Alzheimer’s Disease

It is a neurodegenerative disease that affects the brain, leading to impairment

of cognitive and behavioral function. It starts slowly and the disease process progresses over years

until symptoms are noticed. It accounts for 60-70% of cases of dementia. The

most common early symptom is usually found to be short term memory loss.

Alzheimer’s has become a serious health problem in the elderly demographic

in recent times. It was first described by Alzheimer in 1901. Over the last

decade, research on etiology and pharmacological treatment of Alzheimer’s

has been done in depth. Treatment focuses mainly on cholinergic therapy to

compensate for deficiency of Acetylcholine in the CNS.

SYMPTOMS

1. First symptoms affect complex activities of daily living. Short term

memory loss is the main symptom. Other symptoms include problems in

attentiveness, planning, impairment in abstract thinking and semantic

memory. Apathy is the most persistent symptom that is observed early

and seen throughout the course of the disease.

2. The preclinical stage of this disease is termed Mild Cognitive

Impairment. It is a transitional stage between normal ageing and senile

dementia. MCI with memory loss as primary symptom is called amnestic

MCI.

Early stage of Alzheimer’s disease

3. Early Stage: Early stage of Alzheimer’s disease sees progression of

learning and memory impairment to the point where it is definitively

diagnosed. Alzheimer’s affects the different memory capacities to

different extents. Episodic memory, Semantic memory and Implicit

memory is affected to a lesser extent than memory of new information.

Apraxia (difficulty in performing fine motor movements) and Agnosia are

noticed to a lesser extent.

Middle stage of Alzheimer’s disease

4. Middle Stage: Ability of subject to perform certain activities of daily

living become increasingly impaired. Behavioral and Neuropsychiatric

changes become more prevalent while language skills and fluency

declines significantly. Long term memory is first impaired in this stage.

Appearance of emotional instability, unpremeditated aggression,

irritability and wandering is seen. Sundown Syndrome, which is

characterized by increased confusion and restlessness is observed as

well.

Final stage of Alzheimer’s disease

5. Final Stage: This is the final stage of Alzheimer’s. The subject is

completely dependent on caretakers to perform activities of daily living.

Complete loss of speech along with extreme apathy and

exhaustion is noticed. The cause of death is due to external infections like

Pneumonia.

Etiology

The major neuropathological features of Alzheimer’s Disease is mostly

senile plaques and neurofibrillary tangles. The senile plaques seem to develop

first in brain areas associated with cognition and spread to other cortical areas

as the disease progresses. The senile plaques consist of insoluble deposits of

amyloid p-peptide (Amyloid beta), a fragment of the amyloid precursor protein

(APP). Amyloid beta peptide is generated from APP by two consecutive

cleavage events: proteolytic activity by β-secretase generates one end of the

Amyloid p-peptide, and γ-secretase generates the other end, also by

proteolysis.

Formation of neurofibrillary tangles is attributed to the accumulation of tau

protein, which is involved in maintaining stability of microtubules in axons of

neurons. Tau protein undergoes phosphorylation to stabilize the microtubules

in physiological conditions. In Alzheimer’s disease, Tau protein undergoes

change to become hyperphosphorylated. This leads to formation of new pairs

of microtubules linked together, creating the neurofibrillary tangles.

Mechanism

The mechanism of formation of amyloid plaques leading to Alzheimer’s disease

is not known well. A certain hypothesis says that the accumulation of beta

amyloid leads to neuronal degeneration. This occurs by disrupting the calcium

homeostasis of neurons, which in turn leads to release of cytochrome c from

mitochondria through formation of Mitochondrial Permeability Transition Pore

(MPTP). This triggers the intrinsic pathway of apoptosis by formation of

apoptosome complex by cytochrome c with other pro-apoptotic factors,

activating the caspase cascade, which mediates the process of apoptosis.

This cellular degeneration leads to destruction of cholinergic neurons, which

results in the pathology of Alzheimer’s disease. Inflammation and cytokines are

also said to play a role in the pathology of Alzheimer’s disease.

Psychosocial treatment

1. Psychosocial treatment

Environmental manipulation, family support, and prevention of other medical

comorbidities can improve functioning of patients. Changes in routine life like

daily remainders for performing daily activities and minimal focus on other

activities, concentrating on maintaining satiety, hydration, nutrition and

cleanliness.

Pharmacological treatment

2. Pharmacological treatment:

Administration of cognitive enhancers, antidepressants, antipsychotics, mood

stabilizers and hypnotics is followed to treat neuropsychiatric symptoms.

Treatment of cognitive disturbance

3. Treatment of cognitive disturbance:

Cholinesterase inhibitors, estrogen replacement therapy, anti-inflammatory

drugs and antioxidants like vitamin E and selenium in selegiline. Abrupt decline

in estrogen in post-menopausal women is one of the main reasons for

increased risk of Alzheimer’s disease in elderly women, as estrogen is shown to

play an important role in brain development and neuronal plasticity.

Treatment of behavioral disturbances

4. Treatment of behavioral disturbances:

Reversible monoamine oxidase inhibitors like brofaromine and moclobemide

are helpful in dealing with depression and dementia. Antidepressants like

fluoxetine, paroxetine and fluvoxamine are helpful in treating depression.

Risperidone is used as an antipsychotic drug to treat psychosis.