Temporal Atrophy Predicts the Deterioration of Cognition in Multiple Domains: a Longitudinal Clinical Study in Parkinson’s Disease
Cheng Zhou1, Xiaojun Guan1, Tao Guo1, and Minming Zhang1

1Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, HangZhou, China


To specify the critical structural alterations of cognitive deterioration in Parkinson’s disease (PD) and explored the underlying mechanism of structural changes. We combined cross-sectional and longitudinal VBM analyses to explore the structural topologies between PD patient who convert to mild cognitive impairment (PD converter). The relationships between dopamine transporter (DAT), CSF proteins and structural alterations were assessed. PD converters showed progressive temporal atrophy associated with multiple cognitive domains. DAT results were significantly associated with temporal atrophy. In conclusion, temporal lobe is a crucial node in modulating cognitive status in multi-domains. Dopamine deficiency may contribute to cognition-related temporal atrophy.


Cognitive impairment is a common symptom in the trajectory of Parkinson’s disease (PD). Structural alterations were explored by researchers and found extensive cortical and subcortical atrophy might be related to the development of cognitive impairment in PD 1-6. However, the critical alterations of cognitive impairment, especially the differences between PD patients who convert to PD-MCI (PD converters) and those who remain cognitively stable (PD nonconverters) were unclear. Moreover, few studies have explored the association between PD related metabolic and pathological alterations and the gray matter (GM) changes.

Thus, we combined cross-sectional and longitudinal voxel-based morphometry (VBM) analyses to observe the structural topologies of PD converters and further update current knowledge regarding the roles of pathological proteins as well as dopamine in cognition related structural alterations.


This retrospective study collected fifty-one PD patients with normal cognition at baseline and 25 healthy controls (HCs) from PPMI. Those who convert to PD-MCI at follow-up (mean 12 months) were classified as PD converters (n = 18). And patients keep cognitively intact at follow-up were defined as PD nonconverters (n=33).

Clinical and neuropsychological data, MRI scans, dopamine transporter (DAT) scans and Cerebrospinal fluid (CSF) specimens (Aβ42, α-syn, and p-tau) information were included in this study. According to the DAT results, the striatal binding ratios (SBRs) in the right and left caudate nucleus and putamen were calculated separately.

We analyzed the GM volume differences in cross-sectional comparison and explored the progressive alterations within group. The relationships between GM atrophy and cognitive performance were assessed. Furthermore, DAT and CSF proteins were compared among three groups and the relationships with GM atrophy were evaluated.


Cross-sectionally, PD converters showed bilateral temporal atrophy at baseline, and progressive atrophy in these regions at follow-up (Figure 1A). Longitudinal comparison within group also showed increased left temporal atrophy in PD converters (Figure 2).

In PD patients, the temporal volume was positively correlated with visuospatial function which showed poor performance at baseline. And the temporal atrophy was correlated with the cognitive performance in multiple domains which were poor performed at follow-up.

The SBRs of the caudate and putamen were significantly associated with the temporal atrophy (Figure 1B). No correlation was found between CSF proteins and temporal atrophy.


Firstly, growing evidences showed that neuroimaging alterations in temporal lobe which caused by pathological changes of PD and Alzheimer’s disease were closely associated with cognitive decline in PD 3, 5, 7. Consistent with our findings, Mak et al. observed significant temporal cortical thinning in PD converters 1. The well-matched results of correlation analysis and cognitive performance further demonstrated the crucial role of temporal atrophy in the future cognitive decline in multiple domains.

Then, temporal cortex also receive abundant dopaminergic innervation and reduced dopamine receptor of the temporal lobe was detected in PD patients by using F18-DOPA positron emission tomography (PET) scan 8, 9. Credible evidence suggested that the denervation of temporal lobes could contribute to the posterior cortical deficits 10. And the loss of dopamine further influenced the function and structure of cortex 11-13. A recent hybrid PET/MR study revealed that the degeneration of striatal dopaminergic could contribute to the alterations of GM density through cortical-striatal circuits in PD 14. Consistently, a recent study report that DAT density was correlated with the GM volume of temporal gyrus in PD patients. Therefore, dopaminergic deficit might be a potential cause of cognition related temporal atrophy in PD.


In conclusion, our research provided a better understanding of the deterioration of cognitive impairment in PD and dopamine deficiency related structural alterations should come into our notice.


The authors thank the team at the department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. And the data used in the preparation of this article were obtained from the PPMI database (www.ppmi-info.org/data). PPMI—a public-private partnership—is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie, Allergan, Avid, Biogen, Biolegend, Bristol-Myers Squibb, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, SANOFI GENZYME, Servier, Takeda, Teva, and UCB (www.ppmi-info.org/fundingpartners).


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Cross-sectional analysis. A, Parallel comparison among three groups at baseline and follow-up (False discovery rate (FDR) corrected, p<0.05); B, The correlations between baseline right temporal volume with baseline SBRs in right and putamen right caudate (FDR corrected). FDR: False discovery rate; SBRs: Striatal binding ratios.

Longitudinal analysis. A, Longitudinal comparison of GMV within groups. (GRF corrected; Voxel P=0.005; Cluster P=0.01; two tailed); B, The rate of change in GMV in three clusters; C, The correlation between the rate of change in GMV of cluster 1 with the rate of change in LNS in PD converters. The rate of change in LNS and the rate of change in GMV were calculated as: the change rate = (Follow-up - Baseline) / Baseline. GMV: gray matter volume; GRF: Gaussian Random Field; LNS: Letter-Number Sequencing. ***: P≤0.001; **: 0.001< P < 0.01; *: 0.01 < P < 0.05

Baseline and longitudinal participants characteristics.

R: Right; L: Left; MDS-UPDRS III: part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; CSF: cerebrospinal fluid; SBRs: striatal binding ratios; MoCA: Montreal Cognitive Assessment. A = Comparison among PD converters, nonconverters and HCs; B = PD converters vs PD nonconverters; C = PD converters vs HCs; D = PD nonconverters vs HCs. a ANOVA = PD converters, PD nonconverters, HCs; b Kruskal Wallis Test = PD converters, PD nonconverters and HCs; c Wilcoxon rank-sum test = PD converters, PD nonconverters; d Independent Sample T test = PD converters, PD nonconverters

Anatomical location of significant GMV differences among three groups.

R: Right; L: Left; Sup: superior; Mid: middle; Inf: inferior.

Significant GMV differences in longitudinal comparison.

R: Right; L: Left. Sup: superior; Mid: middle; Inf: inferior.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)