Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson's Disease Psychosis

Sara Pisani; Latha Velayudhan; Dag Aarsland; Kallol Ray Chaudhuri; Clive Ballard; Dominic Ffytche; Sagnik Bhattacharyya

doi:10.1136/bmjment-2024-301430

Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson's Disease Psychosis

Sara Pisani, Latha Velayudhan, Dag Aarsland, Kallol Ray Chaudhuri, Clive Ballard, Dominic Ffytche, Sagnik Bhattacharyya

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Cognitive deficits and reduced dopamine transporter (DAT) binding ratio have been reported in Parkinson's disease psychosis (PDP). However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP.

OBJECTIVES: We examined this using data from the Parkinson's Progression Markers Initiative.

METHODS: We analysed data from 392 PD patients, from baseline to year 4 follow-up, and classified patients into PD with psychosis (PDP) and without psychosis (PDnP). DAT SBR was available from 123I-FP-CIT-SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging. We examined all cognitive measures assessed at each time point; sociodemographic characteristics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest.

FINDINGS: PDP patients had lower DAT SBR compared with PDnP patients (b=-0.092, p=0.035) over all time points, which remained significant after controlling for age, sex and ethnicity. PDP patients also reported worse trajectory of task performance on the Montreal Cognitive Assessment (MoCA) (b=-0.238, p=0.001) and symbol digit modality (b=-0.534, p=0.016) compared with PDnP patients. Declining performance in symbol digit modality (Group×Time×DAT SBR interaction, b=0.683, p=0.028) but not MoCA was differentially associated with the decline in DAT SBR over time. MoCA scores declined more in PDP compared with PDnP patients over all timepoints (Group×Time interaction, b=-0.284, p=0.016).

CONCLUSIONS: Decline in striatal presynaptic dopamine function may specifically underlie longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.

Original language	English
Article number	301430
Journal	BMJ mental health
Volume	28
Issue number	1
DOIs	https://doi.org/10.1136/bmjment-2024-301430
Publication status	Published - 31 Mar 2025

Keywords

Humans
Parkinson Disease/metabolism
Male
Female
Aged
Psychotic Disorders/metabolism
Middle Aged
Tomography, Emission-Computed, Single-Photon
Dopamine Plasma Membrane Transport Proteins/metabolism
Cognitive Dysfunction/metabolism
Corpus Striatum/metabolism
Neuropsychological Tests
Tropanes/pharmacokinetics
Disease Progression

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@article{7ef20620aacd4a658bd877b71f826660,

title = "Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson's Disease Psychosis",

abstract = "BACKGROUND: Cognitive deficits and reduced dopamine transporter (DAT) binding ratio have been reported in Parkinson's disease psychosis (PDP). However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP.OBJECTIVES: We examined this using data from the Parkinson's Progression Markers Initiative.METHODS: We analysed data from 392 PD patients, from baseline to year 4 follow-up, and classified patients into PD with psychosis (PDP) and without psychosis (PDnP). DAT SBR was available from 123I-FP-CIT-SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging. We examined all cognitive measures assessed at each time point; sociodemographic characteristics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest. FINDINGS: PDP patients had lower DAT SBR compared with PDnP patients (b=-0.092, p=0.035) over all time points, which remained significant after controlling for age, sex and ethnicity. PDP patients also reported worse trajectory of task performance on the Montreal Cognitive Assessment (MoCA) (b=-0.238, p=0.001) and symbol digit modality (b=-0.534, p=0.016) compared with PDnP patients. Declining performance in symbol digit modality (Group×Time×DAT SBR interaction, b=0.683, p=0.028) but not MoCA was differentially associated with the decline in DAT SBR over time. MoCA scores declined more in PDP compared with PDnP patients over all timepoints (Group×Time interaction, b=-0.284, p=0.016).CONCLUSIONS: Decline in striatal presynaptic dopamine function may specifically underlie longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.",

keywords = "Humans, Parkinson Disease/metabolism, Male, Female, Aged, Psychotic Disorders/metabolism, Middle Aged, Tomography, Emission-Computed, Single-Photon, Dopamine Plasma Membrane Transport Proteins/metabolism, Cognitive Dysfunction/metabolism, Corpus Striatum/metabolism, Neuropsychological Tests, Tropanes/pharmacokinetics, Disease Progression",

author = "Sara Pisani and Latha Velayudhan and Dag Aarsland and {Ray Chaudhuri}, Kallol and Clive Ballard and Dominic Ffytche and Sagnik Bhattacharyya",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC.",

year = "2025",

month = mar,

day = "31",

doi = "10.1136/bmjment-2024-301430",

language = "English",

volume = "28",

journal = "BMJ mental health",

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TY - JOUR

T1 - Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson's Disease Psychosis

AU - Pisani, Sara

AU - Velayudhan, Latha

AU - Aarsland, Dag

AU - Ray Chaudhuri, Kallol

AU - Ballard, Clive

AU - Ffytche, Dominic

AU - Bhattacharyya, Sagnik

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC.

PY - 2025/3/31

Y1 - 2025/3/31

N2 - BACKGROUND: Cognitive deficits and reduced dopamine transporter (DAT) binding ratio have been reported in Parkinson's disease psychosis (PDP). However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP.OBJECTIVES: We examined this using data from the Parkinson's Progression Markers Initiative.METHODS: We analysed data from 392 PD patients, from baseline to year 4 follow-up, and classified patients into PD with psychosis (PDP) and without psychosis (PDnP). DAT SBR was available from 123I-FP-CIT-SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging. We examined all cognitive measures assessed at each time point; sociodemographic characteristics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest. FINDINGS: PDP patients had lower DAT SBR compared with PDnP patients (b=-0.092, p=0.035) over all time points, which remained significant after controlling for age, sex and ethnicity. PDP patients also reported worse trajectory of task performance on the Montreal Cognitive Assessment (MoCA) (b=-0.238, p=0.001) and symbol digit modality (b=-0.534, p=0.016) compared with PDnP patients. Declining performance in symbol digit modality (Group×Time×DAT SBR interaction, b=0.683, p=0.028) but not MoCA was differentially associated with the decline in DAT SBR over time. MoCA scores declined more in PDP compared with PDnP patients over all timepoints (Group×Time interaction, b=-0.284, p=0.016).CONCLUSIONS: Decline in striatal presynaptic dopamine function may specifically underlie longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.

AB - BACKGROUND: Cognitive deficits and reduced dopamine transporter (DAT) binding ratio have been reported in Parkinson's disease psychosis (PDP). However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP.OBJECTIVES: We examined this using data from the Parkinson's Progression Markers Initiative.METHODS: We analysed data from 392 PD patients, from baseline to year 4 follow-up, and classified patients into PD with psychosis (PDP) and without psychosis (PDnP). DAT SBR was available from 123I-FP-CIT-SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging. We examined all cognitive measures assessed at each time point; sociodemographic characteristics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest. FINDINGS: PDP patients had lower DAT SBR compared with PDnP patients (b=-0.092, p=0.035) over all time points, which remained significant after controlling for age, sex and ethnicity. PDP patients also reported worse trajectory of task performance on the Montreal Cognitive Assessment (MoCA) (b=-0.238, p=0.001) and symbol digit modality (b=-0.534, p=0.016) compared with PDnP patients. Declining performance in symbol digit modality (Group×Time×DAT SBR interaction, b=0.683, p=0.028) but not MoCA was differentially associated with the decline in DAT SBR over time. MoCA scores declined more in PDP compared with PDnP patients over all timepoints (Group×Time interaction, b=-0.284, p=0.016).CONCLUSIONS: Decline in striatal presynaptic dopamine function may specifically underlie longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.

KW - Humans

KW - Parkinson Disease/metabolism

KW - Male

KW - Female

KW - Aged

KW - Psychotic Disorders/metabolism

KW - Middle Aged

KW - Tomography, Emission-Computed, Single-Photon

KW - Dopamine Plasma Membrane Transport Proteins/metabolism

KW - Cognitive Dysfunction/metabolism

KW - Corpus Striatum/metabolism

KW - Neuropsychological Tests

KW - Tropanes/pharmacokinetics

KW - Disease Progression

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U2 - 10.1136/bmjment-2024-301430

DO - 10.1136/bmjment-2024-301430

M3 - Article

C2 - 40164470

SN - 2755-9734

VL - 28

JO - BMJ mental health

JF - BMJ mental health

IS - 1

M1 - 301430

ER -

Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson's Disease Psychosis

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