Several Factors May Predict Cognitive Decline in Parkinson’s Disease

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old man depression
Dopamine deficiency, decreases in cortical thickness and volume in certain areas of the brain was predictive of cognitive decline.

Researchers have identified several possible biomarkers of cognitive impairment in patients with Parkinson’s disease (PD), according to findings published in PLOS One. These included global atrophy, Alzheimer’s pathology, genetic factors, and decreased dopamine in certain areas of the brain.1

Up to 80% of patients with PD develop cognitive impairment across multiple cognitive domains. Cognitive decline in PD is most commonly attributed to cortical Lewy body disease, but Alzheimer’s disease has been tied to cognitive impairment in PD as well. Further, several risk factors for cognitive decline in PD have been identified, such as age; sex; and subtypes of PD; genetic factors such as apolipoprotein E4, brain-derived neurotrophic factor (BDNF); and diffuse gray matter atrophy.

To better understand biomarkers for early cognitive decline in PD, investigators led by Daniel Weintraub, MD, of the University of Pennsylvania in Philadelphia, analyzed data from the prospective, longitudinal, Parkinson’s Progression Markers Initiative (PPMI).

The study included 423 patients with a recent diagnosis of idiopathic PD who were followed for up to 3 years. At the time of enrollment, participants were not treated for PD, did not have a dementia diagnosis, and had decreased dopamine transmission (DaT) on imaging. Potentially predictive biomarkers included structural magnetic resonance imaging (MRI), diffusion tensor imaging, cerebrospinal fluid analysis for amyloid beta, and PD-associated single nucleotide polymorphisms (SNPs).

Cognition was assessed annually with the Montreal Cognitive Assessment (MoCA) test along with tests to assess memory, visuospatial, processing speed, executive function, and working memory domains. A MoCA score <26 was set as the cutoff for cognitive impairment.

Overall, the mean MoCA score decreased by approximately 1 point on average during the 3-year follow-up. This was associated with an increase from 22% to 37% in cognitive impairment and an increase from 1% to 6% in dementia diagnoses.

The biomarkers assessed at baseline did not predict cognitive impairment over time with the exception of participants who demonstrated decreased superior temporal lobe (P =.004) and decreased entorhinal (P =.007) thickness on MRI. Likewise, follow-up DaT imaging did not predict cognitive impairment. However, MRI imaging that showed decreased volumes in specific areas of the brain was predictive of a decrease in MoCA scores to less than 26 over time.

After multivariate analysis, biomarkers associated with the prediction of cognitive impairment in patients with PD included dopamine deficiency as evidenced by decreased putamen and caudate DaT; diffuse decrease in cortical volume or thickness in the frontal, temporal, parietal, and occipital lobes on MRI; decreased CSF Aβ 1-42 concerning for Alzheimer’s disease pathology; and BDNF val/val and COMT val/val genes.

The study’s generalizability was limited by the cohort consisting mostly of white, educated participants and only half or participants having a “research quality MRI scan.”  

“Cognitive decline in early PD is independently predicted by multiple biomarker changes, including nigrostriatal dopamine system deficits, wide-ranging atrophy consistent with cortical neurodegenerative disease, evidence for comorbid AD pathology, and genetic factors,” the investigators concluded.

Disclosures: The investigators report multiple disclosures. Please see the study for a full list of disclosures. 

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Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS ONE. 2017;12(5):e0175674. doi: 10.1371/journal.pone.0175674.