Nonmotor predictors of Parkinson’s dementia revealed

By Eleanor McDermid, Senior medwireNews Reporter

Researchers have identified nonmotor and nondopaminergic motor features that predict incident dementia in patients with Parkinson’s disease (PD).

These include orthostatic hypotension, impaired colour vision and REM sleep behaviour disorder (RBD), report Ronald Postuma (McGill University, Montreal, Quebec, Canada) and study co-authors.

Their findings are based on a 4.4-year follow-up of 80 PD patients, 27 of whom developed dementia, diagnosed using a battery of tests of executive function, memory and visuospatial ability.

Orthostatic hypotension was an especially strong predictor, with each 10 mmHg drop in systolic blood pressure associated with a 1.84-fold increased likelihood of developing dementia. Patients with a drop greater than 10 mmHg had a 7.30-fold increased risk.

“The mechanism for this striking relationship is unclear”, write the researchers in Neurology.

They found that other autonomic variables, such as urinary and erectile dysfunction, were not associated with dementia, counting against the possibility that autonomic dysfunction per se is a marker of a “diffuse” PD subtype with widespread degeneration. However, the team believes a direct causative effect is possible, saying that “it is plausible that repeated episodes of severe hypotension over years can adversely affect cortical neurons already made vulnerable by synucleinopathy.”

RBD also had a marked effect on the risk of dementia. All but one (96%) of the patients who converted to dementia had RBD at baseline, compared with 40% of those who remained dementia free, giving nearly a 50-fold increased risk associated with RBD.

“It is unclear why this very strong relationship should exist”, say Postuma et al, noting that a causal relationship is unlikely.

Having impaired colour vision was associated with a threefold increased dementia risk, which the team attributes to underlying posterior neurodegeneration. As expected, having mild cognitive impairment at baseline was strongly predictive of subsequent dementia, and patients experiencing hallucinations or illusions also had a significantly increased risk.

There were few predictors among the demographical and motor variables the team studied. One notable predictor was patients’ gait scores on the Unified PD Rating Scale part III; by contrast, tremor, bradykinesia and rigidity were not associated with dementia risk.

“Of importance, gait and postural disturbance are part of the classification of akinetic-rigid vs tremor-predominant disease”, say the researchers, adding that “our study suggests that it may be the gait component of this classification that is the primary driver of dementia risk.”

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