Exploring the Distinct Effect of Age at Onset and Caudate Denervation on Cognitive Deficits in Early Parkinson’s Disease

TY - JOUR

T1 - Exploring the Distinct Effect of Age at Onset and Caudate Denervation on Cognitive Deficits in Early Parkinson’s Disease

AU - Palermo, Giovanni

AU - Giannoni, Sara

AU - Tommasini, Luca

AU - Bellini, Gabriele

AU - Frosini, Daniela

AU - Aghakhanyan, Gayane

AU - Morganti, Riccardo

AU - Volterrani, Duccio

AU - Pavese, Nicola

AU - Ceravolo, Roberto

N1 - Publisher Copyright: © 2024 Palermo G. et al.

PY - 2025/6

Y1 - 2025/6

N2 - Older age at onset and baseline caudate dopaminergic denervation are recognized risk factors for cognitive impairment in Parkinson’s disease (PD), posing challenges in identifying their relative contribution to cognitive outcomes. The objective of this study was to assess the distinct contribution of age at onset and baseline caudate dopaminergic binding to the early cognitive deficits in PD patients. We examined the relationship between baseline dopaminergic striatal dysfunction (measured using [123I]-FP-CIT SPECT), age at disease onset and neuropsychological performance in 128 drug-naive PD patients, utilizing putaminal and caudate binding values of 77 healthy controls (HC) for a comparative exploration of age-dependent loss of DAT availability. Additionally, we investigated whether age at onset and DAT binding value of the caudate could independently predict cognitive changes over a median of 7-year follow-up. [123I]-FP-CIT-SPECT binding values had a significant negative correlation with age in both PD and HC, but in PD, aging was linked with a steeper slope for the caudate than the putamen. Older age at onset and lower caudate uptake were associated with worse global cognitive function and performance in specific neuropsychological tests at baseline and demonstrated to be significant independent predictors of cognitive dysfunction at follow-up. Our findings confirm a differential age effect on [123I]-FP-CIT binding in the striatal subregions of de novo PD patients. Notably, we found less age-related attrition of dopaminergic binding in the putamen than in the caudate, reflecting likely the superimposition of putaminal compensatory mechanisms and an increased predisposition of old onset PD patients to develop cognitive disturbances.

AB - Older age at onset and baseline caudate dopaminergic denervation are recognized risk factors for cognitive impairment in Parkinson’s disease (PD), posing challenges in identifying their relative contribution to cognitive outcomes. The objective of this study was to assess the distinct contribution of age at onset and baseline caudate dopaminergic binding to the early cognitive deficits in PD patients. We examined the relationship between baseline dopaminergic striatal dysfunction (measured using [123I]-FP-CIT SPECT), age at disease onset and neuropsychological performance in 128 drug-naive PD patients, utilizing putaminal and caudate binding values of 77 healthy controls (HC) for a comparative exploration of age-dependent loss of DAT availability. Additionally, we investigated whether age at onset and DAT binding value of the caudate could independently predict cognitive changes over a median of 7-year follow-up. [123I]-FP-CIT-SPECT binding values had a significant negative correlation with age in both PD and HC, but in PD, aging was linked with a steeper slope for the caudate than the putamen. Older age at onset and lower caudate uptake were associated with worse global cognitive function and performance in specific neuropsychological tests at baseline and demonstrated to be significant independent predictors of cognitive dysfunction at follow-up. Our findings confirm a differential age effect on [123I]-FP-CIT binding in the striatal subregions of de novo PD patients. Notably, we found less age-related attrition of dopaminergic binding in the putamen than in the caudate, reflecting likely the superimposition of putaminal compensatory mechanisms and an increased predisposition of old onset PD patients to develop cognitive disturbances.

KW - age

KW - caudate

KW - cognitive deficits

KW - dopamine transporter

KW - Parkinson’s disease

UR - http://www.scopus.com/inward/record.url?scp=105007179012&partnerID=8YFLogxK

U2 - 10.14336/AD.2024.0553

DO - 10.14336/AD.2024.0553

M3 - Journal article

C2 - 39226163

AN - SCOPUS:105007179012

SN - 2152-5250

VL - 16

SP - 1754

EP - 1768

JO - Aging and Disease

JF - Aging and Disease

IS - 3

ER -