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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 244 I. Bodis-Wollner and H. Moreno 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 . 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. 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. and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b. Dev Biol 240:641–653 Hinton VJ, Brown WT, Wisniewski K, Rudelli RD (1991) Analysis of neocortex in three