Cognitive decline profiles differ in Parkinson disease dementia and dementia with Lewy bodies

Smirnov, Denis S.; Galasko, Douglas; Edland, Steven D.; Filoteo, J. Vincent; Hansen, Lawrence A.; Salmon, David P.

doi:10.1212/wnl.0000000000009434

Cited by 52 publications

(73 citation statements)

References 49 publications

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“…Of note, DLB and PDD share many pathological and clinical features and are usually considered as two clinical entities on a spectrum of Lewy body disease 8,11 . From a neuropsychological perspective, it has been shown that PDD and DLB may have different cognitive profiles, such as the presence of a more severe impairment in executive functions for PDD and in memory for DLB, and trajectories of cognitive decline, which appear to be more rapid for DLB in the language domain 145 . However, at the earliest stages of dementia, worse performance on tests of attention and executive functions and construc tive abilities has been observed in DLB than in PDD 146 .…”

Section: Parkinson Disease Dementiamentioning

confidence: 99%

Parkinson disease-associated cognitive impairment

Aarsland

Batzu

Halliday

et al. 2021

Nat Rev Dis Primers

664

417

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Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment.

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Section: Parkinson Disease Dementiamentioning

confidence: 99%

Parkinson disease-associated cognitive impairment

Aarsland

Batzu

Halliday

et al. 2021

Nat Rev Dis Primers

664

417

View full text Add to dashboard Cite

show abstract

“…Conversely, treatments targeting tau (or perhaps ADNC more broadly) may affect memory and global cognition to a greater degree than executive/visuospatial measures. While recent work suggests that memory and language are most sensitive outcome measures of cognitive change in dementia with Lewy bodies relative to visuospatial and executive function in Parkinson’s disease dementia [ 55 ], the study did not aim to differentiate the impact of each pathology on cognition, but rather the nature of cognitive changes associated with each clinical diagnosis. Notably, dementia with Lewy bodies typically exhibit concomitant ADNC pathology, which may have driven the decline in memory and language in this particular study [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…While recent work suggests that memory and language are most sensitive outcome measures of cognitive change in dementia with Lewy bodies relative to visuospatial and executive function in Parkinson’s disease dementia [ 55 ], the study did not aim to differentiate the impact of each pathology on cognition, but rather the nature of cognitive changes associated with each clinical diagnosis. Notably, dementia with Lewy bodies typically exhibit concomitant ADNC pathology, which may have driven the decline in memory and language in this particular study [ 55 ]. As disease modifying therapies for specific neuropathology emerge, it will be increasingly important to utilize outcome measures directly impacted by that specific pathology rather than co-occurring pathologies, which is often the case in dementia with Lewy bodies.…”

Section: Discussionmentioning

confidence: 99%

Cognition at Each Stage of Lewy Body Disease with Co-occurring Alzheimer’s Disease Pathology1

Ryman

Yutsis

Tian

et al. 2021

JAD

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Background: Alzheimer’s disease neuropathologic change (ADNC) may contribute to dementia in patients with Lewy body disease (LBD) pathology. Objective: To examine how co-occurring ADNC impacts domain specific cognitive impairments at each pathologic stage (brainstem, limbic, cerebral cortical) of LBD. Methods: 2,433 participants with antemortem longitudinal neuropsychological assessment and postmortem neuropathological assessment from the National Alzheimer’s Coordinating Center’s Uniform Data Set were characterized based on the evaluation of ADNC and LBD. Longitudinal mixed-models were used to derive measures of cumulative cognitive deficit for each cognitive domain at each pathologic stage of LBD (brainstem, limbic, and cerebral cortical). Results: 111 participants with a pathologic diagnosis of LBD, 741 participants with combined LBD and ADNC, 1,357 participants with ADNC only, and 224 with no pathology (healthy controls) were included in the analyses. In the executive/visuospatial domain, combined LBD and ADNC showed worse deficits than LBD only when Lewy bodies were confined to the brainstem, but no difference when Lewy bodies extended to the limbic or cerebral cortical regions. The cerebral cortical LBD only group exhibited greater executive/visuospatial deficits than the ADNC only group. By contrast, the ADNC only group and the combined pathology group both demonstrated significantly greater cumulative memory deficits relative to Lewy body disease only, regardless of stage. Conclusion: The impact of co-occurring ADNC on antemortem cumulative cognitive deficits varies not only by domain but also on the pathological stage of Lewy bodies. Our findings stress the cognitive impact of different patterns of neuropathological progression in Lewy body diseases.

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“…There was no significant difference in the speed of cognitive deterioration between patients with pure AD and AD with co-pathology, but the presence of AD pathology in those that had LBD led to faster cognitive impairment [ 29 ]. Others reported that some patients initially diagnosed with DLB had enough AD pathology to be classified as AD as well, historically known as the Lewy body variant of AD [ 34 ].…”

Section: Dysautonomia As a Results Of Brain Co-pathologiesmentioning

confidence: 99%

Dysautonomia in Alzheimer's Disease

et al. 2020

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Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature focusing on Alzheimer's disease cardinal cognitive features, autonomic nervous system dysfunction remains understudied despite being common in the elderly. In this article, we reviewed the evidence for autonomic nervous system involvement in Alzheimer's disease. We identified four major potential causes for dysautonomia in Alzheimer's disease, out of which two are well-studied (comorbidities and medication) and two are rather hypothetical (Alzheimer's pathology and brain co-pathology). Although there appears to be some evidence linking Alzheimer's disease pathology to autonomic nervous system dysfunction, there is an important gap between two types of studies; histopathologic studies do not address dysautonomia manifestations, whereas clinical studies do not employ histopathologic diagnostic confirmation. Moreover, brain co-pathology is emerging as an important confounding factor. Therefore, we consider the correlation between dysautonomia and Alzheimer's disease to be an open question that needs further study. Nevertheless, given its impact on morbidity and mortality, we emphasize the importance of assessing autonomic dysfunction in patients with Alzheimer clinical syndrome.

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Cognitive decline profiles differ in Parkinson disease dementia and dementia with Lewy bodies

Cited by 52 publications

References 49 publications

Parkinson disease-associated cognitive impairment

Parkinson disease-associated cognitive impairment

Cognition at Each Stage of Lewy Body Disease with Co-occurring Alzheimer’s Disease Pathology1

Dysautonomia in Alzheimer's Disease

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