Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Scharre, Douglas W.; Chang, Shu Ing; Nagaraja, Haikady N.; Park, Ariane; Adeli, Anahita; Agrawal, Punit; Kloos, Anne; Kegelmeyer, Deb; Linder, Shannon; Fritz, Nora; Kostyk, Sandra K.; Kataki, Maria

doi:10.3233/jad-160384

Cited by 27 publications

(23 citation statements)

References 55 publications

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“…Pathological verification would have provided important evidence of the diagnostic accuracy but is difficult to perform in a large multicenter study. A larger proportion with dopamine transporter imaging, and more detailed tests of motor, cognitive and behavioral changes would have potentially improved diagnostic accuracy [24]. The variability in rates of decline complicates the interpretation of the findings.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Kramberger

Auestad

García-Ptacek

et al. 2017

JAD

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Background & Objective The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD) patients. Methods Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1290 patients (835 DLB, 198 PDD and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates to model MMSE decline over time. Several subgroup analyses were performed, defined were run by anti-dementia medication use, baseline MMSE score, and DLB core features. Results The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p=0.07 compared to DLB) and 1.8 in PDD (p=0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. Conclusions The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

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Section: Discussionmentioning

confidence: 99%

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Kramberger

Auestad

García-Ptacek

et al. 2017

JAD

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“…Increasingly, cholinergic impairments in PD and NCDLB are attributed to Lewy Body pathology (Cholinergic impairment does not appear to be a consistent finding in Alzheimer's disease (AD) [27,42]. Research consistently demonstrates that autonomic dysfunction is a feature of PD and NCDLB, but not AD and that α-synuclein expression is increased in NCDLB and PD, but not in AD [2,7,9,[43][44][45][46]. For this reason, AD is not included in this discussion) [23,28,29].…”

Section: Cholinergic Lewy Pathology In the Ensmentioning

confidence: 99%

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

Lepkowsky¹

2017

IJGS

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Abstractα-synuclein (Lewy Body) pathology is commonly found in the enteric nervous system (ENS) of patients diagnosed with Neurocognitive Disorder with Lewy Bodies (NCDLB) and Parkinson's Disease (PD). Lewy pathology in the ENS can produce symptoms of bowel immotility, including constipation, obstipation, and bowel impaction. These symptoms significantly reduce the quality of life for the patient, producing hardship for the patient and care providers. In Lewy body patients, medical intervention using acetylcholinesterase inhibitors (AChEIs) can significantly reduce or alleviate bowel immotility. The specific mechanism through which the cholinergic agonist Donepezil mitigates Lewy Body bowel immotility is explained. Practice, 1143 Deer Trail Lane, Solvang, California 93463, USA, Tel: 805-688-1229 Fax: 805-686-9382; E-mail: clepkowsky@gmail.com of α-synuclein aggregates in the MP predates cognitive and motor functional manifestations of Lewy body diseases so consistently that it has been nominated as a potential biomarker for Lewy pathology [10,17,30]. Symptomatic Manifestations of Cholinergic Lewy Pathology in the ENSLewy body cholinergic impairment in the ENS manifests symptomatically as gastric immotility and constipation [13,[31][32][33][34][35][36][37][38][39][40][41]. Increased colonic transit time and impaired gastric emptying are frequently found in PD patients [35,42]. The prevalence of constipation in PD is at least three times that of the general population, leading some researchersto suggest that constipation might be a universal feature of PD [47,48]. Bowel immotility can occur 20 years before diagnosis of PD or NCDLB, suggesting that it might be a prodromal symptom for both disorders [5,19,36,44,[49][50][51][52].As α-synuclein pathology advances in the ENS, symptoms of gastric immotility advance from constipation to obstipation and impaction. Escalating gastric immotility in PD and NCDLB can interfere with mobility, sleep, cognition, and mood, increasing the cost of care, and potentially debilitating and/or dramatically reducing the quality of life for patients. [4,34,36,[53][54][55][56] Potential Exacerbation of ENS Symptoms by AntiParkinson MedicationLPD and NCDLB patients with significant Parkinsonian motoric/gait features are often prescribed L-dopa agents like Carbidopa-Levodopa (known also by the brand names Sinemet and Stalevo) in order to preserve gait, balance, and other basic motor functions [40,57,58]. Carbidopa-Levodopa's potential side effects include constipation [59]. which can complicate or exacerbate gastric immotility due to ENS Lewy pathology. Medications frequently used for the treatment of resting tremor in PD and NCDLB includeTrihexyphenidyl (marketed as Artane or Trihex) and Benztropinemesylate (marketed as Cogentin), identified as definite anticholinergics that can also exacerbate gastric immotility through suppression of the cholinergic neurotransmitter pathways innervating the ENS [58,[60][61][62].

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“…(Scharre et al, 2016). The etiology of PD is unknown in about 75% of cases; however, evidence shows that PD is a consequence of both environmental factors and genetic susceptibility (Biernacka et al, 2016;Marques et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

“…However, alphasynuclein protein aggregation and its toxicity seems to be a consequence of natural aging changes in cells, such as increased ROS, and a predisposition toward developing PD (Scharre et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…hiPSC-derived neurons are not subject to all changes involved in aging. Specifically, increased ROS is characteristic of both aged neurons and neurons from patients with PD (Scharre et al, 2016;Ross et al, 2015). Therefore, an addition stressor is required to mimic the alterations that occur during normal aging, including dopaminergic sensitivity.…”

Section: G D H a E B Fmentioning

confidence: 99%

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Estudo dos efeitos da superexpressão da alfa-sinucleína sobre o tráfego mitocondrial e autofagia em leveduras, células SH-SY5Y e neurônios dopaminérgicos derivados de hiPSC de pacientes com doença de Parkinson

Melo¹

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Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Cited by 27 publications

References 55 publications

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

Estudo dos efeitos da superexpressão da alfa-sinucleína sobre o tráfego mitocondrial e autofagia em leveduras, células SH-SY5Y e neurônios dopaminérgicos derivados de hiPSC de pacientes com doença de Parkinson

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