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The effects of donepezil on nicotinic receptor status in dementia: a 123I-5IA-85380 SPECT study
  1. S J Colloby1,
  2. S Pakrasi1,
  3. E K Perry1,
  4. S L Pimlott2,
  5. D J Wyper3,
  6. E D Williams4,
  7. I G McKeith1,
  8. J T O’Brien1
  1. 1
    Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, UK
  2. 2
    West of Scotland Radionuclide Dispensary, North Glasgow University Hospitals NHS Trust, Western Infirmary, Glasgow, UK
  3. 3
    Department of Clinical Physics, South Glasgow University Hospitals NHS Trust, Southern General Hospital, Glasgow, UK
  4. 4
    Regional Medical Physics Department, Sunderland Royal Hospital, Kayll Road, Sunderland, UK
  1. Dr Sean J Colloby, Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK; s.j.colloby{at}ncl.ac.uk

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Disturbances in the cerebral cholinergic nervous system and subsequent reduction of acetylcholine (ACh) are neurochemical features of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), and treatments with acetylcholinesterase inhibitors (AChEIs) offer symptomatic improvement in cognitive and non-cognitive symptoms. One important subclass of ACh receptors are nicotinic acetylcholine receptors (nAChRs), which have been shown to be implicated in memory and cognitive processes.

The SPECT tracer 123I-5IA-85380 is a radioligand that can visualise in vivo the presynaptic nAChR (α4β2 subtype, the most common subtype in man).1 In the present study, we assessed the effects of the AChEI donepezil on nicotinic receptor status in AD and DLB using 123I-5IA-85380 SPECT imaging. We hypothesised that relative 123I-5IA-85380 uptake would increase after administration of donepezil in accordance with previous studies using non-selective nicotinic ligands.2

Methods

Subjects

We recruited 9 non-smoking patients (for >10 years) with dementia (4 AD and 5 DLB). Patients with AD fulfilled NINCDS/ADRDA criteria for “probable” AD,3 whereas DLB subjects satisfied criteria for “probable” DLB.4 The study received ethical and ARSAC approval. All participants and their nearest relative gave informed written consent.

Assessments and study design

Prior to baseline 123I-5IA-85380 imaging, patients underwent physical, neurological and neuropsychiatric assessments. Tests included the Cambridge Cognitive Examination (CAMCOG), the Mini-Mental State Examination (MMSE) and the motor Unified Parkinson’s Disease Rating Scale (UPDRS III). Following …

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