Subtle cognitive impairment can be detected in early Parkinson's disease (PD). In a consecutive series of de novo, drug-naive PD patients, we applied stepwise regression analysis to assess which clinical, neuropsychological, and functional neuroimaging (dopamine transporter [DAT] and perfusion single photon emission computed tomography [SPECT]) characteristics at baseline was predictive of cognitive decline during an average follow-up time of about 4 years. Decline both in executive (R(2) = 0.54; p = 0.0001) and visuospatial (R(2) = 0.56; p = 0.0001) functions was predicted by the couple of Unified Parkinson's Disease Rating Scale (UPDRS)-III score and caudate dopamine transporter (DAT) uptake in the less affected hemisphere (LAH). Verbal memory and language decline was predicted instead by caudate DAT uptake and brain perfusion in a posterior parieto-temporal area of the less affected hemisphere (R(2) = 0.42; p = 0.0005). No significant effect was shown for age, baseline neuropsychological scores, and levodopa equivalent dose at follow-up. The combined use of clinical structured examination and brain functional assessment by means of dual single photon emission computed tomography imaging appears as a powerful approach to predict cognitive decline in de novo PD patients.
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