Neuropsychological Subgroups in Non-Demented Parkinson’s Disease: A Latent Class Analysis

Abstract

Background Methods to detect early cognitive decline and account for heterogeneity of deficits in Parkinson's disease (PD) are needed. Quantitative methods such as latent class analysis (LCA) offer an objective approach to delineate discrete phenotypes of impairment. Objective To identify discrete neurocognitive phenotypes in PD patients without dementia. Methods LCA was applied to a battery of 8 neuropsychological measures to identify cognitive subtypes in a cohort of 199 non-demented PD patients. Two measures were analyzed from each of four neurocognitive domains: executive functioning, memory, visuospatial abilities, and language. Additional analyses examined between-groups differences in demographic and clinical characteristics (Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory [ADCS-ADL]; UPDRS-III; PD subtype (i.e., tremor-dominant (TD) versus postural instability/gait disturbance-dominant(PIGD)); and cognitive diagnosis (i.e., intact cognition versus mild cognitive impairment; MCI). Results LCA identified 3 distinct groups of PD patients: an intact cognition group (n=109; 54.8%), an amnestic group (n=64[32.1%]; impaired recall and recognition on verbal memory tasks, but intact performance on other measures) and a mixed impairment group with dysexecutive, visuospatial and lexical retrieval deficits (n=26 [13.1%]; relative deficits on measures of verbal fluency, visuospatial abilities, and delayed free recall on a memory task, but intact recognition memory). The amnestic and mixed impairment groups had significantly lower ratings of IADL functioning and greater motor symptoms than the cognitively intact group. Additionally, patients with PIGD vs. TD PD subtype were more likely to be classified in either cognitively impaired group. Of those diagnosed as cognitively normal according to MDS criteria (n=151), LCA classified 35 patients as amnestic (23.2%), and 15 as mixed impairment (9.9%). Conclusions Non-demented PD patients exhibit distinct neuropsychological profiles. One-third of patients with LCA-determined impairment were diagnosed as cognitively intact by expert consensus, indicating that classification using a statistical algorithm may assist in detection of early and subtle cognitive decline. This study also demonstrates that memory impairment is common in non-demented PD even when cognitive impairment is not clinically apparent. This study has implications for earlier detection of cognitive difficulties in PD, predicting eventual emergence of significant cognitive decline, and treatment trials for cognitive dysfunction in PD.

Subjective Cognitive Complaint in Parkinson's Disease Patients With Normal Cognition: Canary in the Coal Mine?

“…37,38 However, in PD it is important to emphasize cognitive complaints broadly, rather than a memory complaint specifically, given the range of cognitive deficits that occurs in nondemented patients with PD. 39,40 Executive functioning and attention in particular are reliant on fronto-striatal functioning, which is disrupted initially during the course of PD. 41,42 The findings of the present study suggest that a simple, single clinical question focused on the self-perception of general cognitive changes compared with one's premorbid state may predict future decline in these cognitive domains.…”

Parkinson disease clinical subtypes: key features & clinical milestones

“…6,7 However, cognitive and psychiatric features also contribute to quality of life and may differentiate subtypes. [8][9][10] Thus, multi-domain approaches could have greater clinical utility than single-domain (e.g., motor) classifications.…”

Subtypes of Sleep Disturbance in Parkinson's Disease Based on the Cross-Culturally Validated Korean Version of Parkinson's Disease Sleep Scale-2

“…23 The discrete model fit was assessed based on the interpretability, parsimony of latent classes, Akaike information criterion, and Bayesian information criterion statistics. 12,14 Demographics and clinical differences were compared among identified latent classes using the chisquare test or the Kruskal-Wallis test followed by post-hoc comparisons with Bonferroni-corrected Mann-Whitney U tests, as appropriate. Table 1 presents demographics and clinical data of the 122 patients enrolled in this study.…”

“…Several studies have applied LCA in PD populations to address depression-anxiety subtypes 12,13 and neurocognitive subtypes. 14 The potential causes of sleep disturbances vary widely, and have been suggested to include primary insomnia, depression, rapid-eye-movement sleep-behavior disorder (RBD), restless leg syndrome, nocturnal motor symptoms, antiparkinsonian drug side effects, nocturia, and sleep-related breathing disorders, all of which frequently co-occur. 1,3,4 However, few studies have attempted to empirically outline the clinical heterogeneity of sleep-related problems in patients with PD.…”