Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer’s disease dementia

Grothe, Michel J.; Schuster, Christina; Bauer, Florian; Heinsen, Helmut; Prudlo, Johannes; Teipel, Stefan J.

doi:10.1007/s00415-014-7439-z

Cited by 122 publications

(92 citation statements)

References 72 publications

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“…In the present study, SI volume was reduced in dementia groups compared with healthy controls, which was consistent with previous studies (Grothe et al ., 2014; Hanyu et al ., 2005; Whitwell et al ., 2007). In addition, atrophic changes within the SI appeared to be associated with dementia severity and cognitive fluctuations in DLB.…”

Section: Discussionmentioning

confidence: 99%

Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL‐VBM study

Colloby

Elder

Rabee

et al. 2016

Int J Geriat Psychiatry

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ObjectivesSeveral cholinergic nuclei, and in particular the nucleus basalis of Meynert, are localised to the substantia innominata in the basal forebrain. These nuclei provide major cholinergic innervation to the cerebral cortex and hippocampus, and have an essential role in cognitive function. The aim of this study was to investigate volumetric grey matter (GM) changes in the substantia innominata from structural T1 images in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy older participants using voxel‐based morphometry.MethodsParticipants (41 DLB, 47 AD and 39 controls) underwent 3 T T1 magnetic resonance imaging and cognitive assessments. Voxel‐based morphometry analysis used SPM8 with a substantia innominata brain mask to define the subspace for voxel GM analyses. Group differences, and selected behavioural and clinical correlates, were assessed.ResultsCompared with that in controls, bilateral GM loss in the substantia innominata was apparent in both AD and DLB. Relative to controls, significant bilateral GM loss in the substantia innominata was observed in DLB and AD. In DLB, significant associations were also observed between substantia innominata GM volume loss, and the levels of cognitive impairment and severity of cognitive fluctuations.ConclusionsRelative to that controls, atrophy of the substantia innominata was apparent in DLB and AD, and is associated with specific clinical manifestations in DLB. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

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Section: Discussionmentioning

confidence: 99%

Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL‐VBM study

Colloby

Elder

Rabee

et al. 2016

Int J Geriat Psychiatry

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“…Similarly, cholinergic neural deficits and functional impairment have long been recognized as symptomatic features of PD and NCDLB [22][23][24][25][26][27][28]. 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].…”

Section: Cholinergic Lewy Pathology In the Ensmentioning

confidence: 99%

“…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].…”

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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“…In DLB, degeneration of cholinergic neurons of the basal ganglia projecting to the cortex has been identified in disease pathology [13]. The Neuropsychiatric symptoms observed by the patients and their caregivers have also been attributed to this cholinergic deficit.…”

Section: Introductionmentioning

confidence: 98%