Course of dementia and rate of progression

The course of dementia in PD is relentlessly progressive over years—a reversible course has not been observed [37]. At times patients may seem to have been stabilized for months; they may, however, also show episodes of rapid worsening for no obvious reason. Fluctuations during the day and from day to day, as occur in DLB, are also frequent in patients with PD-D. When asked, family members would admit that the patient is clearly better on certain days or at certain times of the day, usually in the morning, and tending to perform worse after a bad night’s sleep. As dementia progresses patients become increasingly more confused, living in almost a continuous confusional state, with prolonged blank stares and signs of visual hallucinations, although these may not be verbalized. Speech and postural problems often worsen in parallel and patients become more and more dependent.

Rate of progression

There have been two studies in which the rate of progression was evaluated prospectively in patients with PD-D, using MMSE as the cognitive measure. In one of these studies patients with PD-D were compared with those with AD and with healthy controls. Over a 4-year period the annualized decline was a mean score of 2.3 in the PD-D group compared with 2.6 in patients with AD; the change in the PD group without dementia was small and similar to that for healthy controls [38]. The annualized decline in the PD-D group was variable across the patients and ranged from 1 (18%) to >4 (16%) points. In the other study, cognitive decline was compared in patients with PD-D, DLB, and controls. Over a 2-year period cognitive decline was a mean score of 4.5 in the PD-D group, 3.9 in the DLB group, 0.2 in the PD group and 0.3 in the controls [39], thus yielding annual rates of decline very similar to those in the previous study. Although these studies provide useful information, they may not reflect the true progression of the disease because MMSE is rather insensitive for the assessment of executive dysfunction, which is one of the core features of PD-D. Indirect evidence as to the rate of progression using other parameters, albeit over a shorter period, can also be deduced from placebo-controlled clinical trials. One such trial, performed in a large PD-D population with mild to moderate dementia, included a sizeable placebo arm. All cognitive and functional measures worsened in the placebo group; the decrease in the MMSE score over a period of 6 months was 0.2 (out of 20 at baseline), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score decreased by 0.7 (out of 24 at baseline), and the Alzheimer Disease Consortium Study activities of daily living (ADL) score decreased by 3.6 (out of 41 at baseline) [40]. These decreases were smaller than those observed in AD patients receiving placebo in clinical studies with a comparable design and duration, suggesting a slower rate of progression in PD-D. Such comparisons, however, have limited value as they are indirect.

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