Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease

Pietro Tiraboschi, Larry A. Hansen, Michael Alford, Annette Merdes, Eliezer Masliah, Leon J. Thal, Jody Corey-Bloom

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Background: Reductions in cholinergic function occur in Alzheimer disease (AD) and dementia with Lewy bodies and correlate with cognitive decline. However, whether such alterations appear in early-stage disease is unclear. Objective: To examine the timing of cholinergic deficits in AD and dementia with Lewy bodies. Methods: Autopsy series of 89 patients with AD and 50 patients with the Lewy body variant of AD (LBV). Stage of disease was stratified according to results of the last Mini-Mental State Examination (MMSE) before death as mild, moderate, severe, or very severe. We analyzed choline acetyltransferase (ChAT) activity in the midfrontal, superior temporal, and inferior parietal cortices. Results: Although compared with a normal control group ChAT activity was decreased in the AD and LBV cohorts, ChAT activity reduction for the LBV cohort was much greater. Moreover, although the decline in ChAT activity in the AD cohort compared with the normal control group was significant only for patients in later stages of the illness, the decline in the LBV cohort was significant for those who died with mild-stage disease. When less impaired patients in each cohort (MMSE, ≥ 10) underwent separate analysis, the relationship of ChAT activity with the MMSE score was strong and significant for the LBV cohort alone. Conclusions: Although cholinergic deficits are seen in both AD and LBV, loss of ChAT activity is less severe and occurs later in the clinical course of AD. Conversely, in LBV, loss of ChAT activity is already prominent in the earliest stages of the illness, suggesting that cholinergic replacement therapy may be more effective in LBV than in AD, especially in mild-stage disease.

Original languageEnglish
Pages (from-to)946-951
Number of pages6
JournalArchives of General Psychiatry
Volume59
Issue number10
Publication statusPublished - Oct 1 2002

Fingerprint

Lewy Body Disease
Lewy Bodies
Choline O-Acetyltransferase
Cholinergic Agents
Dementia
Alzheimer Disease
Control Groups
Parietal Lobe
Alzheimer's Disease
Autopsy
Cohort

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Tiraboschi, P., Hansen, L. A., Alford, M., Merdes, A., Masliah, E., Thal, L. J., & Corey-Bloom, J. (2002). Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease. Archives of General Psychiatry, 59(10), 946-951.

Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease. / Tiraboschi, Pietro; Hansen, Larry A.; Alford, Michael; Merdes, Annette; Masliah, Eliezer; Thal, Leon J.; Corey-Bloom, Jody.

In: Archives of General Psychiatry, Vol. 59, No. 10, 01.10.2002, p. 946-951.

Research output: Contribution to journalArticle

Tiraboschi, P, Hansen, LA, Alford, M, Merdes, A, Masliah, E, Thal, LJ & Corey-Bloom, J 2002, 'Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease', Archives of General Psychiatry, vol. 59, no. 10, pp. 946-951.
Tiraboschi, Pietro ; Hansen, Larry A. ; Alford, Michael ; Merdes, Annette ; Masliah, Eliezer ; Thal, Leon J. ; Corey-Bloom, Jody. / Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease. In: Archives of General Psychiatry. 2002 ; Vol. 59, No. 10. pp. 946-951.
@article{68128c91b0344317a7643a10300c2734,
title = "Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease",
abstract = "Background: Reductions in cholinergic function occur in Alzheimer disease (AD) and dementia with Lewy bodies and correlate with cognitive decline. However, whether such alterations appear in early-stage disease is unclear. Objective: To examine the timing of cholinergic deficits in AD and dementia with Lewy bodies. Methods: Autopsy series of 89 patients with AD and 50 patients with the Lewy body variant of AD (LBV). Stage of disease was stratified according to results of the last Mini-Mental State Examination (MMSE) before death as mild, moderate, severe, or very severe. We analyzed choline acetyltransferase (ChAT) activity in the midfrontal, superior temporal, and inferior parietal cortices. Results: Although compared with a normal control group ChAT activity was decreased in the AD and LBV cohorts, ChAT activity reduction for the LBV cohort was much greater. Moreover, although the decline in ChAT activity in the AD cohort compared with the normal control group was significant only for patients in later stages of the illness, the decline in the LBV cohort was significant for those who died with mild-stage disease. When less impaired patients in each cohort (MMSE, ≥ 10) underwent separate analysis, the relationship of ChAT activity with the MMSE score was strong and significant for the LBV cohort alone. Conclusions: Although cholinergic deficits are seen in both AD and LBV, loss of ChAT activity is less severe and occurs later in the clinical course of AD. Conversely, in LBV, loss of ChAT activity is already prominent in the earliest stages of the illness, suggesting that cholinergic replacement therapy may be more effective in LBV than in AD, especially in mild-stage disease.",
author = "Pietro Tiraboschi and Hansen, {Larry A.} and Michael Alford and Annette Merdes and Eliezer Masliah and Thal, {Leon J.} and Jody Corey-Bloom",
year = "2002",
month = "10",
day = "1",
language = "English",
volume = "59",
pages = "946--951",
journal = "Archives of General Psychiatry",
issn = "0003-990X",
publisher = "American Medical Association",
number = "10",

}

TY - JOUR

T1 - Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease

AU - Tiraboschi, Pietro

AU - Hansen, Larry A.

AU - Alford, Michael

AU - Merdes, Annette

AU - Masliah, Eliezer

AU - Thal, Leon J.

AU - Corey-Bloom, Jody

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Background: Reductions in cholinergic function occur in Alzheimer disease (AD) and dementia with Lewy bodies and correlate with cognitive decline. However, whether such alterations appear in early-stage disease is unclear. Objective: To examine the timing of cholinergic deficits in AD and dementia with Lewy bodies. Methods: Autopsy series of 89 patients with AD and 50 patients with the Lewy body variant of AD (LBV). Stage of disease was stratified according to results of the last Mini-Mental State Examination (MMSE) before death as mild, moderate, severe, or very severe. We analyzed choline acetyltransferase (ChAT) activity in the midfrontal, superior temporal, and inferior parietal cortices. Results: Although compared with a normal control group ChAT activity was decreased in the AD and LBV cohorts, ChAT activity reduction for the LBV cohort was much greater. Moreover, although the decline in ChAT activity in the AD cohort compared with the normal control group was significant only for patients in later stages of the illness, the decline in the LBV cohort was significant for those who died with mild-stage disease. When less impaired patients in each cohort (MMSE, ≥ 10) underwent separate analysis, the relationship of ChAT activity with the MMSE score was strong and significant for the LBV cohort alone. Conclusions: Although cholinergic deficits are seen in both AD and LBV, loss of ChAT activity is less severe and occurs later in the clinical course of AD. Conversely, in LBV, loss of ChAT activity is already prominent in the earliest stages of the illness, suggesting that cholinergic replacement therapy may be more effective in LBV than in AD, especially in mild-stage disease.

AB - Background: Reductions in cholinergic function occur in Alzheimer disease (AD) and dementia with Lewy bodies and correlate with cognitive decline. However, whether such alterations appear in early-stage disease is unclear. Objective: To examine the timing of cholinergic deficits in AD and dementia with Lewy bodies. Methods: Autopsy series of 89 patients with AD and 50 patients with the Lewy body variant of AD (LBV). Stage of disease was stratified according to results of the last Mini-Mental State Examination (MMSE) before death as mild, moderate, severe, or very severe. We analyzed choline acetyltransferase (ChAT) activity in the midfrontal, superior temporal, and inferior parietal cortices. Results: Although compared with a normal control group ChAT activity was decreased in the AD and LBV cohorts, ChAT activity reduction for the LBV cohort was much greater. Moreover, although the decline in ChAT activity in the AD cohort compared with the normal control group was significant only for patients in later stages of the illness, the decline in the LBV cohort was significant for those who died with mild-stage disease. When less impaired patients in each cohort (MMSE, ≥ 10) underwent separate analysis, the relationship of ChAT activity with the MMSE score was strong and significant for the LBV cohort alone. Conclusions: Although cholinergic deficits are seen in both AD and LBV, loss of ChAT activity is less severe and occurs later in the clinical course of AD. Conversely, in LBV, loss of ChAT activity is already prominent in the earliest stages of the illness, suggesting that cholinergic replacement therapy may be more effective in LBV than in AD, especially in mild-stage disease.

UR - http://www.scopus.com/inward/record.url?scp=0036792789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036792789&partnerID=8YFLogxK

M3 - Article

VL - 59

SP - 946

EP - 951

JO - Archives of General Psychiatry

JF - Archives of General Psychiatry

SN - 0003-990X

IS - 10

ER -