Biomedical subjects

J T O'Brien

Publications and source records attributed to J T O'Brien.

At least 19 recordsLinked to original sources

PubMed2006

Alpha4beta2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography.

BACKGROUND: Loss of the alpha4beta2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease. OBJECTIVE: To investigate in vivo changes in this receptor using single-photon-emission CT (SPECT) with 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the alpha4beta2 receptor. METHODS: 32 non-smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation. RESULTS: Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p = 0.004; right, p = 0.002), striatal (left, p = 0.004; right, p = 0.003), right medial temporal (p = 0.04) and pons (p<0.001) in patients with AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both patients with AD and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD. CONCLUSION: Using 123I-5IA-85380 SPECT we found changes consistent with significant reductions in the nicotinic alpha4beta2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring progression of the disease and response to treatment in patients with AD and related diseases.

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PubMed2006

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.

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PubMed2006

A periodically active pulsar giving insight into magnetospheric physics.

PSR B1931+24 (J1933+2421) behaves as an ordinary isolated radio pulsar during active phases that are 5 to 10 days long. However, when the radio emission ceases, it switches off in less than 10 seconds and remains undetectable for the next 25 to 35 days, then switches on again. This pattern repeats quasi-periodically. The origin of this behavior is unclear. Even more remarkably, the pulsar rotation slows down 50% faster when it is on than when it is off. This indicates a massive increase in magnetospheric currents when the pulsar switches on, proving that pulsar wind plays a substantial role in pulsar spin-down. This allows us, for the first time, to estimate the magnetospheric currents in a pulsar magnetosphere during the occurrence of radio emission.

Journal Article↗

PubMed2006

Transient radio bursts from rotating neutron stars.

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.

Journal Article↗

PubMed2006

A study of the serotonin transporter in the prefrontal cortex in late-life depression and Alzheimer's disease with and without depression.

Previous studies investigating the serotonin transporter (SERT) in depression have been inconsistent and included a large proportion of subjects who had committed suicide. In Alzheimer's disease studies have generally reported a reduction in SERT density but have not compared Alzheimer's disease subjects with and without comorbid major depression. We conducted a post mortem study of SERT density in the prefrontal cortex in normal elderly, a group of elderly depressed subjects and in Alzheimer's disease subjects with and without major depression. A post mortem study comparing SERT density in the prefrontal cortex in elderly controls (n = 10), subjects with major depression (n = 8) and subjects with Alzheimer's disease with (n = 9) and without (n = 5) comorbid major depression. We used autoradiography to measure the density of [3H]CN-IMI binding (non-specific binding determined with citalopram) to the SERT in the prefrontal cortex. We found a marked reduction in specific SERT binding in the prefrontal cortex in Alzheimer's disease subjects compared with both control (P = 0.002) and depressed subjects (P = 0.004) but no difference in SERT binding between depressed and control subjects or between Alzheimer's disease subjects with and without depression. Our study confirms previous reports of a reduction in SERT binding in Alzheimer's disease but indicates this reduction is not greater in Alzheimer's disease subjects who also have had major depression. In a group of subjects more typical of late-life depression we did not identify any alterations in SERT density.

Age of Onset↗

PubMed2006

Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies.

BACKGROUND: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson's disease (PD). AIMS: (1) To examine rates of cognitive and motor decline over two years in PD (n=40), PDD (n=42) and DLB (n=41) subjects, compared with age matched controls (n=41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. RESULTS: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE -4.5 and -3.9, respectively), compared with PD (-0.2) and controls (-0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (chi2=6.7, Fisher's exact test p<0.05). CONCLUSION: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.

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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

Temporal lobe atrophy on MRI in Parkinson disease with dementia: a comparison with Alzheimer disease and dementia with Lewy bodies.

OBJECTIVE: To investigate the extent of medial temporal lobe atrophy (MTA) on MRI in Parkinson disease (PD) with and without dementia compared with Alzheimer disease (AD) and dementia with Lewy bodies (DLB) and to determine whether MTA correlates with cognitive impairment in PD and PD dementia (PDD). METHODS: Coronal T1-weighted MRI scans were acquired from control subjects (n = 39) and patients with PD (n = 33), PDD (n = 31), DLB (n = 25), and AD (n = 31), diagnosed according to standardized clinical diagnostic criteria. Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized (Scheltens) scale. RESULTS: More severe MTA was seen in PDD (p = 0.007), DLB (p < 0.001), and AD (p < 0.001) vs control subjects. PD subjects had greater hippocampal atrophy than control subjects (p = 0.015) but less than subjects with DLB and AD, though not with PDD. MTA correlated with CAMCOG score and memory scores in the DLB group and with age in control, PDD, and AD groups. There were no correlations between MTA and cognitive impairment in PD, PDD, and AD. PDD and DLB had a similar profile of cognitive impairment and MTA. CONCLUSIONS: Medial temporal lobe atrophy (MTA) was seen in cognitively intact older subjects with Parkinson disease (PD) and was not more pronounced in Parkinson disease dementia (PDD). Alzheimer disease (AD) and, to a lesser extent, dementia with Lewy bodies (DLB) showed more pronounced MTA. Results suggest early hippocampal involvement in PD and that when dementia develops in PD, anatomic structures apart from the hippocampus are predominantly implicated. Greater hippocampal involvement in AD vs PDD and DLB is consistent with clinical, cognitive, and pathologic differences between the disorders.

Age Factors↗

PubMed2005

Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

BACKGROUND: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in cortisol level. METHODS: We studied 187 patients aged over 60 years undergoing major non-cardiac surgery with general or regional anaesthesia. Saliva cortisol levels were measured pre-operatively and at 1 day, 7 days and 3 months post-operatively in the morning (08.00 h) and in the afternoon (16.00 h) using salivettes. Cognitive function was assessed pre-operatively, on day 7 and at 3 months using four neuropsychological tests. POCD was defined as a combined Z score of greater than 1.96. RESULTS: After surgery, salivary cortisol concentrations increased significantly. POCD was detected in 18.8% of subjects at 1 week and in 15.2% after 3 months. The pre-operative ratios between the morning and afternoon cortisol concentrations (am/pm ratios) were 2.8 and 2.7 in patients with POCD at 1 week vs. those without POCD at 1 week, respectively. The am/pm ratios decreased significantly post-operatively to 1.9 and 1.6 at 1 week, respectively (P = 0.02 for both). In an analysis considering all am/pm ratios, it was found that the persistent flattening in am/pm ratio was significantly related to POCD at 1 week. CONCLUSION: The pattern of diurnal variation in cortisol level was significantly related to POCD. Thus, circadian rhythm disturbance or metabolic endocrine stress could be an important mechanism in the development of cognitive dysfunction after major surgery.

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PubMed2005

The role of levodopa in the management of dementia with Lewy bodies.

BACKGROUND: One of the core clinical features of dementia with Lewy bodies (DLB) is extrapyramidal syndrome (EPS). Levodopa is currently the gold standard oral therapy for Parkinson's disease (PD), but its use in DLB has been tempered by concerns of exacerbating neuropsychiatric symptoms. AIM: To assess the efficacy and tolerability of L-dopa in managing EPS in DLB and to compare the motor response with that seen in PD and PD with dementia (PDD). METHOD: EPS assessment consisted of the Unified Parkinson's Disease Rating Scale, motor subsection (UPDRS III), and finger tapping and walking tests. Patients with DLB were commenced on L-dopa. After 6 months, patients were examined in the "off" state, given L-dopa and assessed for motor responses. Identical assessments were performed in patients with PD and PDD also receiving L-dopa. RESULTS: Acute L-dopa challenge in 14 DLB patients yielded a mean 13.8% (p = 0.02) improvement in UPDRS III score, compared with 20.5% in PD (n = 28, p < 0.0001) and 23% in PDD (n = 30, p<0.0001) respectively. Finger tapping scores increased (12.3% v 20% and 23%), while walking test scores decreased (32% v 41% and 67%). Of the DLB patients, 36% were classified as "responders" on L-dopa challenge, compared with 70% of the PDD and 57% of the PD patients. Nineteen DLB patients were treated for 6 months with L-dopa (mean daily dose 323 mg). Two withdrew prematurely with gastrointestinal symptoms and two with worsening confusion. CONCLUSION: L-dopa was generally well tolerated in DLB but produced a significant motor response in only about one third of patients. Younger DLB cases were more likely to respond to dopaminergic treatment.

Administration, Oral↗

PubMed2005

Longitudinal change in 99mTcHMPAO cerebral perfusion SPECT in Parkinson's disease over one year.

BACKGROUND: Brain perfusion deficits have been reported previously in subjects with Parkinson's disease in comparison with healthy controls. OBJECTIVE: To carry out a longitudinal study of perfusion in patients with Parkinson's disease and controls to find areas showing a reduction in perfusion over one year. METHODS: Two HMPAO cerebral perfusion scans were acquired one year apart in 30 subjects with Parkinson's disease (mean (SD) age, 76 (5) years) and 34 healthy comparison subjects (76 (7) years). Scans were normalised to the mean intensity in the cerebellum. RESULTS: Using SPM99 within groups to investigate regions that showed a decrease in perfusion between scans, it was found that in Parkinson's disease subjects but not controls there was a significant cluster in the frontal lobe (Brodmann area 10) where perfusion decreased over the year. CONCLUSIONS: The progressive frontal perfusion deficits in Parkinson's disease are consistent with results from previous structural and neuropsychological studies suggesting frontal lobe involvement and executive dysfunction even in early Parkinson's disease.

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PubMed2004

Visual perception in Parkinson disease dementia and dementia with Lewy bodies.

OBJECTIVE: To quantify visual discrimination, space-motion, and object-form perception in patients with Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). METHODS: The authors used a cross-sectional study to compare three demented groups matched for overall dementia severity (PDD: n = 24; DLB: n = 20; AD: n = 23) and two age-, sex-, and education-matched control groups (PD: n = 24, normal controls [NC]: n = 25). RESULTS: Visual perception was globally more impaired in PDD than in nondemented controls (NC, PD), but was not different from DLB. Compared to AD, PDD patients tended to perform worse in all perceptual scores. Visual perception of patients with PDD/DLB and visual hallucinations was significantly worse than in patients without hallucinations. CONCLUSIONS: Parkinson disease dementia (PDD) is associated with profound visuoperceptual impairments similar to dementia with Lewy bodies (DLB) but different from Alzheimer disease. These findings are consistent with previous neuroimaging studies reporting hypoactivity in cortical areas involved in visual processing in PDD and DLB.

Activities of Daily Living↗

PubMed2004

Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects.

OBJECTIVE: To determine the potential role of whole brain atrophy, hippocampal atrophy, or both, and small vessel disease/white matter lesions as mechanisms underlying the cognitive impairment associated with hypertension. METHODS: Using MRI scanning the authors determined hippocampal volumes, whole brain volumes, and location and severity of white matter lesions, using Scheltens scale, in 103 hypertensive (166 +/- 8/88 +/- 7 mm Hg, 54 female) and 51 normotensive (132 +/- 12/74 +/- 7 mm Hg, 21 female) subjects age > or = 70 years. RESULTS: Compared to normotensive subjects, older hypertensive subjects had significantly smaller whole brain volumes (887 +/- 109 vs 930 +/- 97 cm3, p = 0.02) and nonsignificantly reduced hippocampal volumes (5.39 +/- 1.60 vs 5.67 +/- 1.80 cm3, p = 0.33). Hypertensive subjects had an increased burden of periventricular lesions: bands (p = 0.03), frontal caps (p = 0.08), occipital caps (p = 0.07), and total periventricular hyperintensities (p = 0.02). They also had higher scores in subcortical areas: frontal (p = 0.04), temporal (p = 0.03), and deep white matter areas (p = 0.05). A correlation was found between whole brain volumes and systolic blood pressure (r = -0.19, p = 0.02). No correlation was seen between whole brain volumes and white matter lesion burden. CONCLUSIONS: Moderate hypertension in non-impaired older subjects is associated with smaller whole brain volume and an increased burden of subcortical and periventricular white matter lesions.

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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

The application of serial MRI analysis techniques to the study of cerebral atrophy in late-onset dementia.

We have used a serial MR image analysis technique previously developed for studies of cerebral atrophy in early-onset dementia and applied it to a study of late-onset dementia patients with images acquired using a different scanner and scan sequence. Validation and optimisation tests showed that with only small changes to key analysis parameters the technique can successfully be applied to previously untested data with dissimilar image characteristics. The overall accuracy in estimation of cerebral atrophy using the technique was determined to be between 2 and 4 ml (1sigma) depending on the conditions during image acquisition. By comparing the results of alternative registration techniques we demonstrate the potential of using of fully automated 9 DOF image registration as an effective and efficient means of correcting for scanner pixel size variations, even in the presence of significant cerebral atrophy. Applied to the late-onset dementia study, patients were found to have significantly increased mean atrophy rates (p<0.001) compared to controls. In general the analysis technique is shown to be a robust, accurate and transferable tool of potential value for future studies of dementia and related neuro-degenerative disorders.

Adult↗

PubMed2004

Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain.

White matter lesions (WML) on magnetic resonance imaging (MRI) brain scans are associated with ageing. They are unrelated to specific disorders, and their impact on cognitive and other brain functions is poorly characterized. Pathological studies often omit systematic survey of WML because of the need to study multiple full coronal tissue blocks, and uncertainty over the significance of lesions identified in periventricular and deep subcortical regions. Post-mortem MRI provides a means of mapping WML but the sensitivity and specificity of the method are unresolved. In this study post-mortem MRI of WML in fixed brain slices was compared with pathology in 33 brains donated to the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). This study shows that MRI detection of WML was less sensitive than pathology: periventricaular lesions (PVL) sensitivity = 95% (87-99%), specificity = 71% (44-90%); deep subcortical lesions (DSCL) sensitivity = 86% (79-93%), specificity = 80% (72-88%). False negative MRI was associated with milder pathology, but lesions detected by myelin attenuation alone showed both microglial and endothelial activation. Therefore post-mortem MRI of formalin-fixed brain slices is a reliable method to obtain systematic data on the severity and distribution of cerebral white matter disease, and appears to detect those WML most likely to have clinical impact.

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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