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Disorders: Parkinson’s Disease

and Alzheimer’s Disease

Ivan Bodis-Wollner and Herman Moreno

Abstract Among the most important neurodegenerative disorders affecting aging

adults around the world are Alzheimer’s disease (AD), which affects around 4.5 million people in the United States, and Parkinson’s disease (PD), which has a preva-lence of about 160 cases per 100,000 people and an incidence of about 20 cases per 100,000 people per year In both disorders prevalence and incidence increase with age AD is the main dementing disorder, whereas cognitive dysfunction and dementia eventually occur in 20–40% of patients with PD In this chapter the neuro-biology of these diseases is reviewed Classical, anatomically defined local circuits are summarized Data obtained using advanced imaging techniques, such as SPECT, and functional MRI, and electrophysiological recordings, are highlighted The main emphasis for both PD and AD is on cognitive deficits from the perspective of brain circuits and synaptic physiological abnormalities as well as on their biochemical correlates In particular, among nonmotor defects in Parkinson’s disease sensory deficits are also emphasized in relation to visuocogntive and attentive dysfunction The main neurotransmitter systems involved are dopamine (in PD) and acetyl-choline (both in PD and AD) The logic role of dopamine in the retinal circuitry

is discussed in relation to sensory (visual) dysfunction in PD The contribution of neurotransmitter/modulators beyond the dopaminergic and cholinergic systems in the basal ganglia and in several cortical areas is reviewed This involves glutamate, adenosine, and GABA The cognitive effect of genetic variability of catechol-o-methyltranferase, in the prefrontal cortex is summarized Although advances in the understanding of AD and PD pathophysiology have been significant, fundamental issues remain unsolved The powerful neuropathological arguments concerning the progression of PD based on alpha synuclein predict late involvement of cortical

I Bodis-Wollner (B)

Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA; Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA; Division of Movement Disorders, Department of Neurology, Parkinson’s Disease and Related Disorders Clinic, Center of Excellence NPF, Brooklyn, NY 11203, USA

e-mail: ivan.bodis-wollner@downstate.edu

243

J.P Blass (ed.), Neurochemical Mechanisms in Disease,

Advances in Neurobiology 1, DOI 10.1007/978-1-4419-7104-3_9,

C

Springer Science+Business Media, LLC 2011

circuits, presumably responsible for cognitive changes The role of acetylcholine and diverse cholinergic receptors in cognitive dysfunction in both AD and PD will need further studies Future studies may potentially lead to a bridging theory of cognitive impairment in both AD and PD.

Keywords Dopamine · Basal ganglia · Frontal cortex · Striatum · Vision · D1

and D2 dopamine receptors · Retina · Visual cognition · GABA · Subthalamic

nucleus · Cholinergic mechanisms · Glutamate · Adenosine · Thalamocortical

pro-cessing · Alzheimer’s disease (AD) · Mild cognitive impairment (MCI) · Amyloid

precursor protein (APP) · Amyloid beta (Aβ) tau · Apolipoprotein E ε4

(APOE4) · Cerebral blood volume (CBV) · Positron emission tomography

(PET) · Magnetic resonance imaging (MRI)

Contents

1 Introduction . 245

2 Parkinson’s Disease: An Overview . 246

3 Neurobiology of Parkinson’s Disease . 248

3.1 Etiology and Molecular Progression of PD . 248

3.2 PD as a Synucleinopathy . 248

4 Basal Ganglia Circuit . 249

4.1 Central Role of Dopamine in PD . 249

4.2 The Classical Basal Ganglia Circuit . 250

5 Frontal Cortices, Striatum, and Cognition in PD . 252

5.1 Fontostriatal Circuits in PD . 252

5.2 Impaired Memory in PD: Thalamocortical Circuitry . 253

5.3 Genetic Variability of Catechol-O-Methyltranferase, Prefrontal Cortex, and Cognition . 255

6 Vision and Visual Cognition . 256

6.1 Short-Term Memory for Visual Stimuli and Spatial Orientation in PD . 256

6.2 Aging and Cognitive Event-Related Potentials . 259

6.3 Neurotransmitters and Cognitive ERP-S in PD . 259

6.4 Dopamine in Visual Processing in the Retina . 260

6.5 Retinal Model of Dopaminergic Dysfunction in PD . 262

7 Nondopaminergic Signals and Cognition in PD . 265

7.1 GABA and the Subthalamic Nucleus . 265

7.2 Cholinergic Mechanisms . 266

7.3 Glutamate, Thalamocortical Processing, and D1 and D2 Dopamine Receptors 267 7.4 Adenosine . 268

8 The Alzheimer’s Disease Case: An Overview . 269

9 Cognitive Decline in the Elderly; Is It “Aging”, MCI, or Early AD . 270

9.1 Normal Aging . 270

9.2 Mild Cognitive Impairment (MCI) . 272