Characterising the Neuropsychological Profile of Psychotic Symptoms in Alzheimer’s Disease and Imaging D2/3 Receptor Occupancy During Treatment

Abstract

BackgroundPsychotic symptoms occur in approximately 40% of patients with Alzheimer’s disease (AD) and have been linked with striatal dopamine (D2/3) receptor function. The first component of the thesis aims to investigate the neuropsychological profile accompanying psychotic symptoms in AD, and establish whether cognitive and motor tasks which have a documented association with dopaminergic function might be markers of psychotic symptoms and delusional subtypes in AD. Dopamine D2/3 receptor occupancy studies have been instrumental in guiding antipsychotic prescribing in schizophrenia. The second part of the thesis aims to adapt [18F]fallypride imaging for use in healthy older people and in dopamine (D2/3) receptor occupancy studies in AD.
MethodsNeuropsychology: 70 AD subjects aged between 65 and 95 years were categorised into psychotic (n=34) and non-psychotic (n=36) groups, based on carer-rated scales, and then compared using a hypothesis-driven test battery.Imaging: Eight healthy older (>65 years) adults were scanned twice, 4-6 weeks apart. [18F]fallypride binding potential (BPND) was determined and test-retest variability and intraclass correlation coefficient (ICC) values were calculated. A further six subjects with AD were recruited prior to commencing amisulpride treatment. [18F]fallypride BPND pre/post 2-8 weeks of amisulpride treatment and D2/3 occupancy was measured.
ResultsNeuropsychology: Subjects with psychotic symptoms, in particular misidentification phenomena, had significantly poorer sustained attentional and visuoperceptual function.Imaging: The adapted [18F]fallypride scanning protocol showed high reproducibility and reliability in all but the prefrontal regions and was generally well tolerated in AD subjects.
ConclusionNeuropsychology: Sustained attention deficits may act as a marker of psychotic symptoms in AD due to associations with dopaminergic function in the associative striatum. Visuoperceptual deficits may indicate additional pathology in the ventral visual stream, which could characterize the misidentification subgroup.Imaging: The feasibility of an adapted scanning protocol was demonstrated in AD subjects and represents the first step towards defining a ‘therapeutic window’ of D2/3 occupancy to guide antipsychotic prescribing in AD.

Date of Award	2014
Original language	English
Awarding Institution	King's College London
Supervisor	Robert Howard (Supervisor) & Suzanne Reeves (Supervisor)