP. Microvascular pathology is a key substrate of cognitive impairment and could be reversible in DLB where there are exaggerated heart rate responses to carotid sinus stimulation.

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PubMed2004

Frequency of orthostatic hypotension in a community based cohort of patients with Parkinson's disease.

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.

Aged↗
PubMed2003

Cognitive behavioural therapy as a potential treatment for vasovagal/neurocardiogenic syncope--a pilot study.

Vasovagal syncope (VVS) is an exaggerated tendency to the common faint that affects any age group. Conventional treatment is non-specific and involves strategies to increase blood pressure. Patients with VVS are often unable to work or complete education due to actual, or fear of, syncopal symptoms. Here we present a series of nine patients with VVS whose symptoms had proved resistant to conventional treatments where intervention with cognitive behavioural therapy (CBT) led to significant reductions in reported syncopal episodes and consultations at our unit. All subjects post-intervention were able to return to work or schooling. CBT is an effective treatment in those with difficult to manage VVS. Randomized controlled trials are needed.

Adolescent↗
PubMed2003

Cardiovascular effects of donepezil in patients with dementia.

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer's disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms2; p = 0.001) but also for total power (median changed from 1,563 to 844 ms2; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

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