Psychiatry of Parkinson's Disease

K. P. Ebmeier, J. T. O'Brien, J. -P. Taylor, K.P., Ebmeier, J.T., O'Brien, J.-P., Taylor, W. P. Kaschka, W. F. Gattaz, W.P., Kaschka, W.F., Gattaz

• Publisher: S. Karger
• Year: 2012
• Print ISBN: 9783805598002
• eBook ISBN: 9783805598019
• Topic: Medicine
• Subtopic: Geriatrics

Psychiatric symptoms are common in the neurological and geriatric care of patients with Parkinson's disease. This book assembles short reviews from experts in the field to chart the various psychiatric syndromes known in Parkinson's disease, their presentation, etiology and management. Presented are special topics on epidemiology of psychiatric symptoms, affective disorders and apathy, early cognitive impairment through to dementia, visuoperceptual dysfunction, psychotic disorders, sleep disturbances, impulse disorders and sexual problems. Further, rarely discussed issues, such as the relationship between somatoform disorders and parkinsonism are reviewed. This publication is essential reading for old age psychiatrists, gerontologists and neurologists who work with patients suffering from Parkinson's disease. In addition, health practitioners who deal with senior patients, as well as scientists who need a quick update on the progress in this important clinical field will find this volume a helpful reference.

Ebmeier KP, O’Brien JT, Taylor J-P (eds): Psychiatry of Parkinson’s Disease.
Adv Biol Psychiatry. Basel, Karger, 2012, vol 27, pp 103-124

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Parkinson’s Disease with Dementia

John-Paul Taylor · John T. O’Brien

Institute for Ageing and Health, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne, UK

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Abstract

Parkinson’s disease with dementia (PDD) is now recognised as a major clinical consequence of idiopathic Parkinson’s disease (PD). Indeed the cumulative prevalence of dementia in PD is very high; up to 80% of patients will develop dementia within 10 years of their Parkinson’s diagnosis. The consequences of PDD, including the associated neuropsychiatric, autonomic and sleep symptoms, are profound. With increased survival in PD accurate diagnosis and appropriate management of PDD in neurological, movement disorder and psychiatric services is increasingly important. In this chapter we explore the epidemiology of PDD, risk factors for its development as well as clinical features, diagnostic issues, prognosis and management. We conclude with a synthesis of current theoretical considerations and research into the aetiology of PDD.

Copyright © 2012 S. Karger AG, Basel

An Essay on the Shaking Palsy by James Parkinson is remarkable in its inclusive and thorough description of the motor symptoms of Parkinson’s disease (PD) [1]. However he stated that it was a condition which left the ‘senses and intellects’ ‘uninjured’, and this belief was perpetuated for a significant part of the 20th century.

However perhaps consequent to the development of dopaminergic treatment and increased survival of PD patients, it has now become increasingly recognised that cognitive and neuropsychiatric dysfunction is an integral part of PD. Indeed there is now evidence to indicate that the majority of people with PD will develop so-called Parkinson’s disease with dementia (PDD) within 10 years of diagnosis [2]. Furthermore with the spotlight of modern enquiry, including genetic, neuroimaging and detailed neuropsychological studies, subtle deficits have been observed even in the earliest stages of PD (see chapter 10 for further elaboration).

There is now also a convergence of opinion [3] that PDD shares a common aetiological basis with a closely related condition, dementia with Lewy bodies (DLB) but that they represent different points along a Lewy body disease spectrum. DLB was defined on the basis of people presenting primarily with dementia, who had varying degrees of parkinsonism (often falling short of full PD) and who had alphasynuclein (Lewy body) pathology at autopsy. Traditionally DLB and PDD have been separated on clinical grounds, though clinical, imaging, cognitive, therapeutic and pathological studies suggest considerable overlap between DLB and PDD. Indeed both PDD and DLB are now often collectively referred as the Lewy body dementias (LBDs). In this chapter, we focus on PDD, although we draw upon evidence and data from studies in DLB as appropriate. We explore the epidemiology of diagnostic classification and neuropsychiatric features of PDD as well as briefly cover management of this complex condition. We conclude with a discussion on the proposed aetiology including neuropathological findings and recent genetic determinations. Interest in PDD has burgeoned over the past decade [4], and there is now a significant literature on the condition. This chapter thus provides more of a taster for the reader rather than an exhaustive text; for example, we do not discuss recent innovative developments in LBD biomarkers, as this is beyond the scope of this chapter, but would refer the reader to reviews such as Burn [5] and Johansen et al. [6] on the subject. For an in-depth exploration of all aspects concerning PDD, we would suggest Emre [7], which provides a comprehensive clinical and research overview of PDD. A similarly structured text edited by O’Brien et al. [8] provides a detailed description of DLB.

Epidemiology of Parkinson’s Disease with Dementia

Prevalence and incidence rates of PDD have varied depending upon the methodologies applied in particular surveys, imprecision in definitions of dementia and cognitive impairment, as well as pathological heterogeneity in the patient populations studied. Nevertheless a comprehensive recent systematic review [9] of the available literature found a mean point prevalence of 31.3% (29.2– 33.6 95% confidence interval) of dementia in PD patients, with community prevalence of PDD in the over 65s between 0.3 and 0.5%.

As discussed in chapter 10, it is becoming increasingly recognised that cognitive impairment is present even in the earliest stages of PD; for example, it was shown that between 19 and 24% of newly diagnosed PD patients had a mild degree of cognitive impairment [10, 11]. These deficits appear to progress over time, and it has been suggested that the mean duration from onset of PD to the development of PDD is around 10 years. A longitudinal study based in Norway suggested that the cumulative prevalence was up to 78% after 8 years of follow-up [2]. Consistent with this are the incidence rates of PDD from longitudinal community-based cohorts which are at least four to six times that of the rate of dementia in age-matched controls with approximately 10% of PD patients developing dementia annually [9, 12].

A variety of risk factors for the development of dementia in PD have been described, and these are summarised in table 1.

Table 1. Risk factors for PDD

Risk factor	Comments
Age	This is a major risk factor for PDD; it may play a major role in aetio-pathology of PDD by interacting with disease processes in non-dopaminergic structures [13].
Parkinsonism	The severity of motor manifestations, in particular, the symptoms of rigidity, and the so-called postural instability gait disorder (PIGD), appear particularly important [14–17].
Gender	PD incidence is twice as common in men as women, but it is not clear if male gender predisposes PD patients to the development of PDD.
Pre-existing mild cognitive impairment	Individuals with mild cognitive impairment at diagnosis of PD are at greater risk of subsequent development of dementia, although those with amnestic mild cognitive impairment do not. See chapter 10 for further elaboration.
Neuropsychiatric symptoms	Neuropsychiatric symptoms in general [18–20] are associated with cognitive impairment in PD. Specific associations with cognitive impairment and dementia include depression and visual hallucinations; the former may be a prodrome of PDD [21] while the latter associated with a much higher rate of cognitive decline and greater risk of dementia in PD. Common underlying aetio-pathologies may contribute to both the neuropsychiatric symptom and cognitive dysfunction; for example, there is an association between cortical Lewy body disease in the temporal lobe with visual hallucinations and dementia [22].
Genetics	Family history of PD does appear to increase the risk of dementia in PD [23]. The presence of apolipoprotein E4 genotype, unlike AD, does not appear to increase the risk for PDD development [24–27]. However MAPT gene with H1/ H1 haplotype may be a risk factor. Gene-dose effect with triplication of the associated alpha-synuclein gene has been suggested to give rise to familial variants of PDD, whereas duplication is associated with motor PD alone [28]. Recent autopsy studies have demonstrated that 4–10% of PD patients have evidence for glucocerebrosidase (GBA) mutations. GBA deficiency arising as a result of an autosomal recessive mutation is more typically thought of as the cause of Gaucher’s disease. However it has recently been suggested that GBA mutations represent the most common genetic risk factor for the development of PD or LBDs [29] in Lewy body dementias although this finding needs confirmation.
Smoking	Whether smoking is protective or risk factor for the development of PDD is not clear as longitudinal findings have been contradictory [24, 30].

Diagnostic Classification of Parkinson’s Disease with Dementia

Consensus operational criteria for PDD [31] have recently been developed (see tables 2 and 3), which take account of the constellation of signs and symptoms that are prototypical to PDD. The criteria make two major diagnostic separations: probable PDD and possible PDD. For a diagnosis of either, the presence of core symptoms of (1) diagnosis of parkinsonism, (2) a dementia with an insidious onset and slow progression in the context of established PD, and (3) the absence of features which could suggest other conditions as the cause of mental impairment is required (e....

Table of contents

• Cover Page
• Front Material
• Epidemiology of Psychiatric Symptoms in Parkinson's Disease
• Depression, Apathy and Anxiety Disorders
• Apathy in Parkinson's Disease
• Disorders of Visual Perception in Parkinson's Disease and Other Lewy Body Disorders
• Psychosis and Parkinson's Disease
• Sleep in Parkinson's Disease and Dementia with Lewy Bodies
• Sexual Problems in Parkinson's Disease
• An Update on Impulse Control Disorders in Parkinson's Disease
• Neuropsychological Features of Early Cognitive Impairment in Parkinson's Disease
• Parkinson’s Disease with Dementia
• Somatoform Disorders in Parkinson’s Disease and Dementia with Lewy Bodies Evidence Underlying Psychotic Traits
• Drug-Induced Parkinsonism and Abnormal Involuntary Movements
• Author Index
• Subject Index