This is the longest prospective study of PD and is based on 136 newly diagnosed community living patients referred by 29 neurologists in Sydney from diverse social and educational backgrounds. The referring neurologists also continued to manage the patients after the initial drug study. The average age at presentation (62 years, range 37–79) was similar to other studies of this period.18, 27 We feel that these patients are representative of the general PD population.
When patients reach the later stages of their disease, physical frailty and cognitive decline mean they can no longer attend hospital clinics and private neurologists. Their extreme disability is therefore a hidden problem. In this group, only 14/30 (47%) still see their neurologist after 20 years. The later disease stages can often last 5 years and so, at their most vulnerable period, patients with PD are often lacking specialist care. Careful adjustment of medication can markedly improve quality of life even for the nursing home patient, for example, reducing cognitive side effects or dyskinesia. An outreach service from health professionals with knowledge of PD would be of value.
It is notable that, although not statistically significant, mortality briefly declines in the early years of treatment then continues to rise with the increasing duration of disease. This presumably reflects disease progression and the appearance of disease features that do not respond to our current medications such as falls, fractures, dysphagia (leading to pneumonia), autonomic failure, and dementia. All of these increase in prevalence after 10 years of disease and are not discussed here, as they formed the basis of the 15-year report.1
Dementia occurred in almost every patient, even in those with a younger onset of disease, who did not succumb to intercurrent disease. The current article includes the whole available group using the neurologist's cognitive assessment to supplement the neuropsychological findings, as not all patients were assessed neuropsychologically. Direct comparison of the neurologist's and neuropsychologist's diagnosis of dementia revealed that neurologists are more likely to underestimate than overestimate the prevalence of dementia in their PD patients as neuropsychological criteria were at times reached before the MMSE fell below 25 or the neurologist was aware of significant decline in social functioning. Neuropsychological assessment early is invaluable in detecting cognitive decline and guiding interventions but is not readily available in the community. Our findings suggest that unless dementia is actively sought and excluded, it should not be assumed to be absent. It is notable that while it is accepted that the MMSE is a poor tool for examining cognitive decline in PD with dementia (PDD), the CDR scale also tended to under-diagnose dementia (usually rating people 0.5, cognitive decline but not dementia) compared to the formal neuropsychological assessment. The latter is taken for the diagnosis of dementia where performed.
Clinical criteria for the diagnosis of PDD have recently been proposed that include the core features of idiopathic PD and a slowly progressive dementia syndrome that includes impairment in more than 1 cognitive domain that is a decline from premorbid levels. Cognitive deficits must be severe enough to impair daily functioning independent of deficits due to motor or autonomic failure.28 Memory loss is not essential for diagnosis unlike DSM IV criteria or as defined in our neuropsychological diagnosis. Although memory loss is noted to occur commonly as the dementia progresses, it is not always an early feature.29 As in our cases, it is clearly of value to have continuity of follow-up to detect the evolution of these changes and to be able to weight the various contributions of cognitive, autonomic, and motor deficits that impair the social, personal, and occupational functioning of people with PD. The history of a carer is also invaluable and delirium from drugs or systemic illness, and major depression need exclusion. Although neuroimaging may show changes of vascular disease in this older population, the typical insidious onset of PDD suggests that this is usually not the major cause. Extreme bradykinesia with poor motor skills and dysarthria can hamper cognitive assessment late in PD. It is, therefore, essential to perform serial brief regular assessments throughout the disease course to detect cognitive decline, and we encourage neurologists to add some of the simple tests used here to their assessments.
The prevalence of dementia in PD is poorly appreciated in the wider neurological community. It behoves neurologists to examine patients with PD most carefully for dementia as it has a number of consequences including: its association with drug and procedure induced hallucinations and psychoses; excessive daytime sleepiness and carer distress; loss of insight and poor judgment; the inability of patients to make sound financial decisions; impairment of driving skills; unreliability in following advice concerning medication; visuospatial problems that contribute to an increased risk of falls and fractures; unsuitability for deep brain stimulation, and it should suggest that elective surgery for intercurrent problems is best avoided. In association with increasing age, dementia and hallucinations predict nursing home placement.1 Although dementia was predictive of death (P = 0.001) univariately, it is so strongly associated with increasing age as to render it insignificant when age is corrected for multivariately.17 When correcting for severity of motor symptoms, Levy et al. found that incident dementia was associated with a doubling of mortality risk in a group of older PD patients.30
Dementia is unusual in younger patients at presentation. At baseline, 8% of patients aged 40 to 69 showed evidence of dementia by neuropsychological criteria. However, dementia was found in 39% of those aged 70 to 79 years at presentation.11 Today, these people would be called DLB, although their presenting symptoms were motor, not dementia or hallucinations. These patients died early and so do not feature in the percentages of demented patients at 15 to 20 years. Others have also noted cognitive impairment in a proportion of patients with early PD.12 The cognitive profile of PDD and DLB is very similar.31 In a group with the early motor signs of PD, the London Brian Bank was unable to distinguish differences in the physical and cognitive signs and drug responsiveness of those with early dementia of DLB and later dementia of PDD.32
We had no patients with dementia in their 40s but 6 became demented in their 50s, including 1 at 53 after 8 years of disease but still alive at 20 years, and 1 at baseline at age 58 who at postmortem had AD and PD with limbic Lewy bodies. Dementia that is in excess of the general population has been noted in 19% of young onset patients (aged less than 40) after a median of 18 years on a telephone interview: 13% of those still aged under 60 and 43% of those aged over 60.10 In contrast, 83% of our patients are demented after 20 years with an average age now of 74. The strong relationship to age, also noted by others,8, 33, 34 rather than disease duration suggests that additional pathology to Lewy body parkinsonism may have a role in the appearance of dementia. A combination of pathologies is likely to be additive and thus cross the threshold for expression of dementia at an earlier stage than a single disease.
The neuropathology of dementia in PD is heterogeneous.35–38 Staining for cortical Lewy bodies with α-synuclein suggests that limbic and cortical Lewy bodies are the most important association of dementia in PD with or without additional Alzheimer's pathology.37, 39 However, the picture is complicated by the fact that neocortical Lewy body involvement does not always correlate with dementia in PD,32 although high numbers of temporal and parahippocampal Lewy bodies may be better correlates of dementia in PD40; and the suggestion that Lewy body inclusions may represent a protective mechanism.41 The fundamental cause of clinical dysfunction in PDD may lie within as yet undiscovered cellular mechanisms.32
In PDD, treatment is limited. Dopaminergic medication is frequently restricted by the appearance of visual hallucinations. Cholinergic deficits from the nucleus basalis of Meynert are believed to contribute to the fluctuations in levels of alertness in DLB42 and cortical cholinergic loss is found to be more severe in PD than in AD.43 This may explain the mild benefit noted in PDD from rivastigmine.44, 45