Alzheimer Disease: Patterson J

Brown D, Chisholm JA, Owens J, Pimlott S, Patterson J, Wyper D. · Department of Psychiatry, Stobhill Hospital, Glasgow, UK. · Eur J Nucl Med Mol Imaging. · Pubmed #12552349 No free full text.

Abstract: An acetylcholine deficit remains the most consistent neurotransmitter abnormality found in Alzheimer's disease and various therapeutic agents have been targeted at this. In this study we investigated the action of Donepezil, a cholinesterase inhibitor that has few side-effects. In particular we set out to investigate whether muscarinic acetylcholine receptor (mAChR) availability influences the response to this therapy. We used the novel single-photon emission tomography (SPET) tracer (R, R)[(123)I]I-quinuclidinyl benzilate (R, R[(123)I]I-QNB), which has high affinity for the M1 subtype of mAChR. Regional cerebral perfusion was also assessed using technetium-99m hexamethylpropylene amine oxime. We investigated 20 patients on Donepezil treatment and ten age-matched controls. The results showed a reduction in (R, R)[(123)I]I-QNB binding in the caudal anterior cingulate in patients compared with controls and relatively high binding in the putamen and rostral anterior cingulate, suggesting a relative sparing of mAChR in these regions. The main finding of the study was that mAChR availability as assessed by (R, R)[(123)I]I-QNB binding did not distinguish responders from non-responders. Interestingly, we found that the extent of cognitive improvement showed no positive correlation with (R, R)[(123)I]I-QNB binding in any brain region but was inversely related to binding in the insular cortex. This suggests that, within the advised cognitive performance band for use of Donepezil, response is greater in those patients with evidence of a more marked cholinergic deficit. A larger study should investigate this.

Terrière E, Sharman M, Donaghey C, Herrmann L, Lonie J, Strachan M, Dougall N, Best J, Ebmeier KP, Pimlott S, Patterson J, Wyper D. · Division of Psychiatry, University of Edinburgh, Edinburgh, UK. · Neurochem Res. · Pubmed #17960479 No free full text.

Abstract: Five patients with Alzheimer's disease and five healthy volunteers were examined by SPECT with the nicotinic receptor ligand 123I-5-IA-85380. Patients were scanned before and after 6 weeks of treatment with donepezil. Quantification by regions of interest was reliable and the optimal normalisation procedure used cerebellar ratios. We found relative reductions in 5-IA binding capacity in patients in thalamus, frontal and central regions of interest of approximately one standard deviation unit (Cohen's d = 1). Reductions in binding after treatment with the acetylcholinesterase inhibitor donepezil of the same magnitude occurred in the brain stem. The study was clearly too small to confirm group differences, but it suggests that 5-IA can be used to examine both group differences and treatment effects in patients with Alzheimer's disease.

Taylor JP, Colloby SJ, McKeith IG, Burn DJ, Williams D, Patterson J, O'Brien JT. · Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. · J Neurol Neurosurg Psychiatry. · Pubmed #17299017 No free full text.

Abstract: BACKGROUND: 123I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) imaging is a diagnostic tool to help differentiate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, in animals, cholinesterase inhibitors (ChEi) have been reported to reduce radioligand binding to the striatal dopamine transporter. As ChEi are frequently used in people with dementia, it is important to determine whether their use affects 123I-FP-CIT uptake in the striatum. OBJECTIVE: To clarify whether chronic ChEi therapy modulates striatal dopamine transporter binding measured by 123I-FP-CIT in patients with AD, DLB and Parkinson's disease with dementia (PDD). DESIGN: Cross sectional study in 99 patients with AD (nine on ChEi, 25 not on ChEi), DLB (nine on ChEi, 19 not on ChEi) and PDD (six on ChEi, 31 not on ChEi) comparing 123I-FP-CIT striatal binding (caudate, anterior and posterior putamen) in patients receiving compared with those not receiving ChEi, correcting for key clinical variables including diagnosis, age, sex, Mini-Mental State Examination score, severity of parkinsonism and concurrent antidepressant use. RESULTS: As previously described, 123I-FP-CIT striatal uptake was lower in DLB and PDD subjects compared with those with AD. Median duration of ChEi use was 180 days. 123I-FP-CIT uptake was not significantly reduced in subjects receiving ChEi compared those not receiving ChEi (mean percentage reduction: AD 4.3%; DLB 0.7%; PDD 6.1%; p = 0.40). ChEi use did not differentially affect striatal 123FP-CIT uptake between patient groups (p = 0.83). CONCLUSIONS: Use of ChEi does not significantly influence the ability of 123I-FP-CIT imaging to distinguish AD from DLB.