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Recent Advances in Cholinergic Imaging and Cognitive Decline—Revisiting the Cholinergic Hypothesis of Dementia

  • Neurology of Aging (K. Marder, Section Editor)
  • Published:
Current Geriatrics Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Although the cholinergic hypothesis of dementia provided a successful paradigm for the development of new drugs for dementia, this hypothesis has waned in popularity. Cholinergic brain imaging may provide novel insights into the viability of this hypothesis.

Recent Findings

Cholinergic receptor and forebrain volumetric studies suggest an important role of the cholinergic system in maintaining brain network integrity that may deteriorate with cognitive decline in Alzheimer disease (AD) and Lewy body disorders (LBD). Bidirectional changes in regional receptor expression may suggest the presence of compensatory responses to neurodegenerative injury. Cholinergic system changes are more complex in LBD because of additional subcortical degenerations compared to AD. Cholinergic-dopaminergic interactions affect attentional, verbal learning, and executive functions, and impairments in these two transmitter systems may jointly increase the risk of dementia in Parkinson’s disease.

Summary

The cholinergic hypothesis is evolving from a primary focus on memory toward expanded cognitive functions modulated by regionally more complex and interactive brain networks. Cholinergic network adaptation may serve as a novel research target in neurodegeneration.

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Abbreviations

AChE:

Acetylcholinesterase

AD:

Alzheimer disease

CBFB:

cholinergic basal forebrain

DLB:

dementia with Lewy bodies

DMN:

default mode network

MCI:

mild cognitive impairment

MRI:

magnetic resonance imaging

NBM:

nucleus basalis of Meynert

PD:

Parkinson’s disease

PDD:

Parkinson’s disease with dementia

PPN:

pedunculopontine nucleus

PET:

Positron emission tomography

SPECT:

Single-photon computed emission tomography

VAChT:

Vesicular acetylcholine transporter

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Acknowledgements

The presented research data from the authors’ work was supported by grants from the NIH [P01 NS015655, RO1 NS070856, with additional support from P50 NS091856], Department of Veterans Affairs [I01 RX000317], and the Michael J. Fox Foundation.

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Authors and Affiliations

  1. Department of Radiology, University of Michigan, Ann Arbor, MI, USA

    Nicolaas I. Bohnen & Martijn L. T. M. Müller

  2. Department of Neurology, University of Michigan, Ann Arbor, MI, USA

    Nicolaas I. Bohnen

  3. Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, USA

    Nicolaas I. Bohnen

  4. Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, MI, USA

    Nicolaas I. Bohnen & Martijn L. T. M. Müller

  5. Functional Neuroimaging, Cognitive and Mobility Laboratory, University of Michigan, Domino’s Farms, Lobby B, Suite 1000, Level I; 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI, 48105-9755, USA

    Nicolaas I. Bohnen

  6. German Center for Neurodegenerative Diseases (DZNE) - Rostock/Greifswald, Rostock, Germany

    Michel J. Grothe & Stefan J. Teipel

  7. Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany

    Michel J. Grothe & Stefan J. Teipel

  8. Department of Psychology, Manchester Metropolitan University, Manchester, UK

    Nicola J. Ray

Authors
  1. Nicolaas I. Bohnen
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  2. Michel J. Grothe
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  3. Nicola J. Ray
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  4. Martijn L. T. M. Müller
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  5. Stefan J. Teipel
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Corresponding author

Correspondence to Nicolaas I. Bohnen.

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Conflict of Interest

Michael Grothe and Nicola Ray declare no conflict of interest.

Nicolaas Bohnen reports grants from NIH, the Department of Veterans Affairs, the Michael J. Fox foundation, Axovant Sciences, and Chase Pharmaceuticals, outside the submitted work.

Stefan Teipel reports being an advisory board member of MSD Sharp and Dohme GMBH.

Martijn Müller reports grants from the NIH, the Michael J. Fox Foundation, and Veterans Affairs, during the conduct of this study.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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This article is part of the Topical Collection on Neurology of Aging

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Bohnen, N.I., Grothe, M.J., Ray, N.J. et al. Recent Advances in Cholinergic Imaging and Cognitive Decline—Revisiting the Cholinergic Hypothesis of Dementia. Curr Geri Rep 7, 1–11 (2018). https://doi.org/10.1007/s13670-018-0234-4

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