Alzheimer’s Disease

1. Alzheimer’s Disease Nicotine’s relationship and contribution to dementia

2. Characteristics of Alzheimer’s • Age related disorder • Shrinkage and loss of neurons • Accumulation of fibrillary materials and amyloid plaques • Deficiencies of acetylcholine and other neurotransmitters important in memory and learning processes

3. Adapted from www.brainalzheiemr’s.htm Overall shrinkage of brain tissue. Memory and judgment declines; emotional outbursts occur; routine tasks and language is impaired; progression of the disease leads to death of more cells and behavior changes. Loss of bowel and bladder control; complete dependency may last for years before the patient dies.

5. The Amyloid Cascade Theory: Neruodegenerative process is triggered by the abnormal accumulation of amyloid plaques. The Cholinergic Theory: Deficiencies of the neurotransmitter acetylcholine in the prefrontal cortex causes cognitive impairment. Two major theories on the cause of Alzheimer’s disease

6. The Amyloid Cascade Theory APP +  &  enzymes = A protein A lot of A proteins Amyloid plaques The Role of Nicotine in APP Nicotine enhances secretion of TTR, a gene that prevents accumulation of A proteins by binding to them. Declining levels of TTR are associated with dementia.

8. The Cholinergic Theory Cholinesterase Inhibitors are the compounds currently used to treat Alzheimer’s disease due to their ability to increase acetylcholine concentrations in the forebrain. Acetycholine plays a critical role in the formation and retrieval of memories and attention.

9. Role of Nicotine in Acetylcholine • Nicotinic receptors bind to acetylcholine. • Improve cognitive performance. • Prevent death of brain cells. • Delay cognitive decline in Alzheimer’s disease.

10. Other Neurotransmitters Systems • Nicotine increases dopamine release, a neurotransmitter critical in the proper functioning of the prefrontal cortex. • In Alzheimer’s, the dopamine system is affected, decreasing levels of the neurotransmitter in the cortex and in the hippocampus.

11. Adapted from Brioni • Dopamine agonists promote spatial working memory performance. • Studies show that only very small doses of the agents can achieve these improvements. • Excessive dopamine stimulation has been found to be harmful to prefrontal cortex function.

12. Nicotine also promotes the release of other neurotransmitters: norepinephrine and seratonin • Norepinephrine, as well as dopamine, has a vital influence on prefrontal cortex cognitive functioning. There is a 60% loss of norepinephrine neurons in aged primates and humans, and this loss is significantly increased in Alzheimer’s disease. • Some seratonin agonists are important in cognitive enhancement. They are used to manipulate other neurotransmitters systems such as acetylcholine, dopamine, and norepinephrine to alleviate behavioral and psychological symptoms in dementia.

13. Galanthamine • A water-insoluble alkaloid used to treat nervous system disorders. • Cognitive test scores of patients taking galanthamine improved. • Galanthamine has been found to improve memory by inhibiting an enzyme that breaks down acetylcholine and acts on the brain’s nicotinic receptors.

14. Conclusion • There is evidence showing improvement in cognitive performance in patients with Down’s syndrome and Parkinson’s disease when administered nicotine. • Studies state that nicotine can improve performance on a variety of tasks including learning, memory, and cognitive functioning. • Clinical observations show that long-term use of nicotine (i.e., smoking) is negatively correlated with risk for Alzheimer’s disease.