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Expert Interview Alzheimer’s Disease
Psychotic Episodes in Alzheimer’s Disease
An expert interview with Clive Ballard
University of Exeter, Exeter, UK
Clive Ballard received his medical degree at the University of Leicester (UK). He subsequently specialised in psychiatry of older adults
and joined the Lewy Body Dementia Research Group. He was later appointed Professor of Age Related Disease and Director of the
Biomedical Research Unit for Dementia at King’s College London and is now the Executive Dean and Pro-Vice-Chancellor of the
University of Exeter Medical School (UK). His key research interests include neuropsychiatric symptoms in dementia, clinical trials of drug
and non-drug dementia therapies, genome wide association studies, non-Alzheimer dementias, and online intervention studies. He also
leads drug discovery initiatives and clinical trials associated with Alzheimer’s disease and non-Alzheimer’s dementias.
Keywords Psychosis, Alzheimer’s disease
Disclosure: In relation to this article, Clive Ballard
has declared that he received grant funding and
honoraria for advice from Acadia, the pharmaceutical
company who manufacture pimavanserin. This is an
expert interview and as such, has not undergone
the journal’s standard peer review process.
Acknowledgements: Editorial assistance was
provided by James Gilbart, Freelance Writer, and
was supported by Touch Medical Media.
Authorship: All named authors meet the International
Committee of Medical Journal Editors (ICMJE) criteria
for authorship of this manuscript, take responsibility
for the integrity of the work as a whole, and have
given final approval to the version to be published.
Open Access: This article is published under the
Creative Commons Attribution Noncommercial License,
which permits any non-commercial use, distribution,
adaptation and reproduction provided the original
author(s) and source are given appropriate credit.
Received: 6 October 2017
Published Online: 4 December 2017
Citation: European Neurological Review, 2017;12(2):60–1
Corresponding Author: Clive Ballard, University of
Exeter Medical School and Royal Devon and Exeter NHS
Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK.
Support: No funding was received in the publication
of this article.
sychotic episodes, particularly delusions, hallucinations, agitation, apathy, depression and
sleep disturbance are characteristic and harmful effects of Alzheimer’s disease (AD); they
are often the first manifestion of the condition and frequently appear before dementia
begins. Despite their importance, they are frequently unrecognised and are difficult to treat. There
is currently much interest in the mechanisms causing these symptoms, their impact on the disease
process and the possibility of new, more effective treatment approaches. In an expert interview,
Clive Ballard of Exeter University discusses the current situation of psychosis in AD.
Q: What are the prevalence and types of psychotic episodes in
Alzheimer’s disease (AD)?
Over 46 million people worldwide are estimated to live with dementia, of which approximately 75%
are attributable to AD. 1 The prevalence of AD increases rapidly after 65 years of age. At any one
time approximately 20–25% of people with AD experience psychotic symptoms, which become
more common at later stages. Over the entire course of the disease, 50–60% of patients with
AD experience at least one of these episodes. 2 In a study of 124 patients with dementia due to AD,
67% had psychotic symptoms occurring 2–6 times per week. For 32% of these patients, the
symptoms lasted for 12 weeks and recurred in 50% within 12 months. The frequencies of psychotic
episodes are greater in patients with Lewy bodies in brain neural cells. Hallucinations in AD tend to
be visual rather than auditory, tactile or olfactory, which distinguishes AD and Parkinson’s disease
(PD), schizophrenia, psychotic depression or mania. Persecutory delusions occur earlier in AD than
misidentification delusions; both types increase with dementia severity.
Q: How does the incidence of psychotic episodes affect disease
progression in AD?
Substantial evidence indicates that the presence of psychotic symptoms has a detrimental effect
on the course of AD. 2 Psychotic symptoms are associated with more aggressive disease and a
more rapid rate of decline. For example, this was demonstrated in two large cohort studies (n=335
and n=1,821) of patients with incident AD in which presence of clinically significant psychotic
symptoms was strongly associated with progression from mild cognitive impairment to dementia
(hazard ratios 1.47 and 2.68) and in one of these studies was associated with earlier death (hazard
ratio 1.95). 2 Patients with psychotic symptoms are also more likely to be admitted to a nursing
home. An unresolved question is whether this more rapid progression is simply the result of
greater disease activity or whether it is caused by exposure to treatments for the symptoms,
resulting in a range of severe adverse events that negatively impact the patient’s condition.
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