DEFINITION:

• Alzheimer’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. 
• Alzheimer’s disease is Common in 5th and 6th decade
• Alzheimer’s disease is Atrophied gyri widened sulci
• Cortical atrophy of temporoparietal cortex

 ETIOLOGY:

• It is likely that the causes include genetic, environmental, and lifestyle factors.
•  Some drug therapies propose that AD is caused by reduced synthesis of the neurotransmitter acetylcholine.
• Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid leading to generalized neuroinflammation.
• Alzheimer’s disease is characterized by a build-up of proteins (Apo E gene) in the brain.
• Trisomy 21 is associated with alzheimer’s dementia
• Though this cannot be measured in a living person, extensive autopsy studies have revealed this phenomenon.
• The build-up manifests in two ways:
• Plaques– deposits of the protein beta-amyloid that accumulate in the spaces between nerve cells   
• Tangles – deposits of the protein tau that accumulate inside of nerve cells
• Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD.
• Plaques are dense, mostly insoluble deposits of amyloid – beta peptides and cellular material outside and around neurons.
• Senile neural plaques correlates (increases) with age
• Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves & are associated with severe dementia
• Lateral geniculate body is resistant to neurofibrillary tangles.

SYMPTOMS:

Early Stage

• This is considered as a mild/early stage and the duration period is 2-4 years.
• Frequent recent memory loss, particularly of recent conversations and events.
• Repeated questions, some problems expressing and understanding language.
• Writing and using objects become difficult and depression and apathy can occur.
• Drastic personality changes may accompany functional decline.
• Need reminders for daily activities and difficulties with sequencing impact driving early in this stage.

 Second stage

• This is considered as a middle/moderate stage and the duration is 2-10 years.
• Can no longer cover up problems. 
• Pervasive and persistent memory loss impacts life across settings.
• Dementia of Alzheimer’s type is associated with  Depressive symptoms, Delusions ,Apraxia and aphasia
• Rambling speech, unusual reasoning, confusion about current events, time, and place. 
• Potential to become lost in familiar settings, sleep disturbances, and mood or behavioral symptoms accelerate.
• Nearly 80% of patients exhibit emotional and behavioral problems which are aggravated by stress and change.
• Slowness, rigidity, tremors, and gait problems impact mobility and coordination. 
• Need structure, reminders, and assistance with activities of daily living.

Moderate stage

• Increased memory loss and confusion.
• Problems recognizing family and friends.
• Inability to learn new things.
• Difficulty carrying out tasks that involve multiple steps (such as getting dressed).
• Problems coping with new situations.
• Delusions and paranoia.
• Impulsive behavior.
• In moderate AD, damage occurs in areas of the brain that control language, reasoning, sensory processing, and conscious thought

 Last stage

• This is considered as the severe stage and the duration is 1-3 years.
• Confused about past and present. 
• Loss of recognition of familiar people and places
• Generally incapacitated with severe to total loss of verbal skills.
• Unable to care for self.  
• Falls possible and immobility likely.
• Problems with swallowing, incontinence, and illness.
• Extreme problems with mood, behavioral problems, hallucinations, and delirium.
• Patients need total support and care, and often die from infections or pneumonia

DIAGNOSIS 

• Patient history, collateral history from relatives, and clinical observations
• Characteristic neurological and neuropsychological features and the absence of alternative conditions.
• Computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computer tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.
• The fixative used in histopathology 10% buffered neutral formalin
• The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.

 TREATMENT: