NEUROCOGNITIVE

DISORDERS
COGNITION:

Memory
Language
Orientation
Judgment
Conducting interpersonal relationships
Performing actions (praxis)
Problem solving
• DELIRIUM
• DEMENTIA
• OTHER AMNESTIC DISORDER
• MILD COGNITIVE IMPAIRMENT

DELIRIUM
• Marked by short term
confusion and changes in
cognition;
• Subcategories:
• GMC (infection)
• Substance-induced
• Multiple causes
• Other or multiple etiologies
(sleep deprivation,
meditation)
AMNESTIC
DEMENTIA
DISORDERS
• Major Neurocognitive • Major Neurocognitive
Disorder Disorder caused by other
• Marked by severe medical conditions
impairment in memory, • Marked primarily by
judgment, orientation and memory impairment in
cognition. addition to other
• Subcategories: cognitive symptoms.
• Alzheimer’stype • Causes:
• Vascular dementia • Medical conditions
• HIV dementia (hypoxia)
• Head trauma • Toxins and medications
• Pick’s disease • Unknown causes
• Prion disease
• Substance-induced
• Multiple etiologies
• Not specified
CLINICAL EVALUATION:
I. HISTORY TAKING

detailed rendition of patient’s changes in daily routine: self care, job

responsibilities, meal preparations, shopping and personal support, interaction with
friends, ability to maintain personal finances

Particular pursuit that is central to patient and impact of illness

Patient-specific baseline for monitoring the effects of future therapies.

CLINICAL EVALUATION:
II. MENTAL STATUS EXAMINATION

A means of surveying functions and abilities to allow a definition of personal

strengths and weaknesses.
Repeatable, structured assessment
Promotes effective communication among physicians
Establishes basis for future comparison
Essential for documenting therapeutic effectiveness
Allows comparisons between different patients
CLINICAL EVALUATION:
III. COGNITION

Memory
Visuospatial and constructional abilities
Reading, writing and mathematical abilities
Abstraction
CLINICAL EVALUATION:
A. General Description D. Mood and Affect
1. General Appearance, dress, sensory aids 1. Internal mood state; sense of humor

2. Level of consciousness and arousal 2. Future outlook

3. Attention to environment 3. Suicidal ideas and plans

4. Demo emotional status
4. Posture(standing and seated)
5. Gait E. Insight and Judgment
6. Movements of limbs, trunk, and face 1. Self appraisal and self esteem
2. Understanding of current circumstances
7. General demeanor
3. Ability to describe personal psychological and physical status
8. Response to examiner
4. Appraisal of major social relationships
9. Native or primary language
5. Understanding of personal roles and responsibilites
B. Language and Speech
F. Cognition
1. Comprehension
1. Memory 8. Finger gnosis
2. Output
2. Visuospatial skills 9. Right-left orientation
3. Repetition
3. Constructional ability 10. executive functions
4. Other aspects: object naming, color naming, body part
4. Mathematics 11. abstraction
identification, ideomotor praxis go command
5. Reading
C. Thought
6. Writing
1. Form
7. Fine sensory function
2. Content
CLINICAL EVALUATION:
IV. SCREENING LABORATORY TESTS
GENERAL TESTS ANCILLARY LABORATORY TESTS
CBC Blood cultures Nocturnal penile tumescence
Erythrocyte sedimentation rate Rapid plasma regain test CSF glucose, protein
Electrolytes HIV testing CSF cell count
Glucose Serum heavy metals CSF culture
BUN, Crea Serum copper Cryptococcal antigen
Liver function tests Ceruloplasmin VDRL test
Serum calcium and phosphorus Serum B12 RBC folate levels CT scan
Thyroid function tests Urine culture MRI
Serum protein Urine toxicology PET
Drugs levels Urine heavy metal screen SPECT
Urinalysis EEG
Pregnancy test Evoked potentials
ECG polysomnography
CLINICAL EVALUATION:
V. NEUROPSYCHOLOGICAL TESTING

Provides a standardized, quantitative, reproducible evaluation of a patient’s

cognitive abilities

For initial evaluation and periodic assessment

DELIRIUM:
 characterized by an acute decline in both the level of consciousness and cognition
with particular impairment of attention.

Hallmark symptom: IMPAIRMENT OF CONSCIOUSNESS

Life threatening, potentially reversible

Abnormalities of mood, perception, and behavior are common psychiatric

symptoms;

tremor, asterixis, nystagmus, incoordination, and urinary incontinence are common

neurological symptoms
DELIRIUM:
Intensive care unit psychosis
Acute confusional state
Acute brain failure
Encephalitis
Encephalopathy
Toxic metabolic state
Central nervous system toxicity
Paraneoplastic limbic
encephalitis
Sundowning
Cerebral insufficiency
Organic brain syndrome
DELIRIUM: EPIDEMIOLOGY
In community studies: 1% of
General surgery: 10-15%
elderly age 55 years and above
 (13% of these are in the 85 years or
Open heart surgery: 30%
older group) Hip fractures : >50%
Elderly Emergency dept patients:
ICU patients: 70-87%
10% reported to have delirium
End of life care: 83%
At the time of admission to medical
wards: b/w 15 and 21% of older Nursing home or postacute care
patients meet criteria for delirium settings: 60%
For patients with no delirium at Severe burns: 21%
time of admission : 5-30% with
AIDS during hospitalization: 30-
subsequent cases of delirium
40%
during hospitalization
Terminally ill patients: 80%
DELIRIUM: EPIDEMIOLOGY

CAUSES OF POST-OP DELIRIUM:

1. Stress of surgery
2. Postoperative pain
3. Insomnia
4. Pain medications
5. Infection
6. Fever
7. Blood loss
DELIRIUM: EPIDEMIOLOGY
P RE DI S P O S I N G FA C TO R S P R E C IP ITAT IN G FA C TO R S
DEMOGRAPHIC CHARACTERISTICS • DRUGS : sedative hypnotics, narcotics,
• Male, 65 yrs and older anticholinergics, multiple drugs; alcohol or drug
withdrawal
COGNITIVE STATUS : Dementia, cognitive
impairment, history of delirium, depression
• PRIMARY NEURO DSES: stroke,
nondominant hemisphere; IC bleeding; meningitis/
FUNCTIONAL STATUS : functional encephalitis
dependence, immobility, hx of falls, low level of activity
• INTERCURRENT ILLNESSES: infections,
SENSORY IMPAIRMENT: hearing, visual iatrogenic complications, severe acute illness,
hypoxia, shock, anemia, dhn, poor nutritional status,
DECREASED ORAL INTAKE: dhn,
hypoalbuminemia, metabolic derangements
malnutrition
• SURGERY: orthopedic, cardicac, prolongedCP
DRUGS: psychoactive, anticholinergics, alcohol
bypass, noncardiac surgery
abuse
• ENVIRONMENTAL: ICU, physical restraints,
COEXISTING MEDICAL CONDITIONS:
bladder catheter, multiple procedures, pain, emotional
severe medical diseases metabolic derangement
stress, prolonged sleep deprivation.
Chronic renal/hepatic dse HIV; terminal dses.
DELIRIUM: EPIDEMIOLOGY
Poor prognostic sign
Rates of institutionalization increased threefolds for patients 65 years and
older who exhibit delirium while in the hospital
Mortality rates:
– 23 – 33 % - 3-month mortality rate
– 50% - 1 year mortality rate
– 20 – 75 % - mortality rate during that hospitalization for elderly patients
• After discharge – 15% 1 month mortality rate
• 25% within 6 months
DELIRIUM: ETIOLOGY
Major causes of delirium :

1. central nervous system disease (e.g., epilepsy)

2. systemic disease (e.g., cardiac failure)

3. either intoxication or withdrawal from pharmacological or

toxic agents
DELIRIUM: ETIOLOGY
Common causes of delirium :

CNS DISORDERS Seizure (postictal, nonconvulsive status, statuse

epilepticus);Migraine; Head trauma, brain tumor, SAH, subdural
hematoma, abscess, IC hge, cerebellar hge, nonhrgic stroke,
transient ischemia
METABOLIC DISORDERS Electrolyte abnormalities, DM, hypoglycemia, hypergycemia, or
insulin resistance
SYSTEMIC ILLNESSES Infection(e.g. sepsis, malaria, erysipelas, virl, plague,Lyme dse.,
syphilis, or abscess); Trauma, dhn or vol overload, nutritional
def., burns, uncontrolled pain, heat stroke, high altitude
(>5000m)
MEDICATIONS Pain meds(Demerol, or morphine), antibiotics, antivirals, and
antifungals; antihypertensives; steroids, anesthesia, cardiac meds,
antineoplastics, anticholinergics, NMS, serotonin syndrome
OVER THE COUNTER PREPS Herbals, teas, nutirtional supplements
DELIRIUM: ETIOLOGY
Common causes of delirium :

BOTANICALS Jimsonweed, oleander, foxglove, hemlock, dieffenbachia,

Amanita phalloides
CARDIAC Cardiac failure, arrythmia, MI, cardiac assist device, cardiac sx
PULMONARY COPD, hypoxia, SIADH, acid-base disturbance
ENDOCRINE Adrenal crisis/failure, thyroid abn, PTH abn
HEMATOLOGICAL Anemia, leukemia, blood dyscrasia, stem cell transplant
RENAL Renal failure, uremia, SIADH
HEPATIC Hepatitis, cirrhosis, hepatic failure
NEOPLASMS Primary brain, metastases, neoplastic syndromes
DRUGS OF ABUSE Intoxication and withdrawal
TOXINS Intoxication and withdrawal; heavy metals and aluminum
DELIRIUM: DSM V DIAGNOSTIC
CRITERIA
A. A disturbance in attention(i.e., reduced ability to focus, direct, sustain, and shift attention), and
awareness (reduced orientation to the environment).
B. The disturbance develops over a short period of time, represents a change from baseline attention and
awareness, and tends to fluctuate in severity during the course of the day.
C. An additional disturbance in cognition (e.g. memory deficit, disorientation, language, Visuospatial
ability, or perception)
D. The disturbance not better explained by another preexisting, established or evolving neurocognitive
disorder and do not occur in the context of a severely reduced level of arousal, such as coma.
E. There is evidence from the history, , PE, and lab findings that the disturbance is a direct physiological
consequence of another medical condition, substance intoxication or withdrawal, or exposure to a
toxin, or is due to multiple etiologies.
DELIRIUM: CLINICAL FEATURES

Core features of Delirium:

1. altered consciousness
2. altered attention
3. impairment in other realms of cognitive function
4. relatively rapid onset (usually hours to days)
5. brief duration (usually days to weeks)
6. often marked, unpredictable fluctuations in severity and other clinical manifestations during
the course of the day,
DELIRIUM: CLINICAL FEATURES
Associated Clinical Features:
1. Disorganization of thought process
2. Perceptual disturbances
3. Psychomotor hypo/hyper activity
4. Disruption of sleep-wake cycle (fragmented sleep at night)
5. Mood alterations
6. Autonomic hyperactivity or instability
7. Myoclonic jerking
8. dysarthria
DELIRIUM: CLINICAL FEATURES
• The major neurotransmitter hypothesized to be involved in delirium is
acetylcholine (decreased acetylcholine activity)

• the major neuroanatomical area is the reticular formation. (attention and

arousal)

• major pathway implicated in delirium is the dorsal tegmental pathway

DELIRIUM: CLINICAL FEATURES
• One of the most common causes of delirium is toxicity from too many prescribed
medications with anticholinergic activity.

• delirium associated with alcohol withdrawal has been associated with hyperactivity
of the locus ceruleus and its noradrenergic neurons

• Other neurotransmitters: serotonin and glutamate

• beclouded dementia – when delirium occurs in a patient with dementia

• sundowning – worsening of clinical manifestations at night

DELIRIUM: CLINICAL FEATURES
Bedside diagnosis; char. By sudden onset of symptoms

Mini-Mental Status Examination

EEG – generalized slowing of activity; focal areas of hyperactivity

Physical examination often reveals clues to the cause of the delirium.

 Bradycardia – Hypothyroidism, Stokes-Adams syndrome, Increased intracranial pressure 
 Tachycardia – Hyperthyroidism, Infection, Heart failure
 Fever – Sepsis, Thyroid storm, Vasculitis
DELIRIUM: CLINICAL FEATURES
DELIRIUM: DIFFERENTIAL DIAGNOSIS

1. Dementia
2. Schizophrenia –hallucinations and delusions are more constant and better
organized; no change in level of consciousness or orientation;
3. Depression – distinguished on basis of EEG
4. Dissociative Disorders
5. Factitious Disorders- inconsistencies in MSE and on basis of EEG
DELIRIUM: DIFFERENTIAL DIAGNOSIS
DELIRIUM: TREATMENT
I. TREAT THE UNDERLYING CAUSE
 Anticholinergic toxicity – Physostigmine salicylate (Antilirium) 1-2 mg IV or IM with repeated q 15 – 30
minutes

II. PROVIDE PHYSICAL, SENSORY AND ENVIRONMENTAL SUPPORT

 To prevent accidents
 Neither sensory deprived or overstimulated (black patch delirium)
 Regular sitter;friend or relative in the room
 Familiar pictures and decorations
 Clock orcalendar
 Regular orientations
DELIRIUM: TREATMENT
III. PHARMACOTHERAPY
 PSYCHOSIS : Haloperidol initial dose 2- 6 mg IM repeated in an hour if patient remains
agitated. Oral medication, the dose approx..1.5x the IM dose (liquid or tablet) twice daily,
with 2/3 of the dose given at bedtime.
 Droperidol – alternative IV formulation
 Phenothiazines should be avoided because of significant anticholinergic activity

 INSOMNIA : best treated with short- or intermediate-acting BDZ

 If with severe pain or dyspnea : should not hesitate to prescribe opioids

DEMENTIA
Major neurocognitive disorder

A disease process marked by progressive cognitive impairment in a

clear consciousness.

Dementia of Alzheimer’s is the most common type

Second most common in Vascular Dementia

DEMENTIA : EPIDEMIOLOGY
• prevalence of moderate to severe dementia in different population groups:
– approximately 5% in the general population >65 years of age
– 20 – 40% in the general population >85 years of age
– 15 – 20% in outpatient general medical practices
– 50% in chronic care facilities.

• dementia of the Alzheimer's type : 50 – 60%

• vascular dementia :15 – 30 %
• mixed vascular and Alzheimer's dementia: 10 – 15%
DEMENTIA : ETIOLOGY
DEGENERATIVE DEMENTIAS TUMOR primary or metastatic
Alzheimers, frontotemporal, Parkinson’s disease, Lewy TRAUMATIC
body dementia, idiopathic cerebral ferrocalcinosis
Dementia pulingistica, posttraumatic dementia, SDH
(Fahr’s dse.), progressive supranuclear palsy

MISCELLANEOUS INFECTION
Prion dse., AIDS, syphilis
Huntington’s dse., Wilson’s dse., metachromatic
leukodystrophy, neuroacathocytosis CARDIAC, VASCULAR, ANOXIA
PSYCHIATRIC Infarction, Biswanger dse., hemodynamic insufficiency
Pseudodementia of depression, cognitive decline in late DEMYELINATING DSE
life schizophrenia Multiple sclerosis
PHYSIOLOGIC DRUGS AND TOXINS
Normal pressure hydrocephalus Alcohol, heavy metals, irradiation, anticholinergics
METABOLIC (pseudodementia), carbon monoxide

Vitamin deficiencies, endocrinopathies, chr. metab. dist.

DEMENTIA : ALZHEIMER’S TYPE
• Commonly diagnosed in the clinical setting after other causes of dementia has been
excluded

• Amyloid precursors are hallmark

• GENETIC FACTORS:
– 40% of patients have a family history of dementia of the Alzheimer’s type
– Concordance rate higher among monozygotic twins (43%) than dizygotic twins (8%)
– Autosomal dominant transmission; rare
– Gene for amyloid precursor protein : long arm of chromosome 21
DEMENTIA : ALZHEIMER’S TYPE
• NEUROPATHOLOGY:
– GROSS: diffuse atrophy with flattened sulci and enlarged cerebral ventricles
– MICRO:
1. senile plaques – amyloid plaques* ; more strongly indicate Alzheimers dse.
2. neurofibrillary tangles- cytoskeletal elements; primarily phosphorylated tau protein; not
unique to Alzheimers dementia
3. neuronal loss (particularly in cortex and hippocampus)
4. synaptic loss (as much as 50% in the cortex)
5. granulovascular degeneration of the neurons
DEMENTIA : ALZHEIMER’S TYPE
• NEUROTRANSMITTERS:

– Hypoactivity of Acetylcholine and norepinephrine

– Specific degeneration of cholinergic neurons in nucleus basalis of Meynert
– Decreased acetylcholine and choline acetyltransferase concentrations in the brain
– Decrease NE containing neurons in the locus ceruleus
– Decreased concentrations of somatostatin and corticotropin (neuroactive peptides)
DEMENTIA : VASCULAR DEMENTIA

• Formerly multi-infarct dementia

• Primary cause presumed to be multiple areas of cerebral vascular disease
• Most commonly seen in men, esp. with preexisting hypertension
• Infarction of small and medium-sized cerebral vessels; multiple parenchymal
lesions spread over wide areas of the brain
• P.E.: carotid bruits, fundoscopic abnormalities, enlarged cardiac chambers
• BISWANGER’S DSE: subcortical arteriosclerotic encephalopathy
– Presence of many small infarctions of the while matter that spare the cortical regions
DEMENTIA : PICK’S DISEASE

• Frontotemporal dementia
• Neuronal loss, gliosis, and neuronal Pick’s bodies(cytoskeletal elements)
• Cause is unknown; approx. 5% of irreversible dementias
• Most common in men, with first degree relatives with the disorder
• Early stages are more often characterized by personality and behavioral
changes, with relative preservation of other cognitive functions
• Features of Kluver-Bucy syndrome more common
DEMENTIA : HUNTINGTON’S DSE.

• Subcortical type; more motor abnormalities and fewer language abnormalities

• Psychomotor slowing and difficulty with complex tasks, but memory, language
and insight remain intact in the early and middle stages
• Classic choreoathetoid movements
• High incidence of depression and psychosis
DEMENTIA : PARKINSON’S DSE.

• Subcortical type
• 20-30% of patients with Parkinson’s dse have dementia
• Bradyphrenia: slow movements paralleled in slow thinking
DEMENTIA : HIV-RELATED

• AIDS dementia complex or HIV dementia

• Annual rate of 14%
• Development of dementia often paralleled by the appearance of parenchymal
abnormalities in MRI scans.
• Other infectious dementias are caused by Cryptococcus or Treponema pallidum
• Personality changes: apathy, emotional lability or behavioral disinhibition.
DEMENTIA : HEAD TRAUMA-RELATED

• Dementia pugilistica – punch-drunk syndrome; occurs in boxers

• Emotional lability, dysarthria, and impulsivity
• Repeated concussion also seen in football players
DEMENTIA :
DSM V DIAGNOSTIC CRITERIA

A. Evidence of significant cognitive decline from a previous level of

performance in one or more cognitive domains based on:
1. Concern of the individual, a knowledgeable informant, or the clinician that there has
been a significant decline in cognitive function; and
2. A substantial impairment in cognitive performance, preferably documented by
standardized neuropsychological testing or another quantified clinical assessment.
B. The cognitive deficits interfere with independence in everyday activities
C. The cognitive deficits do not occur exclusively in the context of a delirium.
D. The cognitive deficits are not better explained by another mental disorder.
DEMENTIA : CLINICAL FEATURES

• Memory impairment is typically an early and prominent feature; early in the course it
is mild and usually most marked for recent events.
• As it progresses, memory impairment becomes severe, and only the earliest learned
information is retained
• Orientation progressively affected
• Language abilities esp in cortical dementias
• Changes in personality
• Hallucination and delusion
• Depression and anxiety
• Aphasia, apraxia, agnosia, seizures, primitive reflexes, sleep disturbances
DEMENTIA : CLINICAL FEATURES

• ACCORDING TO KURT GOLDSTEIN:

– Reduced ability to apply “abstract attitude”
• Generalizing from a single instance, forming concepts, grasping similarities and
differences
– Catastrophic reaction : agitation secondary to the subjective awareness of
intellectual deficits under stressful circumstances
• Patient attempts to compensate by using strategies to avoid demonstrating failures:
change subject, make jokes, divert the interviewer.
• Coarse language, inappropriate jokes, neglect of personal appearance and hygiene,
general disregard for the conventional rules of social conduct.
DEMENTIA : CLINICAL FEATURES

• SUNDOWNER SYNDROME:

– Characterized by drowsiness, confusion, ataxia, and accidental falls.

– Occurs in older people who are overly sedated and in patients with dementia wo
react adversely to even a small dose of a psychoactive drug;
– Also occurs in demented patients when external stimuli, such as light and
interpersonal orienting cues, are diminished.
DEMENTIA : DIFFERENTIAL DIAGNOSIS

1. Dementia of Alzheimer’s type vs Vascular dementia

– Decremental deterioration that can accompany CVD over time; focal neurological
symptoms are more common in vascular dementia
2. Vascular Dementia vs Transient Ischemic Attack
– TIAs are brief periods of focal neurological dysfunctions lasting <24 hours
3. Delirium
– Rapid onset, brief duration, cognitive impairment fluctuation during course of the day,
nocturnal exacerbation of symptoms, marked disturbance in sleep-wake cycle, and
prominent disturbances in attention and perception
DEMENTIA : DIFFERENTIAL DIAGNOSIS

1. Depression
– Depression-related cognitive dysfunction (pseudodementia)
2. Factitious disorder
– Erratic and inconsistent
3. Schizophrenia
– Less severe symptoms
4. Normal Aging
– Benign senescent forgetfulness; minor severity and no significant interference with social and
occupational behaviors
5. Other disorders: Malingering, Intellectual disability, amnestic disorder
DEMENTIA : DIFFERENTIAL DIAGNOSIS
DEMENTIA : DIFFERENTIAL DIAGNOSIS
DEMENTIA : DIFFERENTIAL DIAGNOSIS
DEMENTIA : DIFFERENTIAL DIAGNOSIS
DEMENTIA : TREATMENT

I. The first step in the treatment of dementia is verification of the diagnosis

 Preventive measures : changes in diet, exercise, and control of diabetes and
hypertension
 General treatment approach:
1. to provide supportive medical care
2. emotional support for the patients and their families
3. pharmacological treatment for specific symptoms, including disruptive behavior.
DEMENTIA : TREATMENT
II. PHARMACOTHERAPY
• benzodiazepines for insomnia and anxiety, antidepressants for depression, and antipsychotic drugs for
delusions and hallucinations
• should be aware of possible idiosyncratic drug effects in older people
• drugs with high anticholinergic activity should be avoided.

• CHOLINESTERASE INHIBITORS
– Donepezil (Aricept)
– Rivastigmine (Exelon)
– Galantamine (Remiryl)
– Tacrine (Cognex)

 MEMANTINE –acts on glutamate receptors

AMNESTIC DISORDERS
defined primarily by impairment in the ability to create new memories.

Amnesia is most commonly found in alcohol use disorders and in head injury

Major neuroanatomical structures :

dorsomedial and midline nuclei of the thalamus
Hippocampus
The mamillary bodies
the amygdala
AMNESTIC DISORDERS
The benzodiazepines are the most commonly used prescription drugs associated
with amnesia.

Thiamine deficiency, hypoglycemia, hypoxia (including carbon monoxide

poisoning), and herpes simplex encephalitis ;

anterograde amnesia - impairment in the ability to learn new information

retrograde amnesia - inability to recall previously remembered knowledge

Short-term and recent memory are usually impaired

AMNESTIC DISORDERS
Korsakoff's syndrome is an amnestic syndrome caused by thiamine deficiency

alcoholic blackout -conscious awareness of being unable to remember a period the

night before during which they were intoxicated.

Electroconvulsive therapy (ECT) treatments are usually associated with retrograde

amnesia for a period of several minutes before the treatment and anterograde amnesia
after the treatment.

Transient global amnesia - is characterized by the abrupt loss of the ability to recall
recent events or to remember new information.
last from 6 to 24 hours
AMNESTIC DISORDERS
The primary approach to treating amnestic disorders is to treat the underlying
cause.
1st phase of recovery - clinicians serve as a supportive auxiliary ego who
explains to a patient what is happening and provides missing ego functions
2nd phase of recovery- build a therapeutic alliance with patients by
explaining slowly and clearly what happened and by offering an explanation
for a patient's internal experience.
3rd phase of recovery - integrative
- help the patient form a new identity by connecting current experiences of
the self with past experiences
-Grieving over the lost faculties may be an important feature
MILD COGNITIVE IMPAIRMENT
1. Memory complaint, preferably qualified by an informant’
2. Memory impairment for age and education
3. Preserved general cognitive function
4. Intact activities of daily living
5. Not demented