Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study.

BACKGROUND Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD. OBJECTIVE To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography. SETTING University and Veterans' Administration medical center. Design and Patients Group comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson disease without dementia (n = 11), and controls (n = 10) who underwent AChE imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had approximately equal dementia severity. MAIN OUTCOME MEASURES Cerebral AChE activity. RESULTS Compared with controls, mean cortical AChE activity was lowest in patients with PDem (-20.0%), followed by patients with Parkinson disease without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively preserved in patients with AD (-9.1%), except for regionally selective involvement of the lateral temporal cortex (-15%; P<.001). CONCLUSION Reduced cortical AChE activity is more characteristic of patients with PDem than of patients with mild AD.

[1]  C. Shute,et al.  Electron microscopy of cholinergic terminals and acetylcholinesterase-containing neurones in the hippocampal formation of the rat , 2004, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[2]  V. Bigl,et al.  Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's disease , 2004, Acta Neuropathologica.

[3]  K. Någren,et al.  Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[4]  S. Wisniewski,et al.  Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment , 2002, Annals of neurology.

[5]  Päivi Marjamäki,et al.  Choline acetyltransferase activity and striatal dopamine receptors in Parkinson's disease in relation to cognitive impairment , 2001, Acta Neuropathologica.

[6]  L. Thal,et al.  The decline in synapses and cholinergic activity is asynchronous in Alzheimer’s disease , 2000, Neurology.

[7]  David E. Kuhl,et al.  Kinetic Modeling of N-[11C]Methylpiperidin-4-yl Propionate: Alternatives for Analysis of an Irreversible Positron Emission Tomography Tracer for Measurement of Acetylcholinesterase Activity in Human Brain , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  I G McKeith,et al.  Report of the second dementia with Lewy body international workshop , 1999, Neurology.

[9]  S Tanada,et al.  Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson's disease and progressive supranuclear palsy , 1999, Annals of neurology.

[10]  K. Davis,et al.  Cholinergic markers in elderly patients with early signs of Alzheimer disease. , 1999, JAMA.

[11]  S. Minoshima,et al.  In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease , 1999, Neurology.

[12]  M. Mesulam,et al.  Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. , 1998, Brain : a journal of neurology.

[13]  D. Kuhl,et al.  Synthesis of 1-[11C]methylpiperidin-4-yl propionate ([11C]PMP) for in vivo measurements of acetylcholinesterase activity. , 1998, Nuclear medicine and biology.

[14]  Hitoshi Shinotoh,et al.  Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer's disease , 1997, The Lancet.

[15]  S. Minoshima,et al.  In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease , 1996, Annals of neurology.

[16]  C. Geula,et al.  Systematic regional variations in the loss of cortical cholinergic fibers in Alzheimer's disease. , 1996, Cerebral cortex.

[17]  K. Fukushi,et al.  Design and evaluation of radioactive acetylcholine analogs for mapping brain acetylcholinesterase (AchE) in vivo. , 1994, Nuclear medicine and biology.

[18]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

[19]  C. Geula,et al.  Acetylcholinesterase-rich pyramidal neurons in alzheimer's disease , 1992, Neurobiology of Aging.

[20]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[21]  J. Cummings,et al.  Alzheimer Disease and the Dementia of Parkinson Disease: Comparative Investigations , 1990, Alzheimer disease and associated disorders.

[22]  B. Reisberg,et al.  Global Deterioration Scale (GDS). , 1988, Psychopharmacology bulletin.

[23]  E. Perry,et al.  Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease. , 1985, Journal of neurology, neurosurgery, and psychiatry.

[24]  E. Perry,et al.  Pathological changes in the nucleus of meynert in Alzheimer's and Parkinson's diseases , 1983, Journal of the Neurological Sciences.

[25]  D L Price,et al.  Basal forebrain neurons in the dementia of Parkinson disease , 1983, Annals of neurology.

[26]  B. Reisberg,et al.  The Global Deterioration Scale for assessment of primary degenerative dementia. , 1982, The American journal of psychiatry.

[27]  Y. Agid,et al.  Muscarinic binding and choline acetyltransferase activity in Parkinsonian subjects with reference to dementia , 1982, Brain Research.

[28]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[29]  D M Bowen,et al.  Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. , 1976, Brain : a journal of neurology.