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Aging of the Nervous System: Functional Changes P.S. Timiras Acetylcholinesterase Inhibition Presynaptic nerve terminal Muscarinic receptor Postsynaptic nerve terminal Nordberg A, Svensson A-L. Drug Safety. 1998;19:465-480. 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. Parkinson’s Disease) Senses and communication Cognition (e.g. dementias) Affect and mood (e.g. depression) Blood circulation (stroke, multi-infarct dementia) Parkinson’s Disease: Chapter 8, pp. 110-113 Dementias: 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 With aging, normal adult gait changes to: •Hesitant •broad based •small stepped •Stooped posture •Diminished arm swings •Turns performed en bloc With Parkinson’s, there is also: •Rigidity •Tremors (at rest) •Akinesia (loss of power of movement) •Bradykinesia (slowed movement) Pathology of Parkinson’s entails: •Presence of Lewy bodies •Loss of dopaminergic neurons in the 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 T ABLE 8 - 8 Type s of Co gnitive Impa irment in t he Elderly to be Differentiated from Alzheime r’s Disea se Delirium: an acute or subacute alte ration of men t al status characterized by clouding of con sciousness, fluctuation of symptoms and improvement of men t al function after remova l of cause (reversible dementi a). Depression : a speci f ic psychiatric entity t hat can preced e or be associated with dementia, and t hat can be dif ferenti ally diagnosed and trea t ed. Benign Senescent Forgetfulness : not pr ogressive and not of sufficient severity to interfer e with ever yday functions. Paranoid States and Psychoses: psychiatric diseases Amnesic Syndrome : short -term memory dement ia. losses without delirium or T ABLE 8 - 7 Underlyin g and Rever sible Cau se s of Dementia D E M E N T I A Drugs Emotional disorders Met abolic or endocrine disorde rs Eye and ear dysfunctions Nutritional d eficienc ies T umor and trauma Infections Arteriosclerotic complications i.e., myocard ial inf arction, stroke or heart f ailure 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 peptide with accumulation of amyloid proteins Increased prion protein Altered immune response TABLE 8 - 9 Chara cteri stic s of Multi - Infarct Deme ntia Hist ory of abrupt onset or stepwise deter ioration Hist ory of transient ische mic at t ack or st roke Presence of hy pertension or arrhythmia Presence of any neurologic focal symptoms or signs Learning at all Ages Induces Successful Aging T ABLE 8 - 6 Mechani sms of Effect s of In crea sed Educat ion on Succe ssful Ag in g Adequate income Better access to medica l care Better access to recreational activity Good nu t rition Responsible he alth behaviors Moderate alcohol intake Abstinence from smoking Possibility of increased br ain reserve capacity More dendritic branching, more synapse s Better cerebra l blood flow Better neura l cel l ef ficiency, adap t ability, redundancy, su rvival and growth T ABLE 8 - 12 Ba sic Goal s of Alzheimer’ s Disea se Man agement to optimiz e the pat ient’s function by tre ating underlying medica l conditions and avoiding the use of drugs with side ef fects on the nervo us syst em; to prevent stressful situations that may exacerbat e ca t astrophic reactions; to identif y and ma nage complica t ions that may arise from agitation, depression and incontinence; to pr ovide medica l and social information to the pat ient's f amily in addition to any needed counseli ng. to main t ain th e pat ient's saf et y whi le all owing as much independence and dignity as possible; cause or 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, 14(2), 125-130. • van Praag H et al. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neuroscience 2005, 25(38), 8680-8685. END Amyloidal Connection