Alzheimer's disease (AD) is the most common form of dementia in older adults, characterized by a progressive decline in cognitive functions, including memory, thinking, and language. The disease's pathophysiology involves the abnormal accumulation of amyloid plaques and tau tangles in the brain, leading to neuronal damage and eventual brain shrinkage. While there is no cure for AD, treatments focus on symptom management, and lifestyle changes may reduce the risk of developing the disease.

1. ALZEIMER’S DISEASE

2. Welcome, in upcoming slides we will find out
following things about Alzheimer's disease:
Introduction
Causes
Pathophysiology
Sign and symptoms
Diagnosis
Medications
Treatment
Risk factors
So, let’s begin……….

3. Introduction
Alzheimer disease (AD) is the most common cause of dementia in the elderly
population. The disease usually manifests with the insidious onset of impaired
higher intellectual function and altered mood and behavior.
Later, this progresses to disorientation, memory loss, and aphasia, findings
indicative of severe cortical dysfunction, and over another 5 to 10 years, the
patient becomes profoundly disabled, mute, and immobile.
AD is characterized by a progressive decline in cognitive function. AD is
substantially increased among people aged 65 years or more, with a
progressive decline in memory, thinking, language and learning capacity. AD
should be differentiated from normal age-related decline in cognitive function,
which is more gradual and associated with less disability. Disease often starts
with mild symptoms and ends with severe brain damage. People with
dementia lose their abilities at different rates

4. Alzheimer's disease is caused by a combination of genetic, lifestyle and
environmental factors that affect the brain over time.
Less than 1 percent of the time, Alzheimer's is caused by specific genetic
changes that virtually guarantee a person will develop the disease. These
rare occurrences usually result in disease onset in middle age.
The exact causes of Alzheimer's disease aren't fully understood, but at its
core are problems with brain proteins that fail to function normally, disrupt
the work of brain cells (neurons) and unleash a series of toxic events.
Neurons are damaged, lose connections to each other and eventually die.
The damage most often starts in the region of the brain that controls
memory, but the process begins years before the first symptoms. The loss of
neurons spreads in a somewhat predictable pattern to other regions of the
brains. By the late stage of the disease, the brain has shrunk significantly.
https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447
CAUSES:

5. The pathophysiology of AD is related to the injury and death of neurons, initiating
in the hippocampus brain region that is involved with memory and learning, then
atrophy affects the entire brain.
7 Amyloid beta, also written Aβ, is a short peptide that is an abnormal proteolytic
byproduct of the transmembrane protein amyloid precursor protein (APP), whose
function is unclear but thought to be involved in neuronal development. Amyloid
beta monomers are soluble and contain short regions of beta sheet at sufficiently
high concentration, they undergo a dramatic conformational change to form a
beta sheet-rich tertiary structure that aggregates to form amyloid fibrils.
These fibrils deposit outside neurons in dense formations known as senile
plaques or neuritic plaques, in less dense aggregates as diffuse plaques, and
sometimes in the walls of small blood vessels in the brain in a process called
amyloid angiopathy or congophilic angiopathie.
.
https://www.who.int/medicines/areas/priority_medicines/BP6_11Alzheimer.pdf
PATHOPHYSIOLOGY

6. In Alzheimer disease abnormal aggregation of the tau protein, a microtubule-
associated protein expressed in neurons is also observed.
Tau protein acts to stabilize microtubules in the cell cytoskeleton. Like most
microtubule-associated proteins, tau is normally regulated by
phosphorylation.
In AD patients, hyper phosphorylated tau P-tau accumulates as paired
helical filaments that in turn aggregate into masses inside nerve cell bodies
known as neurofibrillary tangles and as dystrophic neurites associated with
amyloid plaques

7. Researchers are focused on the role of two proteins:
•Plaques. Beta-amyloid is a leftover fragment of a larger protein. When these
fragments cluster together, they appear to have a toxic effect on neurons and to
disrupt cell-to-cell communication. These clusters form larger deposits called amyloid
plaques, which also include other cellular debris.
•Tangles. Tau proteins play a part in a neuron's internal support and transport system
to carry nutrients and other essential materials. In Alzheimer's disease, tau proteins
change shape and organize themselves into structures called neurofibrillary tangles.
The tangles disrupt the transport system and are toxic to cells.
Image source- https://i2.wp.com/discoveryeye.org/wp-content/uploads/2017/11/alzheimer-brain.png?ssl=1

8. Image Source- https://www.keepmemoryalive.org/brain-science/alzheimers-brain

9. Neurobiological mechanisms involved in the pathogenesis of Alzheimers disease

10. The formation of plaques and tangles also prevents the production of some important
brain chemicals, called neurotransmitters (eg: acetylcholine, which is important in memory
function). Over time the loss of brain cells causes the brain to shrink.
While there is no known cause for Alzheimer's disease, some research studies have
indicated that the following factors may play an important role in the development of the
condition:
•Genetic factors, such as the presence of, or changes to, certain genes
•Environmental factors, such as long-term exposure to some environmental solvents
(eg: pesticides, glues and paints) or infection with certain viruses or bacteria
•Lifestyle factors, such as a lack of exercise, poor-quality sleep and a diet lacking fruit
and vegetables.
www.southerncross.co.nz/group/medical-library/alzheimers-disease-causes-
symptoms-prevention

11. Signs and symptoms
The degenerative changes that occur with Alzheimer's disease affect the
areas of the brain that control thought, memory and language resulting in
gradual signs and symptoms related to a person’s behaviour and mental
function. Often, physical functions such as bowel and bladder control are
also affected.
With Alzheimer’s disease there is great individual variability as to the
nature of symptoms experienced and the speed at which deterioration
occurs. The types of behaviour change and the length of time symptoms
are present are different for each person. The symptoms of Alzheimer's
disease typically develop quite slowly. The time between the onset of the
disease and death can range from five to 20 years.

12. Symptoms commonly experienced during the early stages of Alzheimer's disease
include:
•Mild forgetfulness – especially short-term memory loss
•Mood changes, including irritability and anxiety
•Difficulty processing new information and learning new things
•Loss of spontaneity and initiative
•Confusion about time and place
•Communication difficulties
•Decline in ability to perform routine tasks.
As Alzheimer’s disease progresses the following symptoms may develop:
•Increasing short-term memory loss and confusion
•Difficulty recognising family and friends
•Shorter attention span and feelings of restlessness
•Difficulty with reading, writing and numbers
•Possibly neglectful of hygiene
•Loss of appetite
•Personality changes (eg: aggression, significant mood swings)
•Requires increasing assistance with daily tasks.

13. Towards the later stages of the disease the following symptoms may be
experienced:
•Inability to understand or use speech
•Incontinence of urine / faeces
•Inability to recognise self or family
•Severe disorientation
•Increasing immobility and sleep time.
The changes brought about by Alzheimer's disease can be increasingly difficult for family
members and friends as the person’s condition deteriorates and they become unable to
recognise loved ones.
Although a person loses many abilities as the disease progresses, it is often helpful to focus
on the abilities that do remain, such as the senses of touch and hearing and the ability to
respond to emotion.

14. Diagnosis
There is a no single test to diagnose Alzheimer’s disease. Diagnosis
involves a full assessment of medical and psychiatric history to rule out
other possible causes. Therefore, a variety of tests are required to obtain
a conclusive diagnosis, which may include:
•A neurological and physical examination
•Blood and urine tests
•Brain scans
•Mental status assessment to determine the level of mental deterioration
•Caregiver interview to determine the level of dependency.
Scans to check brain structure and function may be recommended. The
different types of scans used may include CT scanning (computerised
tomography), MRI (magnetic resonance imaging) and PET (positron
emission tomography).

15. Medications
Medications such as sleeping tablets and tranquillisers may help to control symptoms
such as sleeplessness and agitation. However, they often cause increased confusion, so
their use should be limited.
A group of medications called cholinesterase inhibitors have shown some effectiveness in
slowing the progression of the condition in some people. These medications help prevent
the breakdown of acetylcholine, a neurotransmitter responsible for
memory. Cholinesterase inhibitor medications that are available in New Zealand include
donepezil, rivastigmine and galantamine.
More recently, another drug - memantine - has become available in New
Zealand. Memantine works in a different way to the cholinesterase inhibitors, aiming to
prevent the entry of an excess amount of calcium into brain cells. Higher than normal
levels of calcium in the brain cells causes damage to them and also prevents them from
receiving signals from other brain cells.
Research continues into the development of other medications for the treatment of
Alzheimer's disease. Medications being investigated include those that prevent the build-
up of amyloid deposits in the brain, as well as looking at the use of some anti-
inflammatory and hormone medications. Research also continues into the use of
alternative therapies such as anti-oxidants like Vitamin E, curcumin, selenium and some
herbal extracts (ginko balboas in particular).

16. Treatment
As there is no known cure for Alzheimer’s disease, treatment focuses on
managing symptoms and supporting the person and their family.
This may include:
•Treating medical conditions that may contribute to confusion or physical decline
eg: lung disease or anaemia
•Encouraging stimulating activities in order to encourage the person to continue
their normal activities as much as possible
•Providing memory aids and memory triggers such as calendars and written
reminders
•Encouraging social interaction to help prevent feelings of loneliness and
depression
•Contacting support groups that may be able to offer family/caregivers assistance
•Encouraging regular routine to reduce confusion
•No Smoking

17. Prevention / risk reduction
There are no proven ways to prevent the development of Alzheimer's
disease. However, there is epidemiological evidence to suggest that leading
a healthy lifestyle can reduce the risk of Alzheimer's disease.
Regular physical activity and exercise may have a general protective effect
on brain health and may slow progression of Alzheimer's disease.
Although there are no specific dietary specifications for Alzheimer's, a
Mediterranean-style diet (ie: plant foods such as vegetables, fruits, beans,
whole grains, nuts, olives and olive oil, along with some cheeses, yoghurt,
fish, poultry and eggs) may reduce the risk of Alzheimer's disease, and has
the added benefit of lowering cardiovascular disease and type2
diabetes risk. For more diet information, refer to our healthy heart diet.

18. https://www.who.int/medicines/areas/priority_medicines/BP6_11Alzheimer.pdf

19. Alzheimer Society of Canada (2016). Stages of Alzheimer's Disease (Web Page).
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s-disease/Stages-of-Alzheimer-s-disease [Accessed: 11/07/17]
Alzheimer Society of Canada (2016). Alzheimer's disease (Web Page). Toronto:
Alzheimer Society Canada. http://www.alzheimer.ca/en/About-dementia/Alzheimer-s-
disease [Accessed: 11/07/17]
Mayo Clinic (2015). Alzheimer’s disease (Web Page). Rochester, NY: Mayo
Foundation for Medical Education and Research. http://www.mayoclinic.org/diseases-
conditions/alzheimers-disease/home/ovc-20167098 [Accessed: 11/07/17]
Lakhan, S.E. (2017). Alzheimer disease (Web page). Medscape Drugs and Diseases.
New York, NY: WebMD LLC. http://emedicine.medscape.com/article/1134817-overview
[Accessed: 11/07/17]
Tobias, M, Yeh, L.C., Johnson, E. (2008). Burden of Alzheimer's disease: population-
based estimates and projections for New Zealand, 2006-2031. Aust NZ J Psychiatry;
42(9):828-36.