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Alzheimer’s Disease
Nicotine’s relationship and
contribution to dementia
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
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.
Hypotheses
Hypothesis #1
Nicotine is beneficial
to Alzheimer's disease
Alternate Hypothesis
Nicotine is harmful to
Alzheimer's patients
Null Hypothesis
Nicotine has no effects
whatsoever on Alzhiemer's
Two major theories on the cause
of Alzheimer’s disease
 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.
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.
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.
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.
N
CH3
N
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.
DA1
R1
DA2
R2
DA3
R3
DA4
R4
25
Range of Performance
24
23
22
21
full DA agonist
20
partial DA agonist
19
18
17
16
15
0.001
0.01
0.1
0.25
Dose (mg/kg)
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.
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.
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.
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.