Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson’s disease

Zarkali, Angeliki; McColgan, Peter; Leyland, Louise‐Ann; Lees, Andrew J.; Weil, Rimona S

doi:10.1101/2020.10.12.335547

Cited by 5 publications

(5 citation statements)

References 51 publications

(64 reference statements)

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“…Thalamic regions were amongst the highest contributors to this transition. Thalamic involvement has been previously described in visual hallucinations(56,71) and we recently showed longitudinal changes in grey and white matter within the medial mediodorsal thalamus(72). This provides further evidence of the thalamus as a key driver of network imbalance in PD-hallucinations(65,73).…”

Section: Discussionmentioning

confidence: 64%

Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson’s disease

Zarkali

Luppi

Stamatakis

et al. 2021

Preprint

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Background: Visual hallucinations in Parkinsons disease (PD) are transient, suggesting a change in dynamic brain states. However, the causes underlying these dynamic brain changes are not known. Methods: Focusing on fundamental network properties of integration and segregation, we used rsfMRI to examine alterations in temporal dynamics in PD patients with hallucinations (n=16) compared to those without hallucinations (n=75) and a group of normal controls (n=32). We used network control theory to examine how structural connectivity guides transitions between functional states. We then studied the brain regions most involved in these state transitions, and examined corresponding neurotransmitter density profiles and receptor gene expression in health. Results: There were significantly altered temporal dynamics in PD with hallucinations, with an increased proportion of time spent in the Segregated state compared to non-hallucinators and controls; less between-state transitions; and increased dwell time in the Segregated state. The energy cost needed to transition from integrated-to-segregated state was lower in PD-hallucinators compared to non-hallucinators. This was primarily driven by subcortical and transmodal cortical brain regions, including the thalamus and default mode network regions. The regional energy needed to transition from integrated-to-segregated state was significantly correlated with regional neurotransmitter density and gene expression profiles for serotoninergic (including 5HT2A), GABAergic, noradrenergic and cholinergic but not dopaminergic density profiles. Conclusions: We describe the patterns of temporal functional dynamics in PD-hallucinations, and link these with neurotransmitter systems involved in early sensory and complex visual processing. Our findings provide mechanistic insights into visual hallucinations in PD and highlighting potential therapeutic targets.

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Section: Discussionmentioning

confidence: 64%

Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson’s disease

Zarkali

Luppi

Stamatakis

et al. 2021

Preprint

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“…It was reported that VI could predict CFI in patients with Parkinson's disease. [44][45][46] Gbessemehlan A 47 et al suggested that improving vision might be an easy way to decrease the incidence of cognitive disorders. Several ophthalmology studies reported similar results.…”

Section: Discussionmentioning

confidence: 99%

“…In terms of structure and morphology, the microstructure and morphology of white matter as well as the macroscopic structure of patients with poor vision were more extensively changed than those with normal vision. 45 One hypothesis is that VI reduces the ability of the elderly to engage in activities that maintain health and leads to reduced brain stimulation, which may be a risk factor for cognitive decline. 49,50 Another hypothesis goes that both VA and cognitive decline may share the common cause, such as age, inflammation or deterioration of central nervous function.…”

Section: Discussionmentioning

confidence: 99%

Visual impairment as a risk factor of cognitive function impairment A six-year cohort study

Cao

Hao

Wang

2023

European Journal of Ophthalmology

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Purpose To explore whether baseline visual impairment (VI) increases the risk of cognitive function impairment (CFI). Methods We conducted a population-based cohort study, with a six-year follow-up period. The exposure factor of interest in this study was VI. The Mini-Mental State Examination (MMSE) was used to assess participants’ cognitive function. The Logistic regression model was used to investigate whether baseline VI had an effect on CFI. Confounding factors were adjusted in the regression model. The odds ratio (OR) and 95% confidence interval (CI) were used to quantify the effect of VI on CFI. Results A total of 3297 participants were included in the present study. The mean age of included participants was 58.5 ± 7.2 years. Male accounted for 1480 (44.9%) of all participants. At baseline, 127 (3.9%) of the participants had VI. The MMSE score of participants who had VI at baseline decreased by 1.7 ± 3.3 points on average during the six-year follow-up, and that of participants who had no VI at baseline decreased by 1.1 ± 3.3 points on average. The difference was significant (t = 2.03, p = 0.040). Results of the multivariable Logistic regression model showed that VI was a risk factor for CFI, with an OR of 1.052 (95%CI: 1.014 to 1.092, p = 0.017). Conclusions Averagely, participants with VI experienced a decline in cognitive function 0.1 points faster per year than participants without VI, as measured by MMSE score. VI is an independent risk factor for CFI.

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“…49 We found that depression was also associated with visuoperceptual deficits which have also been shown to be associated with widespread macrostructural white matter degeneration. 39 It is most likely that PD depression is linked with these other non-motor PD features due to a shared aetiology of accelerated and more widespread Lewy body deposition in brain regions beyond the midbrain dopaminergic neurons.…”

Section: Discussionmentioning

confidence: 99%

“…38 We used this metric as our previous work in PD has shown FC to be a more sensitive measure of degeneration, compared to other fixel-based measures such as fibre density and combined fibre density and cross section. 39 FC was estimated for each fixel by calculating the distortion in fibre bundle cross-section required to warp the subject image to the template image.…”

Section: Fibre Cross-sectionmentioning

confidence: 99%

Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression

Bhome

Zarkali

Cole

et al. 2021

Preprint

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Objective Depression is a common non-motor feature of Parkinson's disease (PD) which confers significant morbidity and is often challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not yet been identified and may even represent potential therapeutic targets. Methods We performed structural and diffusion weighted imaging on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). We used fixel based analysis of diffusion weighted imaging data to calculate mean fibre cross section (FC) for white matter tracts connected to each subnucleus and assessed volume and FC at baseline and 14-20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each of the 50 thalamic subnuclei, adjusting for age, gender, intracranial volume and time. Results We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with decreases in white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. Conclusion We demonstrate that depression is associated with right thalamic PuA subnucleus volume loss and widespread thalamic white matter macrostructural changes, but that antidepressants may protect against volume loss in PD depression. Our work provides mechanistic insights for depression in PD, suggests possible benefits of actively treating depression, and a potential target for therapeutic intervention to the PuA subnucleus for PD depression.

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Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson’s disease

Cited by 5 publications

References 51 publications

Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson’s disease

Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson’s disease

Visual impairment as a risk factor of cognitive function impairment A six-year cohort study

Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression

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