Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

Sygrid van der Zee; Martijn L. T. M. Muller; Prabesh Kanel; Teus van Laar; Nicolaas I. Bohnen

doi:10.1002/mds.28360

Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

Sygrid van der Zee, Martijn L. T. M. Muller, Prabesh Kanel, Teus van Laar, Nicolaas I. Bohnen^*

^*Bijbehorende auteur voor dit werk

Movement Disorder (MD)

Onderzoeksoutput › Academic › peer review

28 Citaten (Scopus)

58 Downloads (Pure)

Samenvatting

BACKGROUND: The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes.

OBJECTIVE: The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD.

METHODS: A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18 F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age-matched, gender-matched, and educational level-matched control group. Correlations between domain-specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease-specific versus normal aging effects.

RESULTS: Voxel-based whole-brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus.

CONCLUSION: Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease-specific and aging effects. © 2020 International Parkinson and Movement Disorder Society.

Originele taal-2	English
Pagina's (van-tot)	642-650
Aantal pagina's	9
Tijdschrift	Movement Disorders
Volume	36
Nummer van het tijdschrift	3
Vroegere onlinedatum	2-nov.-2020
DOI's	https://doi.org/10.1002/mds.28360
Status	Published - mrt.-2021

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10.1002/mds.28360

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@article{8addbc3d707943bf9cc06dc6742437f5,

title = "Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease",

abstract = "BACKGROUND: The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes.OBJECTIVE: The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD.METHODS: A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18 F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age-matched, gender-matched, and educational level-matched control group. Correlations between domain-specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease-specific versus normal aging effects.RESULTS: Voxel-based whole-brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus.CONCLUSION: Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease-specific and aging effects. {\textcopyright} 2020 International Parkinson and Movement Disorder Society.",

keywords = "Aged, Cholinergic Agents, Cognition, Cognitive Dysfunction, Denervation, Humans, Middle Aged, Neuropsychological Tests, Parkinson Disease/diagnostic imaging, Positron-Emission Tomography",

author = "{van der Zee}, Sygrid and Muller, {Martijn L. T. M.} and Prabesh Kanel and {van Laar}, Teus and Bohnen, {Nicolaas I.}",

note = "Funding Information: Study funded by National Institutes of Health (P01 NS015655, RO1 NS070856, P50 NS091856), Department of Veterans Affairs grant (I01 RX001631), and the Michael J. Fox Foundation. Funding Information: Dr. Kanel and Ms. Van der Zee have nothing to disclose. Dr. Van Laar has received research support from the Weston Brain Institute, speaker fees from Brittania and is on the advisory boards of Brittania and AbbVie, and Medtronic and is on the advisory boards of LTI and Neuroderm. Dr. Muller has received research support from the National Institutes of Health, Michael J. Fox Foundation, and the Department of Veteran Affairs. Dr. Bohnen has received research funding from the National Institutes of Health, Department of Veterans Affairs, and the Michael J. Fox Foundation, Eisai, and EIP Pharma. He has participated in an Eisai advisory board and received in kind research support from Expansion Therapeutics and Innovative Health Solutions. Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",

year = "2021",

month = mar,

doi = "10.1002/mds.28360",

language = "English",

volume = "36",

pages = "642--650",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "Wiley",

number = "3",

}

TY - JOUR

T1 - Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

AU - van der Zee, Sygrid

AU - Muller, Martijn L. T. M.

AU - Kanel, Prabesh

AU - van Laar, Teus

AU - Bohnen, Nicolaas I.

N1 - Funding Information: Study funded by National Institutes of Health (P01 NS015655, RO1 NS070856, P50 NS091856), Department of Veterans Affairs grant (I01 RX001631), and the Michael J. Fox Foundation. Funding Information: Dr. Kanel and Ms. Van der Zee have nothing to disclose. Dr. Van Laar has received research support from the Weston Brain Institute, speaker fees from Brittania and is on the advisory boards of Brittania and AbbVie, and Medtronic and is on the advisory boards of LTI and Neuroderm. Dr. Muller has received research support from the National Institutes of Health, Michael J. Fox Foundation, and the Department of Veteran Affairs. Dr. Bohnen has received research funding from the National Institutes of Health, Department of Veterans Affairs, and the Michael J. Fox Foundation, Eisai, and EIP Pharma. He has participated in an Eisai advisory board and received in kind research support from Expansion Therapeutics and Innovative Health Solutions. Publisher Copyright: © 2020 International Parkinson and Movement Disorder Society

PY - 2021/3

Y1 - 2021/3

N2 - BACKGROUND: The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes.OBJECTIVE: The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD.METHODS: A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18 F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age-matched, gender-matched, and educational level-matched control group. Correlations between domain-specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease-specific versus normal aging effects.RESULTS: Voxel-based whole-brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus.CONCLUSION: Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease-specific and aging effects. © 2020 International Parkinson and Movement Disorder Society.

AB - BACKGROUND: The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes.OBJECTIVE: The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD.METHODS: A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18 F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age-matched, gender-matched, and educational level-matched control group. Correlations between domain-specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease-specific versus normal aging effects.RESULTS: Voxel-based whole-brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus.CONCLUSION: Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease-specific and aging effects. © 2020 International Parkinson and Movement Disorder Society.

KW - Aged

KW - Cholinergic Agents

KW - Cognition

KW - Cognitive Dysfunction

KW - Denervation

KW - Humans

KW - Middle Aged

KW - Neuropsychological Tests

KW - Parkinson Disease/diagnostic imaging

KW - Positron-Emission Tomography

U2 - 10.1002/mds.28360

DO - 10.1002/mds.28360

M3 - Article

C2 - 33137238

SN - 0885-3185

VL - 36

SP - 642

EP - 650

JO - Movement Disorders

JF - Movement Disorders

IS - 3

ER -