Factor analysis–derived cognitive profile predicting early dementia conversion in PD

Chung, Seok Jong; Lee, Hye Sun; Kim, Hang Rai; Yoo, Hyung Sik; Lee, Yang Hyun; Jung, Jin Ho; Baik, Kyoung Won; Ye, Byoung Seok; Sohn, Young H.; Lee, Phil Hyu

doi:10.1212/wnl.0000000000010347

Cited by 29 publications

(72 citation statements)

References 46 publications

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“…The CamPaIGN study found that posterior cortical defi cits were closely related to incident dementia in PD 41 . Meanwhile, other studies showed that frontal/executive dysfunction and frontal atrophy were associated with a higher risk for dementia conversion [42][43][44] . The discrep ancies might be ascribed to different genetic or eth nic backgrounds.…”

Section: Risk Factorsmentioning

confidence: 99%

Parkinson disease-associated cognitive impairment

Aarsland

Batzu

Halliday

et al. 2021

Nat Rev Dis Primers

579

417

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Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment.

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Section: Risk Factorsmentioning

confidence: 99%

Parkinson disease-associated cognitive impairment

Aarsland

Batzu

Halliday

et al. 2021

Nat Rev Dis Primers

579

417

View full text Add to dashboard Cite

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“…Interestingly, VN-FPN connectivity increased over 1 year in a mixed PDCN/PDMCI cohort, but not healthy controls ( Klobusiakova et al, 2019 ), and did not correlate with cognition. Our finding indicates this internetwork coupling topology is an early signature of high-level visual disturbances in PD ( Weil et al, 2016 ), which is of keen interest as early visuospatial decline is a risk for MCI and dementia ( Williams-Gray et al, 2013 ; Hong et al, 2014 ; Hobson and Meara, 2015 ; Garcia-Diaz et al, 2018 ; Chung et al, 2020 ; Ohdake et al, 2020 ).…”

Section: Discussionmentioning

confidence: 66%

Internetwork Connectivity Predicts Cognitive Decline in Parkinson’s and Is Altered by Genetic Variants

Wei

Shen

Litvan

et al. 2022

Front. Aging Neurosci.

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In Parkinson’s disease (PD) functional changes in the brain occur years before significant cognitive symptoms manifest yet core large-scale networks that maintain cognition and predict future cognitive decline are poorly understood. The present study investigated internetwork functional connectivity of visual (VN), anterior and posterior default mode (aDMN, pDMN), left/right frontoparietal (LFPN, RFPN), and salience (SN) networks in 63 cognitively normal PD (PDCN) and 43 healthy controls who underwent resting-state functional MRI. The functional relevance of internetwork coupling topologies was tested by their correlations with baseline cognitive performance in each group and with 2-year cognitive changes in a PDCN subsample. To disentangle heterogeneity in neurocognitive functioning, we also studied whether α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) variants alter internetwork connectivity and/or accelerate cognitive decline. We found that internetwork connectivity was largely preserved in PDCN, except for reduced pDMN-RFPN/LFPN couplings, which correlated with poorer baseline global cognition. Preserved internetwork couplings also correlated with domain-specific cognition but differently for the two groups. In PDCN, stronger positive internetwork coupling topologies correlated with better cognition at baseline, suggesting a compensatory mechanism arising from less effective deployment of networks that supported cognition in healthy controls. However, stronger positive internetwork coupling topologies typically predicted greater longitudinal decline in most cognitive domains, suggesting that they were surrogate markers of neuronal vulnerability. In this regard, stronger aDMN-SN, LFPN-SN, and/or LFPN-VN connectivity predicted longitudinal decline in attention, working memory, executive functioning, and visual cognition, which is a risk factor for dementia. Coupling strengths of some internetwork topologies were altered by genetic variants. PDCN carriers of the SNCA risk allele showed amplified anticorrelations between the SN and the VN/pDMN, which supported cognition in healthy controls, but strengthened pDMN-RFPN connectivity, which maintained visual memory longitudinally. PDCN carriers of the MAPT risk allele showed greater longitudinal decline in working memory and increased VN-LFPN connectivity, which in turn predicted greater decline in visuospatial processing. Collectively, the results suggest that cognition is maintained by functional reconfiguration of large-scale internetwork communications, which are partly altered by genetic risk factors and predict future domain-specific cognitive progression.

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“…Baseline neuropsychological profile in early-stage PD may predict the risk of developing dementia. Factor analysis in a previous study [ 22 ] demonstrated that the composite of executive, visuospatial and verbal memory deficits was associated with a higher risk of dementia conversion. Among them, frontal/executive dysfunction contributed most to the occurrence of PDD [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Factor analysis in a previous study [ 22 ] demonstrated that the composite of executive, visuospatial and verbal memory deficits was associated with a higher risk of dementia conversion. Among them, frontal/executive dysfunction contributed most to the occurrence of PDD [ 22 ]. The consistency with previous results allows us to confirm the value of MoCA-BC in assessing MCI in Chinese PD patients.…”

Section: Discussionmentioning

confidence: 99%

Application of the Chinese Version of the Montreal Cognitive Assessment-Basic for Assessing Mild Cognitive Impairment in Parkinson’s Disease

Zhou

Jiang

et al. 2021

Brain Sciences

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Mild cognitive impairment (MCI) is a common and pivotal non-motor symptom in Parkinson’s disease (PD). It is necessary to use the appropriate tools to characterize the cognitive profiles and identify the subjects at risk of MCI in clinical practice. A cohort of 207 non-demented patients with PD and 52 age- and gender-matched cognitively normal controls (NCs) underwent the Chinese Version of Montreal Cognitive Assessment-Basic (MoCA-BC) evaluation. Patients with PD also received detailed motor and non-motor evaluation by serial scales. Cognitive profiles were investigated in patients with PD-MCI, relative to patients with normal cognition (PD-NC) and cognitively NCs. In addition, differences in demography, major motor and non-motor symptoms were compared between patients with PD-MCI and PD-NC. There were 70 patients with PD-MCI, occupying 33.8% of the total patients. Patients with PD-MCI had impairment in multiple cognitive domains, especially in executive function, memory and visuospatial function on MoCA-BC, relative to cognitively NCs or PD-NC. Compared with PD-NC patients, PD-MCI patients were older (p = 0.002) and had a later onset age (p = 0.007) and higher score of the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (p = 0.001). The positive rate of clinical possible rapid eye movement sleep behavior disorder (cpRBD) in the PD-MCI group was significantly increased relative to the PD-NC group (p = 0.003). Multivariate logistic analysis showed that older age (OR = 1.06; p = 0.012), higher score of UPDRS-III (OR = 1.03; p = 0.018) and the presence of cpRBD (OR = 2.10; p = 0.037) were independently associated factors of MCI in patients with PD. In conclusion, executive function, memory and visuospatial function are the main impaired cognitive profiles in PD-MCI via MoCA-BC. Aging, motor severity and RBD may be independently related factors of MCI in PD.

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Factor analysis–derived cognitive profile predicting early dementia conversion in PD

Cited by 29 publications

References 46 publications

Parkinson disease-associated cognitive impairment

Parkinson disease-associated cognitive impairment

Internetwork Connectivity Predicts Cognitive Decline in Parkinson’s and Is Altered by Genetic Variants

Application of the Chinese Version of the Montreal Cognitive Assessment-Basic for Assessing Mild Cognitive Impairment in Parkinson’s Disease

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