Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra

Rinne, Juha O.; Rummukainen, Jaana; Paljärvi, Leo; Rinne, U. K.

doi:10.1002/ana.410260107

Cited by 303 publications

(135 citation statements)

References 29 publications

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“…Rinne, Rummukainen, Paljarui, and Rinne (1989) reported a significant correlation between dementia severity in PD and neuronal loss in select regions of the substantia nigra that have specific projections to the caudate nucleus, suggesting that this particular subcortical region may be critical in the cognitive profile exhibited by PD patients. Dopamine depletion in the caudate nucleus (as measured by positron emission tomography [PET]) has been associated with cognitive executive declines in early-stage patients with PD (Carbon et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson's Disease

Zgaljardic

Borod

Foldi

et al. 2006

Journal of Clinical and Experimental Neuropsychology

167

122

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Parkinson's disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson's disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.

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Section: Discussionmentioning

confidence: 99%

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson's Disease

Zgaljardic

Borod

Foldi

et al. 2006

Journal of Clinical and Experimental Neuropsychology

167

122

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“…In contrast, the dorsal and medial neuronal cell groups are less vulnerable. Loss of medial neuronal cell groups (e.g., ventral tegmental region or A10) may be increased in parkinsonian disorders with dementia (Rinne et al 1989). …”

Section: Distribution Of Pathologymentioning

confidence: 99%

Parkinson's Disease and Parkinsonism: Neuropathology

Dickson¹

2012

Cold Spring Harbor Perspectives in Medicine

679

526

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Parkinsonism, the clinical term for a disorder with prominent bradykinesia and variable associated extrapyramidal signs and symptoms, is accompanied by degeneration of the nigrostriatal dopaminergic system, with neuronal loss and reactive gliosis in the substantia nigra found at autopsy. Parkinsonism is pathologically heterogeneous, with the most common pathologic substrates related to abnormalities in the presynaptic protein a-synuclein or the microtubule binding protein tau. In idiopathic Parkinson's disease (PD), a-synuclein accumulates in neuronal perikarya (Lewy bodies) and neuronal processes (Lewy neurites). The disease process is multifocal and involves select central nervous system neurons and peripheral autonomic nervous system neurons. The particular set of neurons affected determines nonmotor clinical presentations. Multiple system atrophy (MSA) is the other major a-synucleinopathy. It is also associated with autonomic dysfunction and in some cases with cerebellar signs. The hallmark histopathologic feature of MSA is accumulation of a-synuclein within glial cytoplasmic inclusions (GCI). The most common of the Parkinsonian tauopathies is progressive supranuclear palsy (PSP), which is clinically associated with severe postural instability leading to early falls. The tau pathology of PSP also affects both neurons and glia. Given the population frequency of PD, a-synuclein pathology similar to that in PD, but not accompanied by neuronal loss, is relatively common (10% of people over 65 years of age) in neurologically normal individuals, leading to proposed staging schemes for PD progression. Although MSA-like and PSP-like pathology can be detected in neurologically normal individuals, such cases are too infrequent to permit assessment of patterns of disease progression.

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“…DISCUSSION Diffuse cortical Lewy bodies and a-synuclein, 10 loss of basal forebrain cholinergic neurons 8 and medial nigral dopaminergic neurons, 9 and Alzheimer disease (AD) pathology 11 have all been implicated in the development of cognitive impairments and dementia in PD. The results of this study support the contribution of cortical amyloid Ab deposits.…”

Section: Pib Pet and Image Analyses N-methyl-[mentioning

confidence: 99%

“…4,5 Dementia is common in PD, with a relative risk two-to sixfold higher than the general population, 6 corresponding to lifetime risk estimates of 30%-80%. 7 Multiple pathologic processes have been linked to dementia in PD: degeneration of basal forebrain cholinergic nuclei, 8 frontalsubcortical circuit deafferentation due to degeneration of brainstem dopaminergic neurons, 9 diffuse cortical Lewy bodies associated with a-synuclein, 10 and Alzheimer-like lesions with Ab-laden senile plaques. 11 Techniques to determine which of these is dominant have been limited until now.…”

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confidence: 99%

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia

et al. 2013

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Objective: To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia.Methods: In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition and 11 met criteria for PD-MCI at study baseline. All subjects underwent standardized neurologic and neuropsychological examinations and PiB PET at baseline, and clinical examinations were conducted annually for up to 5 years.Results: At baseline, precuneus PiB retention did not distinguish PD-MCI from PD-nl. Subjects with PD-MCI declined more rapidly than PD-nl subjects on cognitive tests of memory, executive function, and activation retrieval. Of the 35 PD-nl subjects, 8 progressed to PD-MCI and 1 to dementia; of the 11 PD-MCI subjects, 5 converted to dementia. Both higher PiB retention and a diagnosis of PD-MCI predicted a greater hazard of conversion to a more severe diagnosis. Baseline PiB retention predicted worsening in executive function over time. The APOE e4 allele also related to worsening in executive function, as well as visuospatial function, activation retrieval, and performance on the Mini-Mental State Examination. In contrast to its relation to cognitive decline, PiB retention did not affect progression of motor impairment.Conclusions: At baseline measurements, amyloid burden does not distinguish between cognitively impaired and unimpaired subjects with PD without dementia, but our data suggest that amyloid contributes to cognitive, but not motor, decline over time.

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Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra

Cited by 303 publications

References 29 publications

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson's Disease

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson's Disease

Parkinson's Disease and Parkinsonism: Neuropathology

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia

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