Predictors and early signs

Several clinical and demographic features are associated with increased risk for dementia. These are described in detail in the chapter 2; the most important ones will be mentioned here. Among many reported associations three can be singled out: one demographic (age), one related to motor phenotype (PIGD type), and the other cognitive performance at the time of assessment.

Predictors of dementia

As repeatedly confirmed in a number of studies, advanced age and severe motor symptoms are the most significant risk factors for dementia [18, 20, 21]. In a population-based cross-sectional study, dementia was not present in any of the patients aged under 50, whereas 69% of all those aged over 80 had dementia [22]. The combination of old age and severe motor symptoms seems to indicate a particularly bleak prognosis, increasing the risk by almost ten-fold compared with patients who are young and have mild disease [23]. There are certain constellations and clinical vignettes which, when present, render patients more susceptible to developing dementia. One such feature is the motor phenotype. Patients with more symmetrical signs, higher disability and bradykinesia scores, and more impairment of gait and balance are more likely to develop dementia [9]. In contrast, patients with the tremor-predominant subtype are less likely to develop dementia than those who suffer from a PIGD subtype [8]. In a group of patients who were prospectively followed up, those who suffered from a tremor-dominant subtype at baseline had converted to a PIGD- predominant subtype by the time they developed dementia [24].

Performance in neuropsychological tests also provides clues as to the risk of developing dementia. Patients with low overall cognitive scores, mild deficits in executive functions, wordfinding difficulties, mild impairment of memory, poor attentional function, reduced verbal fluency, and impairments in picture completion tests are more likely to develop dementia than those patients with normal cognitive performance [18, 21, 25-27]. Letter and especially semantic fluency tests seem to be particularly sensitive measures, as well as copying a figure of intersecting pentagons [8, 25]. The appearance of visual hallucinations or confusion soon after initiation of dopaminergic medication may also be a harbinger of incipient dementia [28]. The reverse is also true: the main risk factor for appearance of hallucinations in treated PD patients is cognitive impairment [29]. Patients with a diagnosis of mild cognitive impairment (MCI) at the time of examination have a higher risk of developing dementia than those without. In a prospective study, 62% of patients with MCI at baseline converted to dementia as opposed to 20% of those who were cognitively intact. Single-domain non-memory MCI and multiple-domain slightly impaired MCI were associated with a high risk of developing dementia, whereas the amnestic MCI subtype was not; however, the numbers in this latter group were small [30]. In the 10-year follow-up of the CamPaIGN study, which has been designed to prospectively track disease evolution from diagnosis in an unselected population, 46% of patients had developed dementia. Baseline predictors of dementia were age, motor impairment, ‘posterior-cortical’ cognitive deficits, and MAPT genotype [31]. In the Norwegian ParkWest study, 182 patients with incident PD were monitored for 3 years; they were classified as having MCI and received a diagnosis of dementia according to published consensus criteria. Significantly more patients with MCI than without MCI at baseline (27.0 versus 0.7%) progressed to dementia during follow-up. Of those with MCI at baseline, 21.6% had reverted to normal cognition during follow-up. MCI at the 1-year visit was associated with a similar progression rate to dementia and reversion rate to normal cognition. However, among the 22 patients with persistent MCI at baseline and the 1-year visit, 45.5% developed dementia and only two had reverted to normal cognition by the end of study. The authors concluded that MCI at PD diagnosis predicts a highly increased risk for early dementia [32].

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