Delirium / Dementia / Eating disorders

Organic Mental Disorders / Neurocognitive Disorders

• New term in DSM5 and ICD11:
• Neurocognitive disorders.

• This is a correct name because these disorders involve:
1. neurological cause.
2. cognitive impairment.

• Three important neurocognitive disorders:
• Delirium:
• Impairment of both consciousness and cognition.
• Dementia:
• Consciousness is intact;
• only cognition is impaired.
• e.g., memory, language, and other cognitive domains.
• Amnestic disorder:
• Only memory is affected.

Delirium

• Most common organic mental disorder.

• Has an acute onset.
• Symptoms develop suddenly (hours or a few days).

• Course is fluctuating.
• Symptoms may be more pronounced in the morning,
• decrease in the afternoon, and
• increase at night.

Predisposing factors

• Elderly people.

• Chronic or severe medical illness.
• e.g., pneumonia, COPD.

• Surgical illness.
• e.g., bypass surgery, fractured femur, appendicectomy, road traffic accidents.
• Common in the postoperative period.

• Certain substances.
• Notably alcohol.
• Alcohol withdrawal can cause delirium tremens.

Diagnosis of Delirium

• Impairment of consciousness
• Consciousness:
• awareness of self and surroundings.
• Clinical mentions:
• clouding of consciousness
• altered sensorium
• confusion
• reduced orientation (disorientation to time, place, person).

• Cognitive impairment
• Memory is affected
• Immediate and remote memory may be intact.
• Language impairment
• Perceptual abnormalities:
• Illusions.
• Hallucinations,
• especially visual hallucinations (e.g., seeing snakes).

• Attention may be impaired.
• Reduced ability to focus, sustain, or shift attention.
• Questions may need to be repeated multiple times.

• Additional symptoms:
• Motor disturbances (reduced or increased).
• Sleep disturbances (insomnia or excessive sleeping).
• Emotional disturbances (e.g., appearing sad, very irritable).

Assessment of Delirium

• Diagnostic tool:
• Confusion Assessment Method (CAM).

• EEG (electroencephalogram) findings:



• Diffuse slowing of the background activity
• regardless of cause.
• Exception:
• Alcohol or sedative hypnotic withdrawal
• shows low voltage fast activity.
• Alcohol → we lose voltage → but do everything fast

Treatment of Delirium

• It is an emergency.

• Usually reversible if the underlying cause is treated.

• Antipsychotics:
• For symptoms like delusions, hallucinations, and agitation.

• Benzodiazepines:
• For symptoms like insomnia.
• DOC for delirium tremens → Chlordiazepoxide

Dementia

• Definition:
• Progressive cognitive impairment in clear consciousness.

Symptoms (Cognitive Impairments)

• Mnemonic: MEMORY LAPSE.
• Memory impairment
• Amnesia
• Language impairment
• Aphasia
• Difficulty speaking,
• finding words,
• grammatical errors.
• Attention impairment
• complex attention
• e.g., difficulty focusing on multiple stimuli.
• Perceptual motor impairment.
• Apraxia: problem with fine movements (buttoning clothes, tying shoelaces).
• Agnosia: difficulty identifying objects or faces.
• Social cognition impairment.
• e.g., difficulty recognizing emotions, appearing cold.
• Executive function impairment (planning, organizing).
• Difficulty in performing activities of daily living.

Behavioural and Psychological Symptoms (Psychiatric symptoms)

• May also be present along with cognitive impairment:
• Personality changes.
• Delusions, hallucinations.
• Agitation, aggression.
• Sadness, depression, anxiety symptoms.

Most Common Types of Dementia (Overall)

• Most common:
• Alzheimer's disease (70-80%).

• Second most common:
• Lewy body dementia (15-35%).

• Third most common:
• Vascular dementia (5-20%).

Onset of Dementia

• Usually has an onset in elderly age.

• Early onset dementia:
• Onset before 65 years of age.

Classifications of Dementia

Reversible vs. Irreversible Dementia

• Most are progressive and irreversible.

• 10-15% of cases are reversible if the cause is treated.

Important Reversible Causes:

• Neurosurgical conditions:
1. Subdural haemorrhage (SDH).
2. Brain tumour, brain abscess.
3. Normal Pressure Hydrocephalus (NPH)

• Infections:
• Encephalitis, meningitis.

• Metabolic causes:
• Vitamin B12 deficiency (very important).
• Folate, Niacin, Thiamine deficiency.

• Endocrinal abnormality:
• Hypothyroidism (important).
• Hyperthyroidism, Hypo- and Hyperparathyroidism.

• Drugs/Toxins:
• Alcohol can cause reversible dementia.

Cortical vs. Subcortical Dementia

• (Based on the area affected first)

Feature	Cortical Dementia	Subcortical Dementia	Mixed
Site of brain	• Outer cortex	• Subcortical gray matter	Both
Symptoms	• Memory	• Motor	ㅤ
Language	• Aphasia present, • Dysarthria absent	• Aphasia absent, • Dysarthria present	ㅤ
Calculation	• Acalculia (+)	• Acalculia (-)	ㅤ
Coordination	• Preserved	• Bowed or Extended	ㅤ
Posture	• Upright	• Bowed or Extended	ㅤ
Examples	• Alzheimer's disease, • Pick's disease	• Parkinson (most common) • Huntington's disease • Westphal variant of HD • Progressive supranuclear gaze palsy • HIV D • Multiple Sclerosis • Wilson's disease	Vascular, Lewy body dementia
Mnemonic	Pick Alzheimers	Park and Hunt Multiple Wilson	Va lewy

• SNc → Substantia Nigra

• Norepinephrine locked in ICU → Locus ceruleus

• ↑↑ Dopamine activity → Madly (Schizophrenia) hunting ()

• ↓↓ GABA → ↓↓ inhibitions → during anxiety () and hunting ()

• Norad → patients becomes anxious ()

• ↓↓ AcH → Alzheimer's, Huntintons (↑↑ in Park)

Condition	NT	Location
Alzheimer's disease	↓↓ Acetyl choline	Nucleus basalis of Meynert
Parkinson's disease	Dopamine ↓↓ ↳ bradykinesia ↑↑ Acetyl choline	Nigrostriatal Mnemonic: Mayil (Meynert) Basil (Basalis) nu Achingum (Acetylcholine) Alzheimersum vannu
Addiction	Dopamine	Nucleus accumbens Mesolimbic Location ↳ Medial Frontal area ↳ Ventral tegmental area
ALS	Glutamate Amy → Glue	Hippocampus, Subthalamic nucleus → Memory A-delta fibres → Fast pain
Huntington's chorea	Dopamine ↑↑ GABA ↓↓ AcH ↓↓	Loss of GABA in striatum
Tetanospasmin ↳ spastic paralysis ↳ Presynaptic	GABA	Inhibits release of GABA
Strychnine ↳ spastic paralysis ↳ Postsynaptic	Glycine Stry → Gly	Inhibits release of glycine.
Mesocortical	ㅤ	Prefrontal cortex ↳ Motivation ↳ Emotional regulation ↳ Decision making ↳ Memory
Tuberoinfundibular	Dopamine	• Hypothalamus • Physiologic inhibition of prolactin

Parkinson's Disease

• Reason: Decrease in dopaminergic neurons.

Gross Finding: 

• Substantia nigra appears pale 
  (normally brown due to melanin, which decreases with dopamine).

Microscopic Finding: 

• Presence of Lewy bodies.
• Description: Round bodies, darker in center, whiter at periphery.
• Composition: Made of alpha-synuclein.
• Park (Parkinson's) is synonymous (Synuclein) with lawn (Lewy bodies

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A. DOPAMINERGIC DRUGS	ㅤ
1. Levodopa	• Peripheral DOPA decarboxylase • converts L-dopa to Dopamine Combination with • Carbidopa • Benserazide • ↓ Peripheral DOPA Decarboxylase inhibitors
↳ Levodopa induced Dyskinesia	• when levels are high • Rx: Amantidine
↳ On off phenomenon	• due to ↓ dose of Syndopa • Rx ↳ Selegeline (MAO B⛔) > (addl neuroprotective) ↳ Entecapone (COMT ⛔)
2. Amantadine	• MOA: Releases DA from vesicle. • NMDA Antagonist • Only anti Parkinsonian drug to treat dyskinesia • Nammada (NMDA) Thadiyan (amantidine) → avante kaalil neeranu (ankle edema), avante Liver um poi (Livido)
3. Metabolism Inhibitors	Selective MAO-B Inhibitors: • Selegiline • Rasagiline • Maavu (MAO) vach Rasavada (Rasagiline) undakki sell (selegiline) cheyyan COMT Inhibitors: • Entacapone • Tolcapone NOT USED → Hepatotoxicity • Comet (COMT) → vann ente (entacapone) Tholil (Tolcapone) irunna Capil veenu
4. Dopamine Agonists	• Directly works on dopamine receptors • Pramipexole • Ropinirole • S/E: Pathological gambling • Parkinsonism (DOC) • Restless leg syndrome (DOC: Pregabalin/Gabapentin) • Premikkunnavare (pramiprexole) tie with rope (repinirole) → dopamine effect (agonist)
5. Istradefylline	• Adenosine [A2A] receptor antagonist
6. Deep Brain stimulation	• Subthalamic nucleus > Globus Pallidus interna
B. ANTI-CHOLINERGIC DRUGS	ㅤ
1. Central Anti-cholinergics:	• Benzhexol [Trihexyphenidyl] • DOC: For Drug Induced Parkinsonism. • Try Benz with 6 wheels → Trihexyphenidyl
2. First Generation Anti-histaminic drugs:	• Promethazine

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Lewy Body Disease (Dementia due to Lewy bodies)

• Second most common overall cause of dementia.

• Subcortex > cortex

Three core features:

1. Fluctuating cognitive impairment (variations in attention/alertness)

2. Visual hallucinations.

3. Motor features of parkinsonism (tremors, rigidity, bradykinesia)

Suggestive features:

• REM sleep behavior disorder.

• Severe neuroleptic sensitivity.

Supportive features:

• Repetitive falls, syncope, transient loss of consciousness.

• Severe autonomic dysfunction.

• Systematized delusions
• e.g., delusion of persecution
• Capgras syndrome.

• Other delusions or hallucinations (auditory, tactile).

Microscopic findings:

• Lewy bodies
• eosinophilic inclusions of alpha-synuclein
• Also found in Parkinsons and MSA
• Lewy Parkin Shy

Differential diagnosis with Parkinson's disease dementia:

• Parkinson's disease dementia:
• Motor symptoms develop first.
• Cognitive symptoms follow (at least 1 year later).
• It is a subcortical dementia.

• Lewy body disease:
• Cognitive symptoms present from the beginning.
• Motor symptoms may be present initially or occur later.

Assessment of Dementia

• Tool: Mini Mental State Examination (MMSE).

• A screening tool for cognitive symptoms.

• Score < 24 out of 30 is suggestive of dementia.

• Developed by Folstein et al.

Progressive Supranuclear Gaze Palsy

 

• Mnemonic: Square frame wave cheythu → Humming bird ullil kude mukalilot parannu poi

• Seen in Atypical Parkinsonism.
• unresponsive to levodopa

• Tauopathy

• a type of Parkinson's plus syndrome.

• Presentation:
• A patient with Parkinsonian features unresponsive to levodopa
• Patient has rigidity or bradykinesia.
• Vertical gaze palsy.
• Difficulty in looking downwards.
• Recurrent falls in backward direction.

• NOTE: In typical parkinsonism:
• Person walks slowly.
• Will not be able to lift foot over obstacle.
• Might hit against stone/brick.
• Topple over and fall forwards.

• EOG:
• Square wave jerks.
• NOTE: Square root wave sign:
• Constrictive pericarditis

• Brain area involved:
• Basal ganglia and superior colliculus.

• MRI head:
• Hummingbird appearance.
• Midbrain atrophy with bulging pons.

• Biopsy:
• Substantia nigra and locus ceruleus show
• neuronal loss,
• ballooned neurons
• tangles.

• No drug of choice for management.

• Poor prognosis.

Multisystem Atrophy (MSA) / shy dragger

• Parkinson's plus syndromes
• α synuclein accumulate in Oligodendrocyte

• Autonomic symptoms (Erectile dysfunction) ++
• recurrent urinary infections

• cerebellar signs

• "bent-over" posture
• (stooped posture observed in idiopathic PD)

• Types
• MSA P → Parkinsonian → Putaminal ring
• MSA C → Cerebellar → Hot cross bun sign

• Lewy Parkin Shy

• Cross cut Bun with a dagger

Corticobasal degeneration

• Alien limb phenomenen

• Parkinson's plus syndromes

Alzheimer's Disease (AD)

• Most common type of dementia.

• Cortical dementia.

• Seen in senile old age (after 70 years).

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Structure	Braak Staging	Example Symptom
Entorhinal Cortex	I–II (earliest)	Forgetting recent events (e.g., breakfast)
Hippocampus	III–IV (next)	Cannot recall recent conversation
Nucleus Basalis	Early–mid, with cortical spread	Poor attention

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Mnemonic: Ente Hippum base um

• Gradual and insidious onset.

• Temporal → Parietal → Frontal

• Slightly more common in females.

• Most common presentation:
• memory deficit.
• Language disturbance and other domains (agnosia, apraxia) affected gradually.

• Genetic Factors:

Genetic Factor	Chr.	Associated Effect
Amyloid Precursor Protein (APP)	21	• Premature Alzheimer's by 30 years in Down Syndrome • due to increased APP • APP → Premature
Presenilin 1 (PS1)	14	ㅤ
Presenilin 2 (PS2)	1	ㅤ
APOE E4 mutations	19	• Results in late onset Alzheimer's • Bad Prognosis • APO E → Early • 4 bad people
Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)	6	• late onset Alzheimer's
APO E2	ㅤ	• Good Prognosis • too (2) good

• Mnemonic (PS): 
• PlayStationil (PS → Presenilin) Game (gamma secretase activity) → from 14 years old (chromosome 14)
• At 21 → Alzheimers () vannu → aappilaayi (APP)

• Diagnosis: 4A
• Amnesia
• Apraxia
• Agnosia
• Aphasia
• → Apraxia/Aphasia:
• Parietal and temporal lobe involvement

Clock face test:

• Hemineglect

• Finds cognition defect > Apraxia

Microscopic Findings:

Feature	Description
Amyloid Plaques	• A beta amyloid in center • neurites at periphery • (senile/neuritic plaques)
Neurofibrillary Tangles (NFTs)	• Flame-shaped hyperphosphorylated tau proteins. • Bielschowsky stain in brain • (Tau): Tau protein to Taoji as Alzheimer's occurs at Taoji's age (70-75).
Hirona Bodies	• Needle-shaped Actin • (Hirano): Hirano (Hero) is always made for acting.
Cerebral Amyloid Angiopathy (CAA)	• Blood vessel deposition of amyloid
Granulovacuolar Degeneration	• Presence of vacuoles in the brain

Neurotransmitters implicated:

• Acetylcholine is reduced.

• Glutamate is increased (can cause excitatory damage).

Screening test:

• MMSE (mini-mental state examination)
• MMSE <24/30 suggestive of Dementia
• MMSE may be false positive in depression

Investigation of choice:

• Functional MRI
• Detects hypometabolism in parietal & temporal lobe

Treatment:

Condition	Rx
Mild	Donepezil
Severe	Memantine (NMDA)
Mabs	Lecanemab, Aducanumab Alzheimer patient says “Lei can (Lecanemab) still Adukaam (Aducanumab) → Do None (Donenumab) ”
Transdermal patch	Rivastigmine (Ach ⛔)

• Cholinesterase Inhibitors:
• Mechanism: Increase acetylcholine levels.
• Drugs: Donepezil, Rivastigmine, Galantamine.
• Rivastigmine and Donepezil
• transdermal patch
• Tacrine not used much (hepatotoxicity).
• Can cause severe GI side effects.

• Memantine:
• Mechanism:
• Non-competitive NMDA antagonist
• decreases glutamate levels
• Used in moderate to severe Alzheimer's disease.
• Can be used as monotherapy or with Donepezil.

• Monoclonal Antibodies for Alzheimer's Disease
• Mechanism:
• Human IgG1 monoclonal antibodies that clear A beta deposits.
• Given as IV infusion.
• Approved for mild cognitive impairment or mild dementia stage of AD.
• Mnemonic (AL D):
• Alzheimer patient says
  “Le i can (Lecanemab) still Adukaam (Aducanumab) → Do None (Donenumab) ”
• Aducanumab.
• Lecanemab (Approved 2023).
• Side effects:
• headache,
• infusion reactions,
• ARIA (Amyloid Related Imaging Abnormalities).
• Donanemab (Approved July 2024).

Normal Pressure Hydrocephalus (NPH):

• Wet-Wacky-Wobbly Grandpa

• Presents with Hakim's triad (Adam's triad):
1. Cognitive impairment.
2. Gait abnormality (magnetic gait).
• Shuffling gait with preserved arm swing
3. Urinary incontinence.

• Treated by shunting.

HIV associated Neurocognitive disorder (HAND)

• HIV + Subcortical dysfunction

• Microglial nodule + Giant cell

Vascular Dementia / Multi-infarct Dementia

• Occurs due to vascular events (stroke).

• Characterized by a step-ladder pattern of symptoms.
• Stepwise deterioration corresponding to new strokes.

• More common in males.

Frontotemporal Dementia (Pick's Disease)

• Picks dementia → loss of inhibitions → Pick a knife → put in Frontal lobe

• Characterized by:
• atrophy of frontal and temporal lobes.
• Pick bodies are seen.

• It is a cortical dementia.

• Second most common cause of early onset dementia.

Two variants:

• Behavioral variant (frontal lobe affected):
• Disinhibitory behavior (e.g., public urination).
• Apathy, lack of concern.
• Stereotypic movements, hyperorality.
• Personality changes,
• emotional disturbances.

• Language variant (temporal lobe affected):
• Language impairment.

Treatment of Dementia

• First step:
• treat the cause,
• especially if reversible.

Treatment of Behavioural and Psychological Symptoms in Dementia

• Antidepressants (e.g., SSRIs):
• For depression and anxiety.

• Antipsychotics (e.g., Risperidone, Olanzapine):
• For agitation, delusions, hallucinations.
• Clozapine:
• low EPS
• For psychosis in Parkinson's and Lewy body dementia

• Pimavanserin:
• Inverse agonist at 5HT2A.
• Approved for psychosis in Parkinson's disease.

• Brexpiprazole:
• Partial D2 agonist.
• Approved for agitation associated with dementia due to Alzheimer's disease.

• Benzodiazepines:
• For agitation and insomnia.

Amnestic Disorder

• There is only memory impairment (amnesia).

Symptoms

• anterograde amnesia
• Mainly recent memory is impaired.

• retrograde amnesia may be present.

• Reduced ability to recall past events

Intact functions

• Immediate memory

• Consciousness intact
• distinguishes from delirium

• Global intellectual damage
• distinguishes from dementia

Causes

• CNS causes:
• Seizures, head trauma, infections, tumours.

• Important systemic cause:
• Thiamine deficiency.
• Alcohol-induced amnestic disorder is known as Korsakoff syndrome.
• Caused by thiamine deficiency.

Sleep-Wake Disorders

Eating Disorders

• TOC: CBT + Nutritional rehabilitation

Prevalence

• Binge eating disorder > Anorexia nervosa > Bulimia nervosa
• Anorexia nervosa lifetime prevalence: 2 to 4%.
• Bulimia nervosa lifetime prevalence: 2%.

Anorexia Nervosa

• "Anorexia" is a misnomer;
• patient does not have a loss of appetite.

• More common in females (ratio 10:1).

• Onset: 14 to 18 years (young adolescent females).

Clinical features:

• ↓ Weight
• Adults:
• BMI < 18.5 kg/m² (ICD-11).
• Children/Adolescents:
• BMI for age under fifth percentile.

• Intense fear of weight gain or fatness.

• Disturbance of body image (perceives self as fat).

• Amenorrhea is no longer a necessary criterion.

• Delayed sexual development.

• Decreased interest in sexual activities.

Subtypes:

• Restricting type:
• Most common subtype (50% of cases).
• Restricts food intake and may do excessive exercise.

• Binge eating purging subtype:
• Binge eating:
• Large food intake in less duration.
• Purging:
• Compensatory mechanisms.
• Self-induced vomiting, use of laxatives, diuretics, emetics.
• Sometimes, excessive exercise.

Course and prognosis:

• High mortality rate (one of the highest in psychiatry).

• Death due to medical complications of low weight and malnutrition.

Treatment:

• Difficult as patients
• often secretive,
• deny symptoms,
• resist treatment.

• Hospitalization may be required:
• To restore nutritional status.
• To manage complications (dehydration, electrolyte imbalance).
• If patients are 20% below their normal weight for height.

• In hospitalization:
• Primary goal:
• Nutritional rehabilitation and weight restoration.
• Calories
• started low (1500-1800 kcal/day),
• then increased.
• Refeeding syndrome:
• Main cause of death:
• Congestive heart failure
• Arrhythmias
• Metabolic derangements:
• ↓ PO4+ (main driver).
• ↓K+, ↓Ca2+, ↓Mg2+.
• Mnemonic: PAPPM
• Fluid overload.
• Patient at risk:
• BMI <16 kg/m3 .
• Unintentional weight loss >15% within last 3-6 months (≥1 factor).
• Little/no nutrition intake for >10 days.
• ↓K+, ↓PO4+, ↓Mg+ prior to feeding.
• If no weight gain,
• monitor 2 hours after each meal
• for self-induced vomiting.

• Behavioural management (therapy) is used.

• SSRIs may also be beneficial.

Bulimia Nervosa

• "Bulimia" means ox hunger.

• More common in females (ratio 10:1).

• Onset: Late adolescence or young adulthood.

Clinical features:

• Episodes of binge eating.

• Inappropriate compensatory behavior
• Purging: Self-induced vomiting, laxatives, diuretics, emetics.
• Non-purging: Excessive exercise, fasting.

• Occurs at least once per week for 3 months for diagnosis.

• Fear of gaining weight or desire to lose weight.

Key difference from Anorexia Nervosa:

• Weight is normal or may be increased.

• Note: These are also seen in Anorexia (binge-purging type); differentiate by weight/BMI.

Complications of purging:

• Enamel erosion, dental caries.

• Parotitis (swelling of parotid gland).

• Russell sign: Callus on knuckles.

• Electrolyte imbalances:
• hypokalemia, hypochloremia, hyponatremia.
• Alkalosis.

Treatment:

• Can be treated on an OPD (outpatient department) basis.

• Patients are usually not secretive and accept treatment.

• First-line therapy:
• Cognitive Behavior Therapy (CBT).

• Drugs: SSRIs (e.g., Fluoxetine).

Binge Eating Disorder

• A new entity in DSM-5.

• More common in females (ratio 1.75:1).

Clinical feature:

• Episodes of only binge eating.
• Not followed by any compensatory behavior.

• Sense of lack of self-control.

• Patient's weight may be overweight or in the obese range.

• May lead to complications associated with obesity.

Treatment of Binge Eating Disorder

• First-line: Cognitive Behavior Therapy (CBT).

• SSRIs have shown some results.

• Lisdexamfetamine is FDA approved for short-term treatment.
• Decreases weight and binge episodes.

• Mnemonic: Lisa kk 10 amphetamine kodukkum → binge eat cheyyan