Alzheimer PDF

ALZHEIMER’S DISEASE
DEFINITION: A progressive neurodegenerative disease and fatal dementia of unknown cause

characterized by loss of cognitive and physical functioning, commonly with behavior symptoms.
The patient becomes bed ridden at the end stage and eventually head towards death.
PATHOPHYSIOLOGY:
• β-amyloid protein aggregation, leading to formation of plaques.

• Hyperphosphorylation of tau protein, leading to neurofibrillary tangles.
• Synaptic failure and depletion of neurotrophin and neurotransmitters; loss of
cholinergic activity is most prominent.
• Mitochondrial dysfunction.
• Oxidative stress.
CLINICAL PRESENTATION:
• Cannot retain memory, forgetfulness (initial stages). Memory loss progresses with
neuronal loss, speech problem(aphasia) also depression, aggression, wandering,
psychotic symptoms may co-exist.
RISK FACTORS: Age, head injury, Down syndrome, depression, vascular disease, including
hypertension, elevated low-density lipoprotein cholesterol, low high-density lipoprotein
cholesterol, and diabetes.
TREATMENT STRATEGY:
• Donepezil, rivastigmine, and galantamine (Cholinesterase Inhibitors) are indicated in

mild to moderate AD. When switching from one cholinesterase inhibitor to another, 1-
week washout is generally sufficient.
• Abrupt discontinuation can cause worsening of cognition and behavior in some patients.
• Donepezil is also indicated for severe AD.
• Adverse effects of these drugs: Nausea, vomiting, diarrhea, bradycardia, muscle
weakness, urinary incontinence, dizziness, headache.
• Memantine blocks glutamatergic neurotransmission. It is used as monotherapy and in
combination with a cholinesterase inhibitor. It is indicated for treatment of moderate to
severe AD, but not for mild AD.
• Antipsychotics used: aripiprazole, olanzapine, and risperidone for disruptive behaviors
and neuropsychiatric symptoms.
• Selective serotonin reuptake inhibitor (SSRI) is usually given to depressed patients with
AD, sertraline and citalopram.
• Tricyclic antidepressants are usually avoided. Amitriptyline, Desipramine, Imipramine,
Nortriptyline.
BIPOLAR DISORDER
DEFINITION: It is a mood disorder characterized by extreme cases of happiness or manic

disorders or depressive episodes.
• Bipolar I disorder: at least one manic episode, and hypomanic or major depressive
episodes.
• Bipolar II disorder: at least one hypomanic episode and a depressive episode.
PATHOPHYSIOLOGY:
• Medical conditions such as CNS disorders, Infections, Electrolyte or metabolic

abnormalities (calcium or sodium fluctuations, hyperglycemia or hypoglycemia),
Endocrine or hormonal dysregulation.
• Medications, treatments may induce mania. Alcohol intoxication, Antidepressants,
Thyroid preparations, Hallucinogens (LSD), Xanthine (caffeine, theophylline).
• Environmental or psychosocial stressors (Bright light therapy, deep brain stimulation,
sleep deprivation) and immunologic factors are associated with bipolar disorder.
• Can be hereditary as well.
COURSE OF ILLNESS:
Mixed state- occur nearly every day for at least a 1-week period (major depressive episode
and a manic episode).
Rapid cyclers- have four or more episodes per year (major depressive, manic, or hypomanic).
They do not respond well to treatments. Usually associated with frequent and severe episode
of depression.
RISK FACTORS:
• Women are more likely to have increased depressive symptoms.

• Older age of onset. Episodes may become longer in duration and more frequent with
aging.
• Thyroid abnormalities.
• Men may have more manic episodes and substance use.
CLINICAL PRESENTATION: Different types of episodes may occur sequentially with or without a
period of normal mood (euthymia) between.
• MAJOR DEPRESSIVE EPISODE: >2-Week period of either depressed mood or loss of

interest or pleasure in normal activities. Delusions, hallucinations, and suicide attempts
are more common in bipolar depression. Decreased appetite, insomnia, decreased
energy or fatigue, impaired concentration and decision making, decreased interest in
normal activities.
• MANIC EPISODE: >1-Week period of abnormal and persistent elevated mood. Occurs
abruptly and increases day by day. Bizarre behavior (increased talking, racing thoughts)
hallucinations, and paranoid or grandiose delusions (increased self-esteem) may occur.
Causes: stressors, sleep deprivation, antidepressants, central nervous system (CNS)
stimulants, or bright light.
• HYPOMANIC EPISODE: At least 4 days of abnormal and persistent elevated mood. No
marked impairment in social or occupational functioning, no delusions, and no
hallucinations. Some patients may be more productive than usual, and may rapidly
switch to a manic episode.
TREATMENT STRATEGY:
• Bipolar patients should remain on a mood stabilizer (e.g., lithium, valproate,

carbamazepine) lifelong.
• Lithium is a first-line agent for acute mania, acute bipolar depression. Not effective as
maintenance therapy.
• Combination therapies (e.g., lithium plus valproate or carbamazepine; lithium or
valproate plus a second-generation antipsychotic) may provide better acute response
and prevention of relapse and recurrence than monotherapy.
• Divalproex sodium (sodium valproate), approved for acute manic or mixed episodes
and rapid cycling.
• Carbamazepine is commonly used for acute and maintenance therapy. It is usually
reserved for lithium-refractory patients, rapid cyclers, or mixed states.
• The combination of carbamazepine with lithium, valproate, and antipsychotics is often
used for manic episodes in treatment-resistant patients. Carbamazepine with
nimodipine can be beneficial for refractory patients.
• Oxcarbazepine is not FDA approved for treatment of bipolar disorder and has mood-
stabilizing effects similar to those of carbamazepine, but has fewer drug interactions
and milder side effects.
• Lamotrigine, effective for maintenance treatment of bipolar I and II disorder in adults,
has both antidepressant and mood-stabilizing effects.
• First- and second-generation antipsychotics, such as aripiprazole, asenapine,
haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone are effective as
monotherapy or as add-on therapy to lithium or valproate for acute mania.
• High-potency benzodiazepines (e.g., clonazepam and lorazepam) are commonly used
alternatives to antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or
in those who cannot take mood stabilizers.
• (IM) lorazepam may be used for acute agitation.
• Antidepressants commonly not used as they can worsen the manic situation.
• Prophylaxis with mood stabilizers (e.g., lithium or valproate) is recommended
immediately postpartum to decrease the risk of depressive relapse in bipolar women.
• When lithium is used during pregnancy, use the lowest effective dose to prevent
relapse.
• Breast-feeding is usually discouraged for women taking lithium but may breast feed
while taking valproate.

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ALZHEIMER’S DISEASE

DEFINITION: A progressive neurodegenerative disease and fatal dementia of unknown cause

• β-amyloid protein aggregation, leading to formation of plaques.

• Donepezil, rivastigmine, and galantamine (Cholinesterase Inhibitors) are indicated in

DEFINITION: It is a mood disorder characterized by extreme cases of happiness or manic

• Medical conditions such as CNS disorders, Infections, Electrolyte or metabolic

• Women are more likely to have increased depressive symptoms.

• MAJOR DEPRESSIVE EPISODE: >2-Week period of either depressed mood or loss of

• Bipolar patients should remain on a mood stabilizer (e.g., lithium, valproate,

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