Dementia (Neurocognitive Disorder)

Definition

• Complex attention
• Executive function
• Learning and memory
• Language
• Perceptual-motor ability
• Social cognition
• Goldman-Cecil Medicine, p. 3861

Epidemiology

• 5-10% of people over age 65 have dementia; this rises to 30-50% of those over age 85
• Prevalence roughly doubles every 5 years after age 65
• Alzheimer disease (AD) accounts for 60-80% of all dementia
• Dementia reduces life expectancy by approximately half compared to non-demented individuals of the same age
• Textbook of Family Medicine 9e, p. 1339; Goldman-Cecil Medicine, p. 3862

Types and Their Key Features

• Goldman-Cecil Medicine, p. 3862; Guyton and Hall Textbook of Medical Physiology

Diagnosis

Step 1 - Establish the syndrome

• Delirium - impaired alertness (rules out dementia acutely)
• Depression (pseudodementia) - prominently affected mood/behavior; can mimic dementia; untreated depression independently raises long-term dementia risk
• Mild cognitive impairment (MCI) - impaired IADLs but ADLs intact; 2 SD below norm; significant risk of progression to dementia
• Normal aging (AAMI) - subjective memory concerns but normal on testing

Step 2 - Cognitive testing

• Mini-Cog or MMSE: adequate for moderate-to-severe dementia
• Neuropsychometric testing: required for mild impairment (bedside tests lack sensitivity at the mild end)
• Neurologic exam: look for focal signs (cerebrovascular), extrapyramidal features (Lewy body/Parkinson)

Step 3 - Laboratory workup (rule out reversible causes)

• Hypothyroidism/hyperthyroidism
• Vitamin B12 deficiency
• Chronic liver/renal failure
• Hypocalcemia/hypercalcemia
• HIV, cryptococcal/TB meningitis, tertiary syphilis
• Sedating drugs (opioids, sedatives, corticosteroids, digoxin)

Step 4 - Neuroimaging

Left: patient when cognitively normal. Right: same patient 11 years later, demented - dramatic hippocampal atrophy visible. (Goldman-Cecil Medicine, Fig. 371-3)

• Goldman-Cecil Medicine, p. 3861-3863

Pathophysiology of Alzheimer Disease (Most Common Type)

• Beta-amyloidosis begins accumulating in the neocortex up to 20 years before clinical dementia
• Soluble oligomeric forms of beta-amyloid are the likely key pathogenic molecules
• Neurofibrillary tangles (hyperphosphorylated tau) spread from medial temporal lobe → association cortices in a predictable pattern; tangle burden closely mirrors clinical severity
• The most consistent neurotransmitter deficit is cholinergic (nucleus basalis, septum, diagonal band), which is the target for pharmacotherapy
• Hippocampal atrophy is characteristic and measurable on MRI
• Goldman-Cecil Medicine, p. 3863-3864

Clinical Stages of Alzheimer Disease

• Short-term memory difficulty (forgetting names, recent events)
• Depression and apathy common

• Disorientation, confusion, impaired judgment
• IADLs then ADLs progressively impaired

• Difficulty speaking, swallowing
• Failure to recognize loved ones
• Bedridden, requiring total care

• Textbook of Family Medicine 9e, p. 1340

Management

Pharmacologic (Alzheimer Disease)

• Start AChEIs at low dose, titrate slowly
• Multiple formulations available (transdermal patch, ODT, liquid) to aid compliance
• All AChEIs appear equally efficacious
• Benefit documented at 52 weeks; benefit beyond that is uncertain
• Textbook of Family Medicine 9e, p. 1340; Goldman-Cecil Medicine, p. 3382

Non-Pharmacologic and General Principles

• Disclose the diagnosis early
• Caregiver education, training, and support groups
• Keep patient mentally active
• Assess functional status and safety (driving, financial management)
• Screen for behavioral/psychiatric symptoms (agitation, wandering)
• Advance care planning - ideally while patient retains capacity

End-Stage/Palliative Care

• PEG tube feeding is not recommended in advanced dementia - does not reduce aspiration, improve wound healing, or increase survival. Hand feeding and comfort feeding are preferred.
• Hospice enrollment improves symptom management and reduces unnecessary healthcare utilization
• Patients with dementia typically die of sepsis, pneumonia, pulmonary embolism, or heart disease - not directly from dementia
• Bradley and Daroff's Neurology in Clinical Practice; Goldman-Cecil Medicine

Prevention

• Vascular risk factor control (hypertension, diabetes, hyperlipidemia) may lower risk
• Low educational achievement is a consistent risk factor (reduced cognitive reserve)
• A 2025 meta-analysis in Age Ageing found an association between certain vaccinations and reduced dementia risk
• Head injury is a risk factor, primarily through chronic traumatic encephalopathy

Key Clinical Pearls

• Dementia = intact alertness + impaired cognition + functional impairment. If alertness is impaired, think delirium first.
• Always rule out reversible causes before concluding the dementia is degenerative.
• MCI is not dementia - IADLs may be impaired but ADLs are preserved. Close monitoring for progression is warranted.
• "Pseudodementia" (depression mimicking dementia) must be actively excluded; treat depression and reassess cognition.
• Mixed pathology is common at autopsy - pure syndromes are relatively less frequent.

Purulent (Bacterial) Meningitis

Definition

• Goldman-Cecil Medicine, p. 3997

Epidemiology

• Incidence in developed countries: 0.5-1.5 cases per 100,000 adults - dramatically reduced by vaccination
• Despite vaccine-related decline in incidence, mortality (~15%) has not changed
• Since the Haemophilus vaccine, S. pneumoniae now accounts for ~70% of cases and the disease predominantly affects older adults
• Worldwide, incidence is related to poverty and remains a major cause of morbidity and mortality
• Goldman-Cecil Medicine, p. 3999

Causative Organisms (Age-Based)

• Textbook of Family Medicine 9e, p. 1232; Rosen's Emergency Medicine

Pathophysiology

1. Nasopharyngeal colonization - bacteria colonize and invade the mucosa; capsular properties protect them from phagocytosis
2. Blood-brain barrier crossing - once in CSF, local host defenses (complement, immunoglobulins) are ineffective
3. Bacterial proliferation in CSF - triggers leukocyte recruitment
4. Inflammatory cascade - cytokine release into CSF promotes:
   • Increased blood-brain barrier permeability
   • Cerebral vasculitis
   • Cerebral edema
   • Raised intracranial pressure (ICP)
5. Reduced cerebral blood flow - leading to cerebral hypoxia and neuronal injury

• Rosen's Emergency Medicine, p. 2268

Clinical Features

1. Fever
2. Headache
3. Neck stiffness (nuchal rigidity)

• Nausea and vomiting (35%)
• Seizures (30%)
• Cranial nerve palsies, focal neurologic signs (10-20%)
• Meningismus (50%) - assessed by:
  • Kernig's sign: resistance to knee extension after hip and knee flexion
  • Brudzinski's sign: involuntary knee flexion in response to rapid neck flexion
• Photophobia, confusion, lethargy, sweats, rigors
• Petechial/purpuric rash starting as maculopapular on extremities - strongly suggests meningococcal meningitis
• Papilledema: <1% early; if present, consider brain abscess or mass

• Neonates: poor feeding, irritability, vomiting, temperature instability, apnea; nuchal rigidity unreliable; bulging fontanelle (late); seizures in 40%
• Elderly: insidious presentation, variable meningeal signs, altered mental status, possible absence of fever
• Textbook of Family Medicine 9e, p. 1232

Predisposing Factors

• Otitis media (most common)
• Sinusitis, mastoiditis
• Closed-head trauma with CSF leak
• Neurosurgery, penetrating trauma
• Immunocompromise, asplenia
• Alcoholism, burns
• Age extremes (neonate, elderly)

Diagnosis

When to do CT before LP

If CT is needed before LP, draw blood cultures and start antibiotics + dexamethasone immediately - do not delay treatment for imaging.

CSF Findings - Bacterial vs. Viral Meningitis

Other Diagnostic Tests

• Gram stain: first-line rapid test; sensitivity 60-90% in community-acquired cases
• Culture: gold standard; sensitivity reduced if antibiotics given first
• PCR: helpful when Gram stain is negative (especially for meningococcus)
• Blood cultures: always draw before antibiotics
• Serum CRP: helpful when Gram stain is equivocal
• Low-risk criteria (Bacterial Meningitis Score): negative Gram stain + CSF ANC <1,000 + CSF protein <80 mg/dL + peripheral ANC <10,000 cells/mL = very low risk for bacterial meningitis
• Textbook of Family Medicine 9e, p. 1232-1233; Adams and Victor's Principles of Neurology

Treatment

Empiric Antibiotic Therapy (by age/setting)

Pathogen-Directed Therapy

Adjunctive Dexamethasone

• Adults: 0.15 mg/kg IV every 6 hours x 2-4 days, given 10-20 minutes BEFORE (or at least concomitant with) the first dose of antibiotic
  • Strongly indicated for suspected/proven pneumococcal meningitis
  • Many experts give it to all adults since etiology is initially unknown
  • Do NOT give if antibiotics have already been started (no benefit)
  • Continue only if CSF shows gram-positive diplococci or cultures positive for S. pneumoniae
• Infants and children with Hib meningitis: 0.15 mg/kg q6h x 2-4 days, before first antibiotic dose
  • Beneficial for H. influenzae meningitis
  • Controversial for pneumococcal meningitis in children (insufficient evidence)
  • Not recommended for neonates (insufficient data)
• Textbook of Family Medicine 9e, p. 1234

Duration of Therapy

Prophylaxis

• Adults: 600 mg orally twice daily x 2 days
• Children >1 month: 10 mg/kg (max 600 mg) every 12 hours x 2 days
• Children <1 month: 5 mg/kg every 12 hours x 2 days
• Pregnant women: rifampin contraindicated; use ceftriaxone IM as single dose (125 mg if ≤15 years, 250 mg if >15 years)

• Textbook of Family Medicine 9e, p. 1235

Complications and Prognosis

Mortality

Neurologic Sequelae

• Sensorineural hearing loss: occurs early (within 1 day of onset); caused by suppurative cochlear destruction via the cochlear aqueduct
  • Pneumococcal: 31% persistent hearing loss
  • Meningococcal: 10.5%
  • H. influenzae: 6%
• Hydrocephalus: infrequent complication
• Cerebral venous/arterial thrombosis: almost one-third of adults with pneumococcal meningitis
• Seizures: up to 30% during illness; late seizures in some survivors
• Residual neurologic deficits (motor, cognitive, language): up to 30% with pneumococcal meningitis, 25% with H. influenzae
• Cranial nerve palsies (other than deafness) typically resolve over weeks to months
• Adams and Victor's Principles of Neurology, p. 717; Rosen's Emergency Medicine, p. 2268

Key Clinical Pearls

• Do not delay antibiotics waiting for CT or LP - draw blood cultures, then start vancomycin + 3rd-gen cephalosporin ± ampicillin immediately if there are indications for CT first
• Dexamethasone must be given before or with the first antibiotic dose to be effective - it is useless if given after
• A petechial/purpuric rash = meningococcemia until proven otherwise - a medical emergency
• Neonates and elderly may have atypical presentations without the classic triad
• Rifampin may reduce the efficacy of oral contraceptives - counsel contacts accordingly
• Pre-treatment with antibiotics reduces Gram stain and culture yield but does not significantly affect CSF cell counts or protein