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. 2024 Jun 11;16(3):1754-1768.
doi: 10.14336/AD.2024.0553.

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

Giovanni Palermo  1 , Sara Giannoni  1 , Luca Tommasini  1 , Gabriele Bellini  1 , Daniela Frosini  1 , Gayane' Aghakhanyan  2 , Riccardo Morganti  3 , Duccio Volterrani  2 , Nicola Pavese  4   5 , Roberto Ceravolo  1
Affiliations

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

Giovanni Palermo et al. Aging Dis. .

Abstract

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.

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Conflict of interest statement

We guarantee that patients have given their consent to anonymously report their clinical reports in accordance with current ethical standards. A specific IRB approval was not required to carry out the analysis presented in this paper. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines report concerning the research related to the manuscript.

Figures

Figure 1.
Figure 1.
Effects of age: comparison of [123I]FP-CIT binding values between PD and HC in the putamen (A) and caudate (B).
Figure 2.
Figure 2.
Effects of age on C/P (Caudate/putamen) ratio in PD (A) and HC (B).
Figure 3.
Figure 3.
Scatterplot showing association between age at PD onset and UPDRS III score (on the left), and between age at PD onset and measures of general cognitive function (Mini-Mental State Examination -MMSE- and Frontal Assessment Battery -FAB-) (on the right).
Figure 4.
Figure 4.
Scatterplot showing association between baseline [123I]FP-CIT SPECT binding values in the caudate and cognitive scores.
See this image and copyright information in PMC

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