Study guide
14.5 Delirium & the Pharmacotherapy of Cognitive Disorders
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan
2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia
4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)
3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV
5 Chapter 4: Infectious Disease (9% of Exam)
4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections
6 Chapter 5: Pulmonary Disease (9% of Exam)
5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule
7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
9 Chapter 8: Medical Oncology (6% of Exam)
8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care
10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
11 Chapter 10: Neurology (4% of Exam)
10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders
12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)
11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health
13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)
13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings
16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity
19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
14.5 Delirium & the Pharmacotherapy of Cognitive Disorders
Key Takeaways Explain This Topic AI
Delirium in the elderly is a named Geriatric Syndromes subsection and medical causes of delirium appear under Neurology.
Delirium is defined by acute onset, fluctuating course, inattention and altered level of consciousness.
Hypoactive delirium is more common than hyperactive delirium in older adults and is frequently missed.
Multicomponent non-pharmacologic prevention reduces incident delirium, whereas prophylactic antipsychotics do not.
Antipsychotics are reserved for severe agitation threatening safety and do not shorten delirium duration.
Last updated: August 2026
- Pharmacotherapy of Alzheimer Disease & Anti-Amyloid Monoclonal Antibodies
- 1. Acetylcholinesterase Inhibitors (AChEIs)
Agents: Donepezil (5-10 mg PO daily; up to 23 mg daily), Rivastigmine (1.5-6 mg PO BID or 4.6-13.3 mg/24h transdermal patch), Galantamine (8-24 mg PO daily extended-release).
Mechanism: Reversibly inhibits acetylcholinesterase, increasing synaptic acetylcholine concentration in the central nervous system.
Adverse Effects (Cholinergic Excess): Gastrointestinal (nausea, vomiting, diarrhea, anorexia, weight loss), central (vivid dreams, insomnia), and cardiovascular ( bradycardia, sick sinus syndrome, AV block, and syncope ). Baseline ECG should be checked prior to initiation in patients with suspected conduction disease.
2. NMDA Receptor Antagonists
Agent: Memantine (5-20 mg PO daily; titrate weekly by 5 mg).
Mechanism: Uncompetitive, low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist. Blocks pathological tonic glutamate excitotoxicity without interfering with physiological neurotransmission.
Indication: Moderate-to-severe AD (MMSE <20) either as monotherapy or combined with Donepezil (demonstrates additive functional and cognitive benefits).
Adverse Effects: Dizziness, headache, confusion, and constipation.
3. Amyloid-Beta Directed Monoclonal Antibodies (Lecanemab & Donanemab)
Lecanemab (Leqembi - approved 2023): Humanized IgG1 mAb targeting soluble amyloid-beta protofibrils (10 mg/kg IV every 2 weeks).
Donanemab (Kisunla - approved 2024): Humanized IgG1 mAb targeting insoluble, N-terminally truncated pyroglutamate amyloid-beta plaques (administered IV every 4 weeks).
Clinical Indications: Indicated strictly for Early Symptomatic AD (patients with Mild Cognitive Impairment due to AD or Mild AD Dementia ) with objective, laboratory-confirmed brain amyloid pathology (via Amyloid Positron Emission Tomography [PET] or CSF biomarker ratios [ A β 42 / A β 40 A\beta_{42}/A\beta_{40} A β 42 / A β 40 and phosphorylated tau p-tau 181 \text{p-tau}_{181} p-tau 181 ]).
Mandatory Pre-Treatment Genotyping: Baseline Apolipoprotein E (ApoE) genotyping is mandatory. Homozygous ApoE ε 4 / ε 4 \varepsilon4/\varepsilon4 ε 4/ ε 4 carriers have the highest risk of developing severe, life-threatening amyloid-related adverse events.
Amyloid-Related Imaging Abnormalities (ARIA) & MRI Surveillance:
ARIA-E (Vasogenic Edema): Sulcal effusion and parenchymal vasogenic edema on FLAIR sequences. Occurs in 12-25% of patients (highest in ApoE4 homozygotes). Often asymptomatic, but can manifest as headache, confusion, visual disturbances, dizziness, or seizures. Requires temporary drug suspension until edema fully resolves on follow-up MRI.
ARIA-H (Microhemorrhages & Superficial Siderosis): Intracerebral petechial microbleeds and leptomeningeal hemosiderin deposition on gradient-echo (GRE) or susceptibility-weighted imaging (SWI) MRI. If >4 new microhemorrhages or superficial siderosis develop, therapy must be held or discontinued permanently.
Surveillance Protocol: Baseline brain MRI within 12 months, followed by routine surveillance MRIs prior to the 5th, 7th, and 14th infusions (for Lecanemab) or weeks 12, 24, and 52 (for Donanemab).
1. Delirium: Diagnosis, Etiologies & Management
Delirium is an acute, fluctuating disturbance in attention, awareness, and baseline cognition. It occurs in up to 30-50% of hospitalized older adults and carries a 1-year mortality of 35-40%.
Clinical Subtypes
Hyperactive Delirium (25%): Agitation, psychomotor restlessness, delusions, vivid hallucinations, paranoia, and combative behavior. Readily recognized.
Hypoactive Delirium (50%): Lethargy, psychomotor slowing, apathy, decreased verbal output, and stupor. Most common subtype and frequently missed (often misdiagnosed as depression or worsening dementia; carries worse clinical outcomes).
Mixed Delirium (25%): Fluctuates between hyperactive and hypoactive states.
Confusion Assessment Method (CAM) Diagnostic Algorithm
Diagnosis of delirium requires the presence of Feature 1 AND Feature 2 PLUS EITHER Feature 3 OR Feature 4 :
Feature 1: Acute Onset and Fluctuating Course (Evidence of acute change in mental status from baseline; behavior waxes and wanes over the course of a day).
Feature 2: Inattention (Difficulty focusing, sustaining, or shifting attention; assessed by asking patient to spell "WORLD" backwards, recite months of the year backwards from December, or perform serial 7 subtractions).
Feature 3: Disorganized Thinking (Rambling, irrelevant, or incoherent conversation; illogical flow of ideas; unpredictable switching between subjects).
Feature 4: Altered Level of Consciousness (Any state other than "alert", including hyperalert/vigilant, lethargic, stuporous, or unarousable).
Etiologies: The DELIRIUMS Mnemonic
D — Drugs: Anticholinergics, sedative-hypnotics, opioids, corticosteroids, polypharmacy, drug intoxication.
E — Electrolyte Disturbances / Endocrine: Hyponatremia, hypercalcemia, hypoglycemia, thyroid storm/myxedema, acute adrenal insufficiency.
L — Lack of Drugs (Withdrawal): Alcohol withdrawal (delirium tremens), benzodiazepine withdrawal, SSRI discontinuation.
I — Infection: Urinary tract infection (UTI), pneumonia, sepsis, bacteremia, meningitis, encephalitis, COVID-19, C. diff colitis.
R — Reduced Sensory Input: Uncorrected visual or hearing impairment, sleep deprivation, social isolation.
I — Intracranial Disorders: Acute ischemic stroke, intracranial hemorrhage, subdural hematoma, non-convulsive status epilepticus, traumatic brain injury.
U — Urinary Retention & Fecal Impaction: Bladder outlet obstruction, severe constipation/obstipation (extremely common occult triggers).
M — Myocardial / Metabolic / Hypoxia: Acute coronary syndrome, acute decompensated heart failure, pulmonary embolism, hypoxemia, hypercapnia, hepatic encephalopathy, uremic encephalopathy.
S — Surgery / Severe Pain / Sleep Deprivation: Postoperative state, general anesthesia, uncontrolled acute pain.
Evidence-Based Management of Delirium
First-Line: Environmental & Non-Pharmacologic Interventions (The HELP Protocol):
Frequent Reorientation: Clocks, calendars, clear communication, whiteboards with nurse/date names, familiar personal photos.
Sensory Optimization: Ensure patient is wearing functioning eyeglasses and hearing aids.
Circadian Sleep-Wake Cycle: Bright natural sunlight during daytime; quiet, dim environment at night; eliminate non-essential nighttime vitals, medication passes, and phlebotomy between 22:00 and 06:00.
Early Mobilization: Ambulate out of bed >=3 times daily; physical and occupational therapy.
Remove Tethering Devices: Prompt removal of urinary Foley catheters, sequential compression devices when ambulating, and unnecessary IV lines.
AVOID Physical Restraints: Physical restraints drastically increase agitation, delirium duration, falls, strangulation, and mortality. They are strictly contraindicated.
Pharmacologic Management: Highly Restricted Indications:
ABIM Board Rule: Antipsychotics are NOT recommended for the prevention of delirium, nor for the treatment of hypoactive delirium or mild agitation .
Emergency Rescue Pharmacotherapy: Reserved ONLY for patients with severe, intractable agitation or perceptual disturbances that pose an immediate, life-threatening danger to patient/staff safety or interrupt critical medical therapies (e.g., pulling out endotracheal tubes, central venous lines).
Medication Regimens: Low-dose Haloperidol (0.5 to 1.0 mg PO/IV) or atypical antipsychotics ( Quetiapine 12.5-25 mg PO, Olanzapine 2.5-5 mg PO). Monitor QTc interval on ECG. Discontinue within 24-48 hours as soon as severe agitation resolves.
CRITICAL CONTRAINDICATION: Benzodiazepines (Lorazepam) are CONTRAINDICATED in delirium (they worsen and prolong delirium, increase paradoxical agitation, and cause respiratory depression). EXCEPTION: Benzodiazepines are first-line ONLY when delirium is caused by alcohol or sedative-hypnotic withdrawal .