Structural and metabolic correlates of neuropsychological profiles in multiple system atrophy and Parkinson's disease

Kübler, Dorothee; Kobylecki, Christopher; McDonald, Kathryn; Anton‐Rodriguez, José; Herholz, Karl; Carter, Stephen F.; Hinz, Rainer; Thompson, Jennifer C.; Al‐Fatly, Bassam; Gerhard, Alexander

doi:10.1016/j.parkreldis.2022.105277

Cited by 6 publications

(3 citation statements)

References 36 publications

(46 reference statements)

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“…Tract-based FA values decreased in the bilateral corticospinal tract, anterior and posterior cingulum, fornix, bilateral superior thalamic radiation, corpus callosum, bilateral superior and inferior longitudinal fasciculus, superior and inferior fronto-occipital fascicles, and bilateral parieto-occipital tract [ 181 ]. Widespread frontostriatal WM tract FA reduction was seen in PD-CI [ 184 ]. WM abnormalities, associated with significantly lower neurite density and orientation dispersion in the prefrontal region, the cingulum bundle and in thalamo-frontal tracts, were related to cognitive decline [ 58 , 182 ].…”

Section: Neuroimaging Findings In CI In Pd (See Supplement ...mentioning

confidence: 99%

“…The following supporting information can be downloaded at . References [ 42 , 55 , 80 , 140 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 2...…”

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Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.

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Section: Neuroimaging Findings In CI In Pd (See Supplement ...mentioning

confidence: 99%

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Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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“…Multiple System Atrophy (MSA) is a neurodegenerative disorder characterized by marked motor impairment, parkinsonian features, cerebellar ataxia, tremor, cortico-spinal tract dysfunction, autonomic abnormalities, and deficits in executing functions (Krismer and Wenning 2017 ; Jellinger 2020 ; Kübler et al 2023 ). It chiefly comprises of two major variants depending on the dominant clinical phenotype, one of which is MSA-P.…”

Section: Introductionmentioning

confidence: 99%

The ‘α-synucleinopathy syndicate’: multiple system atrophy and Parkinson’s disease

Sian-Hülsmann

Riederer

2023

J Neural Transm

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Multiple System Atrophy (MSA) and Parkinson’s diseases (PD) are elite members of the α-synucleinopathy organization. Aberrant accumulations of the protein α-synuclein characterize them. A plethora of evidence indicates the involvement of these rogue inclusions in a cascade of events that disturb cellular homeostasis resulting in neuronal dysfunction. These two neurodegenerative diseases share many features both clinically and pathologically. Cytotoxic processes commonly induced by reactive free radical species have been associated with oxidative stress and neuroinflammation, frequently reported in both diseases. However, it appears they have characteristic and distinct α-synuclein inclusions. It is glial cytoplasmic inclusions in the case of MSA while Lewy bodies manifest in PD. This is probably related to the etiology of the illness. At present, precise mechanism(s) underlying the characteristic configuration of neurodegeneration are unclear. Furthermore, the “prion-like” transmission from cell to cell prompts the suggestion that perhaps these α-synucleinopathies are prion-like diseases. The possibility of some underlying genetic foul play remains controversial. But as major culprits of pathological processes or even single triggers of PD and MSA are the same—like oxidative stress, iron-induced pathology, mitochondriopathy, loss of respiratory activity, loss of proteasomal function, microglial activation, neuroinflammation—it is not farfetched to assume that in sporadic PD and also in MSA a variety of combinations of susceptibility genes contribute to the regional specificity of pathological onset. These players of pathology, as mentioned above, in a synergistic combination, are responsible for driving the progression of PD, MSA and other neurodegenerative disorders. Elucidating the triggers and progression factors is vital for advocating disease modification or halting its progression in both, MSA and PD.

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Mild cognitive impairment in multiple system atrophy: a brain network disorder

Ka¹

2023

J Neural Transm

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Structural and metabolic correlates of neuropsychological profiles in multiple system atrophy and Parkinson's disease

Cited by 6 publications

References 36 publications

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

The ‘α-synucleinopathy syndicate’: multiple system atrophy and Parkinson’s disease

Mild cognitive impairment in multiple system atrophy: a brain network disorder

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