Incidence Prevalence and Risk Factors

Estimates of incidence and prevalence of dementia in PD vary widely because of different definitions, methods of ascertainment, and study designs. Prevalence rates of dementia in hospital- or clinic-based cohort studies range from 11% to 22% (123-125), whereas population-based estimates are somewhat higher, ranging from 18% to 44% (9,126-129), perhaps reflecting referral bias. A recent systematic review of the literature estimated that the prevalence of dementia in PD ranges from 25% to 31% (130). This review also found that dementia in PD accounted for 3% to 4% of the total dementia population.

Incidence rates for PD dementia range from 4% to 11% per year, with a relative risk for the development of dementia in PD of 2 to 6 (12,129,131-133). Age and severity of extrapyramidal symptoms were associated with an overall risk of developing dementia. One study demonstrated that age and severity of disease by themselves were not associated with a greater risk of dementia, but the combination of these two features resulted in an almost 10-fold greater risk (134), suggesting a combined effect. Later age of onset of PD, longer duration of PD symptoms, the presence of hallucinations, depressive symptoms, and a family history of dementia have also been reported to be risk factors for dementia, although less consistently.

Although dementia in PD has been traditionally thought of as occurring in the "latter half" of the disease, it may actually parallel motor progression from its onset and is simply recognized much later than the motor symptoms. Fernandez et al. correlated the neuropsychological profiles of 106 random PD patients to the total motor UPDRS "off" scores and found a significant correlation with MMSE and Dementia Rating Scale (DRS) scores (r=-0.34, P < 0 .001; r=-0.34, P < 0.001, respectively). Moreover, certain motor aspects correlated better: bradykinesia and postural/gait dysfunction were most correlated with cognitive function but tremor was not, axial signs also correlated more than appendicular signs, and parkinsonism on the right side correlated more than on the left side (135).

Some common risk factors for the development of AD, including head injury, hypertension, and diabetes mellitus, are not predictors for the development of dementia in PD (136). However, the epsilon 4 isoform of the apolipoprotein E gene (APO-E4), an established risk factor for AD, has been shown to correlate with an increased risk of dementia in PD (12,137,138). Furthermore, the epsilon 2 allele (APO-E2) is also associated with the development of dementia in PD patients (12,137), whereas it is considered protective in AD.

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