Memory Phenotypes In Early, De Novo Parkinson's Disease Patients with Mild Cognitive Impairment

Mattia Siciliano, Rosa De Micco, Andrea Gerardo Russo, Fabrizio Esposito, Valeria Sant'Elia, Lucia Ricciardi, Francesca Morgante, Antonio Russo, Jennifer G. Goldman, Carlo Chiorri, Gioacchino Tedeschi, Luigi Trojano, Alessandro Tessitore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Memory deficits in mild cognitive impairment related to Parkinson's disease (PD-MCI) are quite heterogeneous, and there is no general agreement on their genesis. Objectives: To define memory phenotypes in de novo PD-MCI and their associations with motor and non-motor features and patients’ quality of life. Methods: From a sample of 183 early de novo patients with PD, cluster analysis was applied to neuropsychological measures of memory function of 82 patients with PD-MCI (44.8%). The remaining patients free of cognitive impairment were considered as a comparison group (n = 101). Cognitive measures and structural magnetic resonance imaging-based neural correlates of memory function were used to substantiate the results. Results: A three-cluster model produced the best solution. Cluster A (65.85%) included memory unimpaired patients; Cluster B (23.17%) included patients with mild episodic memory disorder related to a “prefrontal executive-dependent phenotype”; Cluster C (10.97%) included patients with severe episodic memory disorder related to a “hybrid phenotype,” where hippocampal-dependent deficits co-occurred with prefrontal executive-dependent memory dysfunctions. Cognitive and brain structural imaging correlates substantiated the findings. The three phenotypes did not differ in terms of motor and non-motor features, but the attention/executive deficits progressively increased from Cluster A, through Cluster B, to Cluster C. This last cluster had worse quality of life compared to others. Conclusions: Our results demonstrated the memory heterogeneity of de novo PD-MCI, suggesting existence of three distinct memory-related phenotypes. Identification of such phenotypes can be fruitful in understanding the pathophysiological mechanisms underlying PD-MCI and its subtypes and in guiding appropriate treatments.

Original languageEnglish (US)
Pages (from-to)1461-1472
Number of pages12
JournalMovement Disorders
Issue number8
StatePublished - Aug 2023


  • Parkinson's disease
  • cognitive
  • memory
  • mild cognitive impairment
  • non-motor symptoms

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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