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

2. Acetylcholinesterase Inhibition Nordberg A, Svensson A-L. Drug Safety. 1998;19:465-480. Postsynaptic nerve terminal Nicotinic receptor Presynaptic nerve terminal Muscarinic receptor Acetylcholine (ACh) Acetic acid Choline Acetylcholinesterase (AChE) AChE inhibitor

3. 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

4. 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

5. 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

7. 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.

8. Dementia (cont.) There are two types of dementia: –Reversible –Irreversible

13. 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 From Table 8.10

14. 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

15. 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

18. Learning at all Ages Induces Successful Aging

21. 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.

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24. Amyloidal Connection