Pathology and Neurotransmitter Abnormalities of Dementia with Lewy BodiesDuda J.E.
Parkinson’s Disease Research, Education and Clinical Center, Philadelphia VA Medical Center, and the Department of Neurology, University of Pennsylvania, Philadelphia, Pa., USA
The neuropathology of dementia with Lewy bodies (DLB) is characterized by the presence of Lewy bodies (LBs) and Lewy neurites (LNs) in specific systems throughout the brainstem, diencephalon, basal ganglia and neocortex. DLB shares many features with Parkinson’s disease (PD) with respect to LB distribution in the brainstem, and there is recent evidence that Lewy pathology (LP), which consists of LBs and LNs, may progress in a systematic fashion through the brain regardless of clinical phenotype. Increasing evidence supports a central role for LNs in Lewy neurodegeneration and engenders a ‘neuritic dystrophy hypothesis’ described herein. LP formation also occurs in Alzheimer’s disease (AD) and other dementias, and it is unclear whether there is a common underlying pathophysiology in these diseases or if the LP merely represents a common final pathway. Cholinergic deficits are evident in both DLB and AD, with reductions in acetylcholine and abnormalities in nicotinic and muscarinic receptor expression in both diseases. Cholinergic deficits are greater in DLB than in AD, although generally there is less brain atrophy in DLB. The lower neurodegeneration and preservation of cholinergic receptors in DLB has important therapeutic implications because patients with DLB (vs. AD) may receive greater benefits from cholinergic pharmacologic therapy. Patients with DLB who display parkinsonian signs have severe dopamine neurotransmitter deficiencies similar to those in patients with PD, although the manifestation of these deficiencies is different. Both groups have striatal dopamine transporter deficiencies, but the striatal dopamine D2 receptors are reduced in DLB patients compared with PD and control subjects. D2 receptor deficiencies in DLB may be the cause of the relative lack of response to levodopa treatment and the severe adverse reaction to neuroleptics in these patients.
© 2004 S. Karger AG, Basel
John E. Duda, MD, Co-Director
Parkinson’s Disease Research, Education and Clinical Center
Philadelphia VA Medical Center, 3900 Woodland Avenue
Philadelphia, PA 19104 (USA)
Tel. +1 215 823 5934, Fax +1 215 823 5815, E-Mail John.Duda@med.va.gov
Number of Print Pages : 12
Number of Figures : 4, Number of Tables : 2, Number of References : 102
Dementia and Geriatric Cognitive Disorders
Vol. 17, No. Suppl. 1, Year 2004 (Cover Date: Released December 2003)
Journal Editor: V. Chan-Palay, New York, N.Y.
ISSN: 1420–8008 (print), 1421–9824 (Online)
For additional information: http://www.karger.com/journals/dem