About alzheimer disease including definition, aetiology, stages, pathophysiology, diagnosis, treatment.

1. Presented by:- Ramesh Bhandari
IV pharm. D
T.V.M College of Pharmacy,Bellary..

2.  Are the mental disorders characterized by impaired
cognitive abilities and daily functioning.
 Involve disturbance in thinking/ memory.
 Brain is either damaged or injured.
 Neuro-degeneration due to age.
Two types of Cognitive Disorders:
 Dementia
 Amnesic disorder.
COGNITIVE DISORDERS.

3.  Alzheimer's disease is a gradually progressive form of
dementia occurring in middle age or later, characterized
by loss of short term memory, deterioration in behavior
and slowness of thought.
 It is most common type of dementia.50-70% cases of
dementia are diagnosed as Alzheimer’s Disease.

4. CONTINUE…
 It is believed that Alzheimer's disease
results from an increase in the production
or accumulation of a specific protein (beta-
AMYLOID protein) in the brain that leads to
nerve cell death.
 Generally, it is diagnosed in people over
65 years of age, although the less-
prevalent early onset of Alzheimer’s can
occur much earlier.

6. BRAIN DEGENERATION.

7. • AD is the most common
cause of dementia among
people age 60 and older.
• For every 5-year age group
beyond 45, the percentage
of people with AD doubles.
• 50-70% dementia are
Alzheimer’s Disease
patient.
EPIDEMIOLOGY
• By 2006, 26.6 million people’s in
world have AD ,and no preventive
treatments become available.
• Global: 29 million in 2010.

8.  Genetic, environmental, and lifestyle factors.
 Cholinergic effects have also been proposed.
 Occur by builting proteins in the brain. The
build-up manifests in two ways:
 PLAQUES– deposits of the protein -
amyloid accumulate in the spaces between
nerve cells.
 TANGLES – deposits of the protein
accumulate inside of nerve cells.

9. MAJOR RISK FACTORS .
 History of Stroke
 History of Neuropsychiatry
 Hypertension.
 Chain smoking.
 Alcohol
 LDL
 Diabetes
 Oxidative Stress.

10. ANATOMICAL CHANGES.

11.  Plaques are dense, mostly insoluble deposits of
amyloid –  peptides and cellular material outside
and around neurons.
 Tangles (neurofibrillary tangles) are aggregates of
the microtubule-associated protein and accumulate
inside the cells themselves.
 Although many older individuals develop some
plaques and tangles as a consequence of ageing.

12. PATHOPHYSIOLOGY
AMYLOID CASCADE HYPOTHESIS:-
Altered APP processing causes excess BAP production
BAP has got tendency to clump each other which gave rises to plaques
Plaques causes neurodegeneration & disturbance in impulse transmission
Finally this neuronal loss results in clinical sign and symptoms of
AD(Dementia)

13. NEUROFIBRILLARY TANGLES
NFTs are commonly found in the cells of the hippocampus and cerebral cortex in
persons with AD and are composed of abnormally hyperphosphorylated tau protein.
Tau proteins provide structural support to microtubules, and transportation of
nutrients.
When tau filaments undergo abnormal phosphorylation at a specific site
they cannot bind effectively to microtubules
and the microtubules collapse
Without an intact system of microtubules, the cell cannot function properly
eventually dies.
This neuronal loss results in clinical sign and symptoms of AD

14. CHOLINERGIC HYPOTHESIS:-
Multiple neuronal pathways are destroyed in AD.Widespread cell destruction results
in a variety of neurotransmitter deficits, with cholinergic abnormalities being the
most prominent.
In late AD, the number of cholinergic neurons is reduced, and there is loss of
nicotinic receptors in the hippocampus and cortex.
Presynaptic nicotinic receptors control the release of acetylcholine, as well as other
neurotransmitters important for memory and mood, including glutamate, serotonin,
and norepinephrine.
Finally resulting in dementia due to disruption in transmission of impulses between
neurons.
INFLAMMATORY MEDIATORS:-
The inflammatory/ immunologic hypotheses argue that although β AP may have
direct neurotoxicity, at least some of its toxicity might actually be an indirect
consequence of a β AP protofibril-induced microglia activation and astrocyte
recruitment. This inflammatory response may represent an attempt to clear amyloid
deposition. However, it is also associated with release of cytokines, nitric oxide, and
other radical species, and complement factors that can both injure neurons and
promote ongoing inflammation.

15. STAGES OF

16. 1) Early Stage/Mild Stage.
This is considered as a mild/early stage and the
duration period is 2-4 years.
Frequent recent memory loss.
Repeated questions, some problems expressing
and understanding language.
Writing and using objects become difficult and
depression and apathy can occur.

17. 2) Second stage/Moderate Stage
This is considered as a middle/moderate stage
and the duration is 2-10 years.
Rambling speech, unusual reasoning, confusion
about current events, time, and place.
Nearly 80% of patients exhibit emotional and
behavioral problems.
Slowness, rigidity, tremors.
Need reminders and assistance with activities of
daily living.

18. Continue……
 Increased memory loss and confusion.
 Inability to learn new things.
 Problems coping with new situations.
 Delusions .
 In moderate AD, damage occurs in areas of the
brain that control language, reasoning,
sensory processing, and conscious thought

19. 3) Severe.
 Duration is 1-3 years.
 Confused about past and present. Loss of
recognition of familiar people and places,Verbal
loss.
 Problems with swallowing and illness.
 Extreme problems with mood, behavioral
problems, hallucinations, and delirium.
 Patients need total support and care.

20. SUMMARY.

22. CLINICAL MANIFESTATIONS:-
Cognitive :-
■ Memory loss (poor recall and losing items)
■ Aphasia ( anomia)
■ Apraxia
■ Agnosia
■ Disorientation (impaired perception of time and unable to recognize familiar
people)
■ Impaired executive function
Noncognitive :-
■ Depression, psychotic symptoms (hallucinations and delusions)
■ Behavioral disturbances (physical and verbal aggression, motor hyperactivity,
uncooperativeness, wandering, repetitive mannerisms and activities, and
combativeness)
Functional :-
■ Inability to care for self (dressing, bathing, toileting, and eating)

23. Physicians today use a number of tools to diagnose AD:
• a detailed patient history
• information from family and
friends
• physical and neurological
exams and lab tests
• neuropsychological tests
• imaging tools such as CT scan,
or magnetic resonance
imaging (MRI).
• Confirming the diagnosis by
autopsy or biopsy of brain.
Diagnosing AD

24. CT SCAN SHOWS .

26. MANAGEMENT
 No specific treatment for AD.
 The primary goal of treatment in AD is to symptomatically treat
cognitive difficulties and preserve patient function as long as possible.
Secondary goals include treating the psychiatric and behavioral
sequelae that occur as a result of the disease.

27. (1) For cognitive symptoms:-
 Cholinesterase inhibitors :-
This kind of drug
postpones the worsening of symptoms for 6 to
12 years .
LOADING
MAINTENANCE
Rivastigmine 1.5mg BD 3-6mg twice
daily
Galantamine 4mg BD 8-12mg twice
daily

28.  Cholinergic drugs.Eg Acetyl-choline.
 Anti-glutamatergic Therapy:-
Memantine
(2) Non-cognitive symptoms:-
 Anti-deppressant Drugs(Paroxetine, Sertraline)
Fluoxetine 10-40mg/day
 Anti-Psychotic drugs (olanzapine,Risperidone)
Haloperidol 1-3mg/day
 Anti-convulsant Agent(Valproic acid)
carbamazepine 200-600mg/day

29. NON PHARMACOLOGICAL THERAPY:-
• Sleep disturbances, wandering, urinary incontinence, agitation, and
aggression should be managed with behavioral interventions
whenever possible.
• On initial diagnosis, the patient and caregiver should be educated on
the course of illness, available treatments, legal decisions, changes in
lifestyle that will be necessary with disease progression, and other
quality of life issues.
NOTE- Environment modification & Patient psycho-
Support are major point.

31. THANK YOU
Our vision is Alzheimer’s free world..
THANK YOU