Alzheimer Disease

I: Biological correlates of Alzheimer disease.- 1: Alzheimer disease.- 1.1 Introduction.- 1.2 Differential diagnosis.- 1.2.1 Alzheimer versus frontotemporal dementias.- 1.2.1.1 Semantic dementia.- 1.2.2 Alzheimer versus dementia with Lewy bodies.- 1.3 Epidemiology.- 1.4 Risk factors.- 1.4.1 Smoking history.- 1.4.2 Sex.- 1.4.3 Head trauma.- 1.4.4 Cardiovascular risk factors.- 1.5 Psychiatric manifestations.- 1.6 Genetic susceptibility factors.- 1.7 Herpes simplex virus infections.- 1.8 Assessing outcome.- 1.9 Discussion.- 2: Neurological dysfunctions in Alzheimer disease.- 2.1. Introduction.- 2.2. Neurochemical studies.- 2.2.1 Senile plaques and neurofibrillary tangles.- 2.2.2 The ?-amyloid precursor protein.- 2.2.3 The amyloid cascade hypothesis.- 2.2.4 Selective vulnerability.- 2.3 Electrophysiological and imaging studies.- 2.3.1 Magnetic resonance imaging.- 2.3.2 Positron emission tomography.- 2.3.3 Magnetization transfer ratio.- 2.4 Discussion.- 3: Pharmacology of Alzheimer disease.- 3.1 Introduction.- 3.2 Cholinergic receptors.- 3.2.1 Cholinergic receptors and A? deposition.- 3.3 Monoaminergic receptors.- 3.3.1 Serotonin.- 3.3.1.1 Serotonin depletion studies.- 3.3.1.2 Serotonin transporter.- 3.3.1.3 Serotonin-cholinergic interaction.- 3.3.1.4 Serotonin receptors and psychotic symptoms.- 3.3.2 Noradrenaline.- 3.3.2.1 Noradrenergic-cholinergic interactions.- 3.3. 3 Dopamine.- 3.4 Glutamate and NMDA receptors.- 3.5 The cytokines.- 3.6 Cyclo-oxygenase enzymes.- 3.7 Metal-mediated oxy-radical and peroxide formation.- 3.7.1 Neuroinflammation.- 3.7.2 Oxidative stress.- 3.8 A? and endoplasmic reticulum-associated binding protein.- 3.9 A neurochemical marker for preclinical Alzheimer disease?.- 3.9.1 CSF tau.- 3.9.2 CSF cytokines.- 3.9.3 Choline acetyltransferase activity.- 3.9.4 Isoprostanes.- 3.9.5 Calcium.- 3.10 Serum anti-amyloid peptide antibodies.- 3.11 Discussion.- 4: Molecular genetics of Alzheimer disease.- 4.1 Introduction.- 4.2 Early onset Alzheimer disease.- 4.2.1 PS1 gene.- 4.2.2 PS2 gene.- 4.2.3 APP gene.- 4.2.4 Interleukin genes.- 4.3 Late-onset Alzheimer disease.- 4.3.1 Apolipoprotein E gene.- 4.3.2 Alpha-2 macroglobulin.- 4.4 Tau immunoreactivities.- 4.5 Genetic testing for Alzheimer disease susceptibility.- 4.5.1 Ethnic and racial differences.- 4.6 Discussion.- 5: Promises of animal models of Alzheimer disease.- 5.1 Introduction.- 5.2 Transgenic models of mutant human (Hu) APP with A? amyloid deposition.- 5.2.1 The Games mice.- 5.2.2 The Hsiao mice.- 5.2.3 The Novartis mice.- 5.2.4 The CT100 mice.- 5.2.5 Mutant presenilin mice.- 5.2.6 Hu APP over-expression on the ApoE null background.- 5.2.7 Hu APP over-expression combined with oxidative stress.- 5.2.8 APP knockout mice.- 5.2.9 PS1 knockout mice.- 5.3 Immunization with A?.- 5.4 Discussion.- II: Neuropsychology of Alzheimer disease.- 6: What is memory?.- 6.1 Introduction.- 6.2 Short-term memory, working memory and long-term memory.- 6.2.1 Short-term memory.- 6.2.2 Working memory.- 6.2.2.1 The central executive system.- 6.2.2.2 The phonological loop.- 6.2.2.3 The visuospatial sketchpad.- 6.2.2.4 The episodic buffer.- 6.2.3 Long-term memory.- 6.3 Declarative memory.- 6.3.1 Episodic memory.- 6.3.2 Semantic memory.- 6.3.3 Autobiographical memory.- 6.3.4 Prospective memory.- 6.4 Procedural memory.- 6.4.1 Skill learning.- 6.4.2 Repetition priming.- 6.5 Controlled and automatic memory process.- 6.6 Neuroanatomy and physiology of memory.- 6.6.1 Medial-temporal and diencephalic systems.- 6.6.2 The amygdala.- 6.6.3 The hippocampus.- 6.6.4 The frontal lobes.- 6.7 Amnesia.- 6.8 Mental imaging.- 6.9 Memory alterations in aging.- 6.10 Discussion.- 7: Mild cognitive impairment.- 7.1 Introduction.- 7.2 Boundary between normal aging and MCI.- 7.3 Neuropsychological markers.- 7.4 Eyeblink classical conditioning.- 7.5 A standardized clinical assessment?.- 7.6 Discussion.- 8: Cognitive impairment in Alzheimer disease.- 8.1 Introduction.- 8.2 Cognitive impairments.- 8.2.1 Executive function.- 8.2.2 Working memory deficit.- 8.2.3 Episodic memory deficit.- 8.2.4 Semantic memory deficit.- 8.2.5 Naming deficit.- 8.2.6 Intrusion errors.- 8.2.7 Visuo-spatial deficit.- 8.2.8 Language.- 8.2.9 Memory distortions.- 8.2.10 Implicit memory performance.- 8.3 Cognitive differences in neurodegenerative disorders.- 8.3.1 Typical Alzheimer disease.- 8.3.2 Frontotemporal dementia.- 8.3.2.1 Semantic dementia.- 8.3.3 Lewy body dementia.- 8.4 Discussion.- 9: Behavioral and psychological impairments.- 9.1 Introduction.- 9.2 Psychological impairment.- 9.2.1 Anxiety.- 9.2.2 Agitation and aggression.- 9.2.3 Depression.- 9.2.4 Psychosis.- 9.2.5 Sexual impairment.- 9.2.6 Delirium.- 9.2.7 Sleep disturbances.- 9.2.8 Wandering.- 9.2.9 Apathy.- 9.2.10 Alterations in dietary habit.- 9.3 Discussion.- 10: Assessment of memory.- 10.1 Introduction.- 10.2 Memory assessment.- 10.2.1 The Alzheimer Disease Assessment Scale — Cognitive Subscale.- 10.2.2 The Mini-Mental State Examination.- 10.2.3 The Blessed Dementia Scale.- 10.2.4 The Gottfries-Brane-Steen Scale.- 10.2.5 The Cambridge Mental Disorders of the Elderly Examination.- 10.2.6 The 7-minute neurocognitive screening battery.- 10.2.7 The Mattis dementia rating scale.- 10.2.8 The Brown-Peterson task.- 10.2.9 The Cognitive Drug Research Computerized Assessment System.- 10.2.10 Informant report questionnaire.- 10.3 Choice of an appropriate sensitive cognitive test.- 10.4 Discussion.- 11: Functional abilities and behavioral symptom assessments.- 11.1 Introduction.- 11.2 Functional abilities and activities of daily living assessment.- 11.2.1 Blessed-Roth dementia scale.- 11.2.2 Progressive deterioration scale.- 11.2.3 Interview for deterioration in daily living activities in dementia.- 11.2.4 AD Cooperative study-activities of daily living inventory.- 11.2.5 Alzheimer disease functional assessment and change scale.- 11.2.6 Disability assessment for dementia.- 11.3 Behavioral assessment.- 11.3.1 The dementia behavior disturbance.- 11.3.2 The eating behavior scale.- 11.3.3 Neuropsychiatric inventory.- 11.3.4 Behavioral pathology in Alzheimer disease rating scale.- 11.3.5 The Committee of the Consortium to establish a registry for Alzheimer disease.- 11.3.6 The MOUSEPAD.- 11.3.7 The Cohen-Mansfield agitation inventory.- 11.3.8 The geriatric mental state schedule.- 11.3.9 The geriatric depression scale.- 11.3.10 The Cornell scale.- 11.3.11 The consortium to establish a registry for AD behavior rating scale for dementia.- 11.4 Global function assessment.- 11.4.1 The clinical dementia rating scale.- 11.4.2 The global interview-based change scale.- 11.4.3 The global deterioration scale.- 11.4.4 AD cooperative study clinical global impression of change.- 11.4.5 Clinician’s global impression of change.- 11.5 Quality of life.- 11.5.1 Concept of utilities.- 11.6 Discussion.- III: Treatment of Alzheimer disease.- 12: Pharmacological treatments of cognitive deficits.- 12.1 Introduction.- 12.2 Modulation of the cholinergic system.- 12.2.1 Tacrine.- 12.2.2 Donepezil.- 12.2.3 Rivastigmine.- 12.2.4 Metrifonate.- 12.2.5 Galantamine.- 12.2.6 Controlled-release physostigmine.- 12.3 Nicotinic cholinergic strategies.- 12.4 Modulation of other neurotransmitter systems.- 12.4.1 Neurotrophic growth factors.- 12.4.2 Decreasing the cellular reaction to neurodegeneration.- 12.4.3 Propentofylline.- 12.4.4 Drugs that reduce oxidative stress.- 12.4.5 Estrogen replacement therapy.- 12.4.6 Therapeutic strategies in the APP/Ab amyloidgenic pathway.- 12.4.7 Anti-inflammatory drugs.- 12.4.8 Modulation of cholesterol homeostasis.- 12.4.9 Metal ion chelators.- 12.5 The emerging field of pharmacogenetics.- 12.6 Discussion.- 13: Pharmacological treatment of neuropsychiatric symptoms.- 13.1 Introduction.- 13.2 Depression.- 13.3 Psychosis.- 13.4 Anxiety.- 13.5 Discussion.- 14: Psychological support and cognitive rehabilitation.- 14.1 Introduction.- 14.2 Cognitive rehabilitation.- 14.2.1 Domain-specific knowledge.- 14.2.2 Errorless learning.- 14.2.3 Action-based memory.- 14.2.4 Reality orientation.- 14.2.5 Metacognition improvement.- 14.2.6 Spaced retrieval.- 14.3 Some other forms of treatment.- 14.4 Imagery mnemonics.- 14.5 External aids.- 14.6 Discussion.- 15: Discussion and conclusion.- References.