About alzheimer's disease

1. ALZHEIMERS
DISEASE
SAKINA

2. INTRODUCTION
ALZHEIMER DISEASE (AD) IS A
NEURODEGENERATIVE DISORDER MARKED BY
COGNITIVE AND BEHAVIORAL IMPAIRMENT
THAT SIGNIFICANTLY INTERFERES WITH SOCIAL
AND OCCUPATIONAL FUNCTIONING. IT IS AN
INCURABLE DISEASE WITH A LONG PRECLINICAL
PERIOD AND PROGRESSIVE COURSE. IN AD,
PLAQUES DEVELOP IN THE HIPPOCAMPUS, A
STRUCTURE DEEP IN THE BRAIN THAT HELPS TO
ENCODE MEMORIES, AND IN OTHER AREAS OF
THE CEREBRAL CORTEX THAT ARE INVOLVED IN
THINKING AND MAKING DECISIONS. WHETHER
PLAQUES THEMSELVES CAUSE AD OR WHETHER
THEY ARE A BY-PRODUCT OF THE AD PROCESS
REMAINS UNKNOWN. THE FOLLOWING IMAGE
DEPICTS ONE OF THE CARDINAL NEUROIMAGING
FINDINGS IN AD – HIPPOCAMPAL ATROPHY.

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CONTENT
INDEX

4. HISTORY
IN 1901, A GERMAN PSYCHIATRIST NAMED ALOIS
ALZHEIMER OBSERVED A PATIENT AT THE FRANKFURT
ASYLUM NAMED MRS. AUGUSTE D. THIS 51-YEAR-OLD
WOMAN SUFFERED FROM A LOSS OF SHORT-TERM
MEMORY, AMONG OTHER BEHAVIORAL SYMPTOMS
THAT PUZZLED DR. ALZHEIMER.
DR. ALZHEIMER SENT HER BRAIN AND HER MEDICAL
RECORDS TO MUNICH, WHERE HE WAS WORKING IN
THE LAB OF DR. EMIL KRAEPLIN. BY STAINING
SECTIONS OF HER BRAIN IN THE LABORATORY, HE
WAS ABLE TO IDENTIFY AMYLOID PLAQUES AND
NEUROFIBRILLARY TANGLES.

5. ANATOMY
PLAQUES
NFTs

6. NFT'S AND
PLAQUES

7. PATHOPHYSIOLOGY
Considerable attention has been devoted to elucidating the composition of SPs and
NFTs to find clues about the molecular pathogenesis and biochemistry of AD. The main
constituent of NFTs is the microtubule-associated protein tau . In AD,
hyperphosphorylated tau accumulates in the perikarya of large and medium pyramidal
neurons. Somewhat surprisingly, mutations of the tau gene result not in AD but in some
familial cases of frontotemporal dementia.
Since the time of Alois Alzheimer, SPs have been known to include a starchlike (or
amyloid) substance, usually in the center of these lesions. The amyloid substance is
surrounded by a halo or layer of degenerating (dystrophic) neurites and reactive glia
(both astrocytes and microglia).
AD affects the 3 processes that keep neurons healthy: communication, metabolism,
and repair. Certain nerve cells in the brain stop working, lose connections with other
nerve cells, and finally die. The destruction and death of these nerve cells causes the
memory failure, personality changes, problems in carrying out daily activities, and
other features of the disease.

8. Alzheimer disease biomarkers may follow a sequential pattern in
the brain, according to a study of AD biomarker trajectories. The
study included both symptomatic and asymptomatic carriers of
autosomal dominant gene mutations linked to AD, including APP,
PSEN1, and PSEN2. Researchers did not address tauopathy.
Results show that amyloid deposition in the brain occurs first,
followed by a decline in glucose metabolism and then structural
brain atrophy. The rate of Ab accumulation was significantly
higher in mutation carriers compared to noncarriers, and was
found to begin more than 2 decades before the expected onset of
dementia. In carriers, metabolism began to decrease at a mean
of 14.1 years before expected symptom onset, and structural
changes in the brain began 4.7 years before expected symptom
onset. It is important to note that only about 1% of patients with
AD have an autosomal dominant mutation, so results may not be
generalizable to sporadic AD.
PATHOPHYSIOLOGY

11. OTHER
HYPOTHESIS

12. ETIOLOGY
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13. CELLULAR
ETIOLOGY

14. Stages of
ALZHEIMER'S

15. THE PATHOLOGIC CHANGES ASSOCIATED WITH AD
BEGIN IN THE ENTORHINAL CORTEX, WHICH IS
NEAR THE HIPPOCAMPUS AND DIRECTLY
CONNECTED TO IT. AD THEN PROCEEDS TO THE
HIPPOCAMPUS, WHICH IS THE STRUCTURE THAT IS
ESSENTIAL TO THE FORMATION OF SHORT-TERM
AND LONG-TERM MEMORIES (SEE THE IMAGES
BELOW). AFFECTED REGIONS BEGIN TO ATROPHY.
THESE BRAIN CHANGES OCCUR DECADES BEFORE
ANY SIGNS OR SYMPTOMS APPEAR.
A PATIENT WITH PRECLINICAL AD MAY APPEAR
COMPLETELY NORMAL ON PHYSICAL EXAMINATION
AND MENTAL STATUS TESTING. AT THIS STAGE,
THERE IS NORMALLY NO ALTERATION IN JUDGMENT
OR THE ABILITY TO PERFORM ACTIVITIES OF DAILY
LIVING.
PRECLINICAL
STAGES 1

16. THE GROWING NUMBER OF PLAQUES AND TANGLES
FIRST DAMAGE AREAS OF THE BRAIN THAT
CONTROL MEMORY, LANGUAGE, AND REASONING
(SEE THE IMAGES BELOW). LATER IN THE DISEASE,
PHYSICAL ABILITIES DECLINE. THIS LEADS TO A
SITUATION IN MILD AD IN WHICH A PERSON SEEMS
TO BE HEALTHY BUT IS ACTUALLY HAVING MORE
AND MORE TROUBLE MAKING SENSE OF THE
WORLD AROUND HIM OR HER. THE REALIZATION
THAT SOMETHING IS WRONG OFTEN COMES
GRADUALLY BECAUSE THE EARLY SIGNS CAN BE
CONFUSED WITH CHANGES THAT CAN HAPPEN
NORMALLY WITH AGING.
MILD
STAGE 2

17. BEHAVIOR IS THE RESULT OF COMPLEX BRAIN
PROCESSES, ALL OF WHICH TAKE PLACE IN A
FRACTION OF A SECOND IN THE HEALTHY BRAIN.
IN AD, MANY OF THESE PROCESSES ARE
DISTURBED, AND THIS IS THE BASIS FOR MANY
DISTRESSING OR INAPPROPRIATE BEHAVIORS.
FOR EXAMPLE, PATIENTS MAY ANGRILY REFUSE
TO TAKE A BATH OR GET DRESSED BECAUSE
THEY DO NOT UNDERSTAND WHAT THE
CAREGIVER HAS ASKED THEM TO DO. IF THEY DO
UNDERSTAND, THEY MAY NOT REMEMBER HOW
TO DO WHAT WAS ASKED.
JUDGMENT AND IMPULSE CONTROL CONTINUE TO
DECLINE AT THIS STAGE. FOR EXAMPLE, TAKING
OFF CLOTHES MAY SEEM REASONABLE TO A
PERSON WITH AD WHO FEELS HOT AND DOES
NOT UNDERSTAND OR REMEMBER THAT
MODERATE
STAGE 3

18. IN THE LAST STAGE, SEVERE AD, PLAQUES AND
TANGLES ARE WIDESPREAD THROUGHOUT THE BRAIN,
AND AREAS OF THE BRAIN HAVE ATROPHIED FURTHER
(SEE THE IMAGES BELOW). PATIENTS CANNOT
RECOGNIZE FAMILY AND LOVED ONES OR COMMUNICATE
IN ANY WAY. THEY ARE COMPLETELY DEPENDENT ON
OTHERS FOR CARE. ALL SENSE OF SELF SEEMS TO
VANISH.
IN END-STAGE AD, PATIENTS MAY BE IN BED MUCH OR
ALL OF THE TIME. DEATH IS OFTEN THE RESULT OF
OTHER ILLNESSES, FREQUENTLY ASPIRATION
PNEUMONIA.
SEVERE
STAGE 4

19. All drugs approved by the US Food and Drug
Administration (FDA) for the treatment of AD modulate
neurotransmitters, either acetylcholine or glutamate. The
standard medical treatment for AD includes cholinesterase
inhibitors (ChEIs) and a partial N -methyl-D-aspartate
(NMDA) antagonist.
Secondary symptoms of AD (eg, depression, agitation,
aggression, hallucinations, delusions, sleep disorders)
can be problematic. Behavioral symptoms are common
and can exacerbate cognitive and functional impairment.
therapy, reversal of excess tau phosphorylation,
estrogen therapy, vitamin E therapy, and free-radical
scavenger therapy. Studies of these therapies have
yielded mostly disappointing results.
TREATMENT

20. MEDICATIONS
Donepezil has shown efficacy in
patients with mild to moderate AD, as
well as moderate to severe AD. It
selectively inhibits
acetylcholinesterase, the enzyme
responsible for the destruction of
acetylcholine, and improves the
availability of acetylcholine.
Donepezil's long half-life provides a
long duration of drug availability for
binding at the receptor sites.
Low- to moderate-affinity
uncompetitive N-methyl-D-
aspartate (NMDA) receptor
(NMDAR) antagonist that
binds preferentially to
NMDAR-operated cation
channels, blocking receptor
only under conditions of
excessive stimulation, with no
effect on normal
neurotransmission
amyloid and binds to aggregated
forms of beta-amyloid; preferentially
binds to parenchymal over vascular
amyloid. The FDA granted
accelerated approval for
aducanumab based on reduction in
amyloid beta plaques observed in
patients treated for Alzheimer
disease.

21. N0VELITY
Aducanumab (Aduhelm™) has received
accelerated approval as a treatment for
Alzheimer’s disease from the U.S. Food and
Drug Administration (FDA). This is the first FDA-
approved therapy to address the underlying
biology of Alzheimer’s disease.
It is the first therapy to demonstrate that
removing beta-amyloid, one of the hallmarks of
Alzheimer’s disease, from the brain is
reasonably likely to reduce cognitive and
functional decline in people living with early
Alzheimer’s.
Now, using a mouse model of Alzheimer's disease, a
team from Yale University in the US may have
figured out why the patches of protein seem relevant
without necessarily being directly responsible.
They found the swelling is formed by a buildup of
lysosomes – little bin-bag-like compartments created
by cells to break down waste and contain it until it
can be removed. These lysosomes clump into
spheroid structures along the axons of brain cells –
the long 'transmission cable' that extends from the
cell's body, and ends in branches of signal-sending
extensions.
Using calcium and voltage imaging of individual
cells, the team were able to show the amount of
signal disruption was linked to the spheroid sizes.
The spheroid swellings remain stable for long
periods of time, so likely continue to disrupt neuron

22. Patients counselling
WHEN COUNSELING PATIENTS FOLLOWING A DIAGNOSIS OF AD, IT IS ESSENTIAL TO
INVOLVE THE PATIENT’S FAMILY AND OTHERS WHO WILL PLAY A SUPPORTING ROLE IN
THE DISCUSSION. IT IS IMPORTANT TO EMPHASIZE THAT NOT ONLY THE PATIENT BUT
ALSO THOSE WHO SUPPORT THE PATIENTS WILL LIKELY EXPERIENCE REACTIONS OF
SADNESS AND ANGER AND THAT THESE ARE NORMAL REACTIONS TO SUCH A
DIAGNOSIS.
AS THE PATIENT’S SYMPTOMS BECOME MORE PRONOUNCED, A DIALOGUE MUST BE
OPENED REGARDING THE PATIENT’S WISHES FOR CARE WHEN HE OR SHE IS NO
LONGER ABLE TO MAKE THE NECESSARY CHOICES. DURABLE POWER OF ATTORNEY
SHOULD BE DISCUSSED, WITH PARTICULAR ATTENTION TO WHO WILL MAKE
DECISIONS FOR BOTH MEDICAL AND FINANCIAL ISSUES. MEDICAL ADVANCE
DIRECTIVES SHOULD BE CONSIDERED WHILE THE PATIENT IS STILL ABLE TO
PARTICIPATE IN THE DECISION-MAKING PROCESS.
THROUGHOUT THE COURSE OF THE DISEASE, FAMILY MEMBERS SHOULD BE CAREFUL
TO SELECT QUALIFIED AND TRUSTWORTHY INDIVIDUALS TO BE INVOLVED IN THE DAY-
TO-DAY MANAGEMENT OF THE PATIENT. CAREGIVERS NEED TO BALANCE ATTENTION
TO THE PATIENT’S PHYSICAL NEEDS WITH MAINTAINING RESPECT FOR THE PATIENT
AS A COMPETENT ADULT, TO THE EXTENT ALLOWED BY THE PROGRESSION OF THE
DISEASE. ANY SUSPICIONS OF ELDER ABUSE SHOULD BE IMMEDIATELY ADDRESSED.

23. Any questions?

24. THANK YOU