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Early and Widespread Cholinergic Losses Differentiate Dementia With Lewy Bodies From Alzheimer Disease
Pietro Tiraboschi, MD;
Larry A. Hansen, MD;
Michael Alford, BA;
Annette Merdes, MD;
Eliezer Masliah, MD;
Leon J. Thal, MD;
Jody Corey-Bloom, MD, PhD
Arch Gen Psychiatry. 2002;59:946-951.
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.
From Neurologia, Ospedale San Paolo, Milano, Italy (Dr Tiraboschi);
the Department of Neurosciences, University of California– San Diego,
La Jolla (Drs Hansen, Merdes, Masliah, Thal, and Corey-Bloom and Mr Alford);
and the Neurology Service, San Diego Veterans Affairs Medical Center, San
Diego, Calif (Drs Thal and Corey-Bloom).
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