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Cognitive Disorders
Dementia, Delirium and Psychotic
Progressive and degenerative CNS disorder
Nearly 50% of persons >85 years old have some
form of dementia
 Rates increasing as population ages
 Several types
◦ Alzheimer’s (most common type, may be a genetic
◦ Vascular
◦ General medical condition (e.g. Parkinson’s)
◦ Substances (e.g. alcohol)
◦ HIV/AIDS related
◦ Mixed or Unknown
Memory Impairment of Dementia
Difficulty learning new information
Forgetting learned information
Spatial disorientation
Poor judgment
Poor insight
Potential for violence
Loss of motor skills
Possible mood and sleep disturbances
Sometimes psychotic (delusional or hallucinatory)
experiences especially paranoia
Potentially Reversible Dementias
Toxic Causes
Alcohol, Polypharmacy, Illicit drugs
Electrolyte Disturbances
K+ loss, hepatic disease
Nutritional Causes
Prolonged neglect, B12 deficiency, malabsorption
syndrome, starvation
Respiratory infections, TB
Hypothyroidism, Pituitary insufficiency
Cerebral Disease
Brain tumor, multiple cerebral emboli, hydrocephalus
Alzheimer’s Dementia
60%-80% of cases of dementia are Alzheimer’s
type dementia (AD)
 >5.3 million people in the US have AD
 Characterized by the presence of amyloid plaques
on autopsy
◦ Mental deterioration is related to amount of plaque
Plaques interfere with cell-to-cell communication
 Plaques cause neurofibrillary tangles that collapse
 Result is a reduced availability of the
neurotransmitter ACh (acetylcholine) which is
associated with memory and learning
Amyloid Plaques (in rabbit cells)
Neurofibrillary Tangles
Lewy Body Dementia
Discovered by Frederic Lewy in 1913
 Often seen in late Parkinson’s disease
 Characterized by additional neuronal
lesions (colored cells) that are found in
the substantia nigra – an area that
controls unconscious muscle activity
 Onset of dementia is early – around age
60 years!
 20%-25% of cases have Lewy bodies
present on autopsy
Lewy Body Cells
Vascular Dementia
15-20% of all cases are vascular dementia
 Formerly called multi-infarct dementia
 Caused by multiple cerebrovascular
accidents (CVAs), or ‘strokes’
Vascular Dementia
Frontotemporal Lobar Dementia
 Formerly
called Pick’s Disease
 10% of dementia cases are FTLD
 Affects the frontal and temporal
 Causes changes in personality, social
skills, and emotions, behavior
disinhibition, and language
Frontotemporal Lobe Dementia
Prion (Creutzfeldt-Jakob) Disease
Rare disorder caused by spongiform
encephalopathy as a result of prions
 Prions are infectious proteins found in the CNS
of certain animals (cattle, deer) but also from
corneal transplants & human growth hormone
 Starts with confusion, depression and
progresses in weeks or months to dementia,
ataxia, palsy (involuntary jerky movements) and
sometimes blindness
 Occurs in 1per 1-million persons
Creutzfeldt-Jacob Disease
Down’s Syndrome Related Dementia
Down’s syndrome is 3
copies of chromosome
21 (trisomy 21)
Extensive amyloid
lesions found on autopsy
Early onset - 50% of
persons with Down’s
syndrome have dementia
symptoms onset around
age 40
Dementia is difficult to
diagnose if IQ is
substantially low
to start with
AIDS-related Dementia
HIV infection causes damage to neurons
involved with judgment, language, memory,
motor function and socialization
 Occurs in 40-60% of persons with HIV if
no treatment is provided*
 Minor cognitive motor disorder
associated with HIV is more common
Drugs for Alzheimer’s Disease
Pathophysiology of Alzheimer’s
Dementia Disorder
Degeneration of the cholinergic neuron
 Deficiency in ACh (Acetylcholine)
 Plaque formation outside of neurons and
in the cerebral cortex
 Beta-amyloid protein accumulation
 Presence of neurofibrillary tangles with
twists inside the neurons
 Some inflammatory (cytokine) response
Acetylcholinesterase Inhibitors
 “esterase”
indicates an enzyme reaction
that breaks down a molecule
 Acetylcholine – esterase refers to the
breakdown of Ach
 Inhibitors of ACh-esterase means that the
breakdown of ACh is blocked or reduced
thus leading to higher ACh levels
 AChE-inhibitors are the primary drugs to
treat Alzheimer’s dementia (not effective
in vascular dementia)
Primary ACh-E Inhibitors
PROTOTYPE: Aricept (donepezil)
◦ Most commonly prescribed drug, once daily
Exelon (rivastigmine)
◦ Available in a topical skin patch
Glanatamine (Razadyne)
◦ Derived naturally from daffodil bulbs
These drugs work by increasing ACh levels in the
neuron receptors. They are most effective in mild
to moderate Alzheimer’s as they slow cognitive
They do not stop the disease.
Side & Advers Effects of ACh-E
Side effects: GI - Nausea and diarrhea occur in
approximately 10% of clients
Administer with or without food.
Adverse effects: Bradycardia • Teach the family to
monitor pulse rate for the client who lives at home.
The client should be screened for underlying
heart disease.
 Should be used with caution in clients with preexisting asthma or other obstructive pulmonary
disorders as bronchoconstriction may be caused by
an increase of acetylcholine.
NMDA Receptor Antagonist
(Glutamate receptor blockade)
 Glutamate
is an excitatory
neurotransmitter. Excessive glutamate is
toxic to the brain and causes cell death.
 One drug, memantine (Namenda)
blocks excess glutamate by blocking the
entry of calcium into nerve cells, thus
slowing down brain-cell death.
 Namenda is approved in moderate to
severe Alzheimer’s disease and can
(perhaps should) be taken along with
ACh-E inhibitors.
Side Effects of memantine
 Headache
 Confusion
 Excitability/emotional lability
 Constipation
Memantine (Namenda) should not be used
in patients with renal disease
Alternative or
Gingko biloba is a plant that is thought
to improve memory.
◦ Gingko biloba may increase risk for bleeding
and have an additive effect with anticoagulants,
and it may increase the risk for seizures in
susceptible patients.
Antioxidants may be helpful due to their
anti-inflammatory effects (e.g. Omega 3
fatty acids “fish oil”).
Acute state of confusion and memory loss
Develops rapidly
Fluctuating course
Occurs in 10%-30% of hospitalized persons
Reversible Causes
◦ Medical condition (e.g. infection, head injury)
◦ Substance (e.g. opioids, other Rx meds, illicit
◦ Unknown
Risk factors: age, visual/hearing deficits, illness
Example: Delirium tremens in alcohol
Delirium may or may not have memory
 The individually is often agitated and
 Disorientation to place, time, even self
 May have hallucinations and delusions
 Delirium constitutes a major safety risk
for hospitalized patients
 Depending on the underlying cause,
delirium may be life-threatening
Schizophrenia & Other
Psychotic Disorders
History & Etiology of Schizophrenia
1800’s – described as dementia praecox
Bleuler coined the term schizophrenia, meaning “to
split”, and “the mind”
Not to be confused with multiple personality disorder
(now called dissociative identity disorder)
Occurs in 1% (1:100) of the population
<age 12 is rare (1:40,000)
Onset generally in late adolescence/early adulthood
Accounts for up to 50% of mental health care
Chronic disabling condition
Phases of Schizophrenia
Acute Phase
During this time, symptoms are prominent and
disabling and hospitalization may be required
Recovery & Maintenance Phase
Symptoms may be present but are less intense and
clients may live independently
Stable (Residual) Phase
Symptoms are in remission or are mild & chronic
1-2 years may elapse from the onset of
symptoms to first medical treatment
Other Psychotic Disorders
Schizoaffective disorder - a chronic condition where a
thinking disorder exists alongside a mood disorder such as
bipolar or major depression. Each must be treated
Substance-induced psychotic disorder - psychosis clearly
related to a substance, drug or medication. Cannot diagnose
schizophrenia until substance use is ruled out.
Psychotic disorder due to a medical condition – psychosis
from Pick’s disease, renal failure, dementia, fever, hypoxia,
hypothyroidism, etc. (any medical cause). Schizophrenia
cannot be diagnosed until all medical causes are ruled out.
Classification of Symptoms
Also called psychotic, or florid, symptoms
False perceptions (hallucinations)
False beliefs (delusions)
Bizarre (odd or eccentric) behavior
Confused or obsessive thoughts
Disorganized thoughts
Positive symptoms tend to respond to
dopamine blocking medications called
Classification of Symptoms
Apathy or indifference to others
Avolition – lack of motivation
Blunted or flat emotional affect
Loss of warmth or vibrancy in life
Poverty of thoughts – reduced thought variety
Alogia – poverty of speech
Anhedonia – loss of pleasure in things
Anergia – lack of energy
Negative symptoms are hard to treat but may
respond some to serotonin based medications.
These symptoms cause most of the disability of the disease.
Schizophrenia Simulator
Anderson Cooper experiences simulated
auditory hallucinations:
Pharmacology: Antipsychotic
Antipsychotic Medications are
Dopamine Antagonists
 Block
the activity of dopamine.
 Dopamine has 5 subtypes (D1-D5)
 D2 blockade results in motor (muscle) impairment
in the extra-pyramidal (motor) part of the brain.
This results in a side effect called extra-pyramidal
syndrome (EPS), or pseudo-Parkinsonism.
 Newer antipsychotics are weaker at D2 and
stronger at D4, and they also enhance serotonin
(5HT) levels similarly to an antidepressant.
These reduces side effects and improves negative
symptoms of schizophrenia.
Conventional Antipsychotics
Conventional antipsychotics are used to treat
mainly positive psychotic symptoms. They are
potent D2 blocking agents and thus are high in
neuromuscular side effects.
Chlorpromazine(Thorazine) – 1st one ever
PROTOTYE: Haloperidol (Haldol)
New-Generation (Atypical) Antipsychotics
Atypical antipsychotics are current preferred medications for psychotic disorders.
They generally treat both positive and negative symptoms.
Clozapine (Clozaril)
1st one on the market
 Olanzapine (Zyprexa)
 Quetiapine (Seroquel)
 Asenapine (Saphris)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Lurasidone (Latuda)
Iloperidone (Fanapt)
Paliperidone (Invega)
• Aripiprazole (Abilify)
Side effects of all Antipsychotics
• Extra-pyramidal
syndrome (EPS) ~ 11%
• Acute skeletal muscle
• Tardive dyskinesia
• Akathisia
• Neuroleptic Malignant
Syndrome (rare but life
• Hyperprolactinemia
• Hyperlipidemia
• Dry mouth
• Sedation
• Constipation
• Weight gain that
• Urinary
may be
associated with
the onset of Type II
• Orthostatic
The most common side effects for all
antipsychotics are dry mouth, constipation,
increased appetite, sedation and tremors.
Dopaminergic Adverse Events
EPS – tremors and sxs similar to Parkinson’s disease. Easily
treated with medications.
• Acute Dystonia – involuntary contractions of muscles.
Treated with PRN medications including injections.
• Tardive Dyskinesia – slow, sometimes writhing
movements of the muscles. Often around the face, head,
neck or trunk. Often irreversible and not responsive to
medication treatment.
• Akathisia – persistent need to get up and move, stretch,
walk around, rock. Difficult to treat and associated with
higher suicide completion rates.
• Neuroleptic Malignant Syndrome (rare but lifethreatening) – severe hyperthermia, decreased level of
consciousness, and hypertension associated with skeletal
muscle breakdown.
Drug-Induced Movement Disorders
Clinical Example of Tardive Dyskinesia caused
by an antipsychotic:
Treatment of Dopaminergic Effects
EPS and Acute Dystonias respond very well to the use of
anticholinergic medications:
Benztropine (Cogentin) – PO or IM
Trihexyphenidyl (Artane) – PO
Amantadine (Symmetrel) - PO
Diphenhydramine (Benadryl) – PO, IM or IV
• Some studies on the use of mega-doses of Vitamin E for
reducing or preventing tardive dyskinesia (800-1600 IU
• Akathisia is treated by reducing or changing the
antipsychotic or using:
-Propanolol (Inderal)
-Any of the Benzodiazepines for palliative relief
Dopamine blockage can affect prolactin levels
excreted by the pituitary gland resulting in a
drug-induced hyperprolactinemia
Signs of hyperprolactinemia:
• Breast enlargement
• Galactorrhea (breast milk production and secretion)
• Decreased menstruation
Patients who present with these symptoms
and are not pregnant, should have a prolactin
level drawn.
Some clinicians will also do an MRI to rule-out
pituitary gland tumor (either cancerous or
Histaminergic Side Effects
Of increasing concern are
Medication side effects related to histamine effects:
• Increased appetite
• Weight gain
• Hyperlipidemia
• Sedation, or tiredness
These side effects predispose the patient to obesity,
Type II DM, hypertension and heart disease.
Patients with chronic mental illnesses die an
average of 25-years earlier than the general
Other Antipsychotic Side Effects
All antipsychotics can lower seizure
threshold and increase risk for seizure
Clozapine (Clozaril) is associated with
significant drops in Absolute Neutrophil
Counts (a WBC) allowing opportunistic
infections that may be lethal. WBC/ANC
monitoring is required with this drug:
• Weekly for 6 month; then,
• Biweekly for 6 months; then,
• Monthly for life
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