Biomedical subjects

Sanjeet Pakrasi

Publications and source records attributed to Sanjeet Pakrasi.

5 recordsLinked to original sources

PubMed2006

In vivo SPECT imaging of muscarinic acetylcholine receptors using (R,R) 123I-QNB in dementia with Lewy bodies and Parkinson's disease dementia.

INTRODUCTION: Alterations in cholinergic function have been reported to be associated with dementia. The aim of this study was to investigate differences in the distribution of muscarinic acetylcholine receptors (mAChRs) using (R,R) 123I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and age-matched controls. 123I-QNB binding was also compared to the corresponding cerebral perfusion changes in the same subjects. METHODS: 63 subjects (24 controls, 14 DLB, 25 PDD) underwent 123I-QNB and perfusion 99mTc-exametazine SPECT scanning. Image analysis, using statistical parametric mapping (SPM99), involved spatial normalisation of each image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean whole brain uptake. Group effects and correlations were assessed using two sample t tests and linear regression respectively. RESULTS: Relative to controls, significant elevation of 123I-QNB binding was apparent in the right occipital lobe in DLB and right and left occipital lobes in PDD (height threshold p<or=0.001 uncorrected). PDD also showed significant loss in uptake in frontal regions and temporal lobes bilaterally that was not present in DLB. These patterns appeared to be independent of any corresponding rCBF changes. CONCLUSION: Significant elevation of mAChRs in the occipital lobe was associated with DLB and PDD. This may relate to the visual disturbances that are prevalent in these disorders. Further studies are required in order to establish the role of mAChRs in visual function.

Aged↗

PubMed2006

Cholinesterase inhibitors in advanced Dementia with Lewy bodies: increase or stop?

INTRODUCTION: There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. METHOD: We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15 mg) to resolve rehyphen;emergent neuropsychiatric symptoms. RESULTS: The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. CONCLUSION: Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms.

Cholinesterase Inhibitors↗

PubMed2005

White matter hyperintensities and depression--preliminary results from the LADIS study.

BACKGROUND: White matter hyperintensities have been associated with the development of depression in older subjects, though the details of this relationship are not fully understood. METHODS: In a pan-European multicentre study of 629 older subjects, we examined the relationship between MRI white matter hyperintensities (WMH), depressive symptoms and self perceived health quality of life (QOL). WMH were rated using a three-point scale. RESULTS: We found depressive symptoms as assessed by the geriatric depression 15-item scale to be associated with WMH rating (Spearman's rho 0.11, p = 0.008) and also with the Euro-QOL health score (Spearman's rho -0.5, p < 0.001). In a ordinal logistic regression model, QOL was found to strongly predict GDS score (p < 0.001) and severe vs mild WMH were associated with increased depression (p = 0.028). The relationship between history of severe depression and WMH score was examined, but there were no differences either between those with and without a history of severe depression, or those with an early vs late onset of depression. CONCLUSIONS: The results suggest that WMH play a role in increasing depressive symptoms, even when perceived quality of life is controlled for as a possible mediating factor.

Aged↗

PubMed2005

A comparison of the efficacy of donepezil in Parkinson's disease with dementia and dementia with Lewy bodies.

BACKGROUND: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) overlap in phenomenology and neurochemical deficits. We hypothesised they would not differ in their response to the cholinesterase inhibitor donepezil. METHODS: We recruited 70 subjects, 30 DLB and 40 PDD, in an open label study to compare the efficacy of donepezil in these two patient groups. They were assessed at baseline, 4, 12 and 20 weeks. The main outcome measures were the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and motor sub-section of the Unified Parkinson's Disease Rating Scale (UPDRS III). RESULTS: PDD patients were younger than DLB and had more severe parkinsonism at baseline. The groups were similar on all other variables of interest. By 20 weeks the mean MMSE score increased by 3.9 points in the DLB group and by 3.2 points in PDD. The mean NPI score reduced by 14.6 points for DLB and 12.0 points for PDD. These treatment effects were all significant compared to baseline (p < 0.001) but there were no significant between-group treatment differences (MMSE p = 0.56, NPI p = 0.39). UPDRS III motor scores did not change significantly from baseline values in either group. Although adverse effects were common (69%) they were usually mild and 64 patients (91%) completed the study. The four patients who did withdraw with adverse effects all had a PDD diagnosis. CONCLUSIONS: Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.

Age Factors↗

PubMed2005

Emission tomography in dementia.

Dementia is a chronic brain syndrome with enormous impact on health care provision. Emission tomography (single photon emission computed tomography (SPECT) and positron emission tomography (PET)) provides a unique tool to investigate functional and neurochemical changes, both in those with established dementia and in those at risk of subsequent cognitive decline. Alzheimer's disease is characterized by bilateral temporoparietal hypoperfusion on SPECT and hypometabolism on PET, which may precede the onset of dementia as similar changes can be demonstrated in those with mild cognitive impairment and in those genetically at risk of developing Alzheimer's disease. In dementia with Lewy bodies medial parietal and occipital perfusion deficits are seen together with pre-synaptic and post-synaptic dopaminergic changes, most particularly a reduction in the striatal pre-synaptic dopamine transporter which can be visualized using appropriate ligands (e.g., (123)I-FP-CIT). Vascular dementia is associated with multiple, asymmetric, perfusion deficits in multi-infarct dementia. In contrast, subcortical vascular dementia is associated with reduced perfusion but preserved oxygen extraction fraction on PET. Fronto-temporal dementia is characterized by both hypometabolism and hypoperfusion in fronto-temporal lobes, though hypometabolism appears more extensive, affecting large areas of the cerebral hemispheres. Longitudinal studies of treatment response in Alzheimer's disease with cholinergic drugs have found changes in regional blood flow and nicotinic and muscarinic receptor function in those patients who respond to treatment. Currently, emission tomography is widely used for assisting with clinical differential diagnosis. Future developments will entail the development and application of more specific neurochemical ligands and those which bear a closer relationship to the underlying disease processes, including markers of tau, amyloid and synuclein pathology.

Brain↗