P. HarshithaPharm.D IV year

Definition, Etiology, Clinical manifestations, pathophysiology

INRODUCTIONAlzheimer’s disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory and eventually by disturbances in reasoning, planning, language, and perception.

AD is also known as senile dementia of the Alzheimer type (SDAT) or simply Alzheimer's the most common form of dementia. It is an incurable, degenerative, terminal disease.

AD results from an increase in the production or accumulation of specific protein (β-amyloid protein) in the brain that leads to nerve cell death

ETIOLOGY

• The exact etiology of Alzheimer’s disease is unknown and associated with risk factors

• But stated that there are several GENETICAL and ENVIRONMENTAL factors have been explored as potential causes of the Alzheimer’s disease

RISK FACTOR for developing the Alzheimer's disease

• Increased age (over 65 years of age)• Hypertension (high blood pressure)• Increased cholesterol levels• Coronary artery disease• Diabetes

OTHER risk factors are

• Genetics• Smoking and alcohol use• Plasma homocysteine• Down syndrome• Mild cognitive impairment

PATHOPHYSIOLOGY

There are two signature lesions in Alzheimer’s Disease. They are

1. Neuritic Plaques: Deposits of β- amyloid protein that accumulates in the spaces between the nerve cells.

2. Neurofibrillary Tangles (NFT’s): Deposits of the protein tau that accumulates inside the nerve cells

NEURITIC PLAQUES:Cleared by β-secretase mutation of amyloid precursor -secretase protein on chromosome no 21

secretase has two genes 1 & 2,When these undergoes mutation increased production of amyloid They lead to increased cleaving of precursor protein secretase. These sed cleavingof APP results in increased production of β- amyloid protein Produces of amyloid protein

Accumulation of β amyloid protein (due to increased production of APP)

Directly neurotoxin Alzheimer’s disease

NEUROFIBRILLARY TANGLES

Neurons have an internal support structure partly made up of microtubules. A protein called tau helps stabilize microtubules.

In AD, tau changes, causing microtubules to collapse, and tau proteins clump together to form neurofibrillary tangles.

SYMPTOMS

COGNITIVE:• Memory loss• Aphasia• Apraxia• Agnosia• Disorientation• Impaired executive function

NON COGNITIVE• Depression, psychotic symptoms(hallucination and delusions)• Behavioral disturbances(physical and verbal aggression, motor

hyperactivity, uncooperativeness, wandering, repetitive mannerisms and activities, and combativeness)

FUCTIONAL• Inability to care for self (dressing, bathing, toileting, and eating)

STAGES OF ALZHEIMER’S DISEASE

EARLY MILD MODERATE SEVERE

DURATION:

2-4 years 2-10 years --- 1-3 years

SYMPTOMS:• Recent memory

loss• Repeated

questions• Problems with

language• Depression• Apathy• Personality

changes• Need

reminders for daily activities

• Persistent memory loss

• Rambling speech

• Unusual reasoning

• Confusion• Sleep

disturbance• Mood &

behavioral changes

• Slowness• Rigidity• Tremors• Gait

• Increased memory loss and confusion

• Inability to learn things

• Delusions• Paranoia• Problems

recognizing family and friends

• Total loss of verbal skills

• Unable to care for self

• Falls possible and immobiling likely

• Problems with swallowing

• Incontinence and illness

• Hallucinations and delusions

• Patient needs total care and support

DIAGNOSIS Detailed patient history

Information from family and friends

Laboratory tests like• Rule out vitamin B12 and folate deficiency• Rule out hypothyroidism with TFT tests• Blood cell count, serum electrolytes, LFT

Other diagnostic tests• CT,PET or MRI scans may aid diagnosis

PET SCAN

REFERENCE Principle of Pharmacotherapeutics by

Joseph.Dipiro

Textbook of Pathophysiology by Harsh Mohan

...Thank you…