Aging of the Nervous System: Functional Changes P.S.

Aging of the Nervous System: Functional Changes P.S.

Aging of the Nervous System: Functional Changes P.S. Timiras Acetylcholinesterase Inhibition Acetic acid Choline AChE inhibitor Presynaptic nerve terminal Muscarinic receptor

Postsynaptic nerve terminal Nicotinic receptor Acetylcholine (ACh) Nordberg A, Svensson A-L. Drug Safety. 1998;19:465-480. Acetylcholinesterase (AChE)

Again, in the normal aging brain the changes are relatively few. However impaired function and increased pathology do occur. Major functional deficits/ pathologies involve: Motility (e.g. Parkinsons Disease) Senses and communication Cognition (e.g. dementias) Affect and mood (e.g. depression) Blood circulation (stroke, multi-infarct dementia) rkinsons Disease: Chapter 8, pp. 110-113 mentias: Chapter 8, pp. 130-136 Control of Posture, Balance and Mobility

Central Nervous System Cerebral Cortex Basal Ganglia Cerebellum Vestibular-ocular & proprioceptive pathways Limbic System Spinal Cord Skeletal Muscles Bones and Joints Hormones Blood Circulation

aging, normal adult gait changes to: itant ad based ll stepped oped posture inished arm swings ns performed en bloc With Parkinsons, there is also: Rigidity Tremors (at rest) Akinesia (loss of power of movement) Bradykinesia (slowed movement) Pathology of Parkinsons entails:

Presence of Lewy bodies Loss of dopaminergic neurons in t substantia nigra Definition of Dementia Dementia (from the Latin de-mens, without mind) is a clinical syndrome that refers to a global deterioration of intellectual and cognitive functions characterized by a defect of all five major mental functions: Orientation Memory Intellect Judgment Affect

But with persistence of a clear consciousness. Dementia (cont.) There are two types of dementia: Reversible Irreversible TABLE 8-8 Type s of Co gnitive Impairment in t he Elderly to be Differentiated from Alzheimers Disease Delirium: an acute or subacute alteration of men tal status characterized by clouding of consciousness, fluctuationof

symptoms and improvement of men tal functionafter remova l of cause (reversible reversiblede m enti a). Depression : a speci fic psychiatricentity that can preced e or be associated withde m entia, and that can be d ifferentiall y diagnosed and treated. Benign Senescent Forgetfulness: not progressiveand not of sufficient severity to

interfere with everyday functions. Paranoid Statesand Psychoses: psychiatric diseases Amnesic Syndrome : short-term memory losses without delirium or dement ia. TABLE 8-7 Underlying and Reversible Causes of Dementia D E

M E N T I A Drugs Emotional disorders Metabolic or endocrine disorders Eye and ear dysfunctions Nutritional deficiencies Tumor and trauma Infections Arteriosclerotic complications

i.e., myocardial infarction, stroke or heart failure From Table 8.10 Anatomo-Histology Brain atrophy, flattening of gyri, widening of sulci, & cerebral ventricles Loss of cholinergic neurons, in nucleus of Meynert, hippocampus & association cortices Loss of adrenergic neurons, in locus

ceruleus Denudation of neurons, stripping of dendrites, damage to axons Increased microglia Pathology Accumulation of cell inclusions: lipofuscin, Hirano and Lewy bodies, altered cytoskeletal Tau proteins, ubiquitin Neurofibrillary tangles, neuritic plaques with amyloid, Perivascular amyloid, distributed throughout the brain, but especially

in frontal, prefrontal lobes, Hippocampus, association cortices Metabolism Decreased oxidative metabolism, slower enzyme activity (Ch. 7) Free-radical accumulation (Ch. 5) Impaired iron homeostasis (Ch. 7) Other minerals, zinc, aluminum Reduced level/metabolism/ activity of neurotransmitters

Increased amyloid b peptide with accumulation of amyloid proteins Increased prion protein Altered immune response TABLE 8-11 Genes Known to be Linked to A lzheimers Disease* Chromosomal Location Gene Type Age of Onset % Cases Familial

% Cases All 1 Presenilin 2 AD 40-70 yrs. 20 2-3

10 Risk factor > 60 yrs. ------ ------ 14 Presenilin 1 AD

30-60 yrs. 40-60 5-10 19 Apolipoprotein E4 Risk factor > 60 yrs. ------

40-50 21 APP Mutation ( APP) Downs Syndrome Trisomy AD 45-60 yrs. 2-3 <1

* Given the rapid progress in genetics, additional ge nes may be related to AD. TABLE 8-9 Characteristics of Multi-Infarct Dementia History of abrupt onset or stepwise deterioration History of transient ischemic attack or stroke Presence of hypertension or arrhythmia Presence of any neurologic focal symptoms or signs Learning at all Ages Induces Successful Aging TABLE 8-6 Mechanisms of Effect s of Increased Education on Successful Aging

Adequate income Better access to medical care Better access to recreational activity Good nutrition Responsible health behaviors Moderate alcohol intake Abstinence from smoking Possibility of increased brain reserve capacity More dendriticbranching,more synapses Better cerebral blood flow Better neural cell efficiency, adaptability, redundancy, survival and growth TABLE 8-12 Basic Goals of Alzheimers Disease Management

to main tain the patient'ss safet y while all owing as much independence and dignity as possible; to optimiz e the patients function by treating underlying medica l conditions and avoiding the use of drugs with side e ffects on the nervous system; to prevent stressful situations that may

cause or e xacerbate catastrophicreactions; to identify and manage complications that m ay arise from agitation, depression and incontinence; to provide medica land socialinformation to the patient'ss family in addition to any ne eded counselin g. For further information on brain plasticity in old age and factors which may enhance

this plasticity, see the below papers (full texts are available on the course website under Relevant Articles): Merabet LB et al. What blindness can tell us about seeing again: merging neuroplasticity and neuroprostheses. Nat Rev Neurosci 2005, 6(1) 71-77. Adlard PA et al. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. J. Neuroscience 2005, 25(17), 4217-4221. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 2003,

END Amyloidal Connection

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