CH-15-Neurocognitive Disorders – Comprehensive Study Notes

Perspectives on Neurocognitive Disorders

• “Neurocognitive Disorders” (NCDs) ≈ DSM-5 umbrella term that replaced “Organic Mental Disorders” (early DSMs) and “Cognitive Disorders” (DSM-IV)
  • Shifts focus from etiology ("organic") to chief clinical feature: decline in cognitive functioning
  • Divided into three core groupings
  • Delirium (acute, fluctuating, usually reversible)
  • Major NCD (formerly “dementia”): substantial decline, interferes w/ independence
  • Mild NCD (new in DSM-5): modest decline, independence preserved with effort/compensation → early identification window
• Distinguish from neurodevelopmental conditions (e.g., intellectual disability, specific learning disorder) that manifest from birth/childhood
• Rapid advances in neurobiology have increased optimism: neurogenesis in aging brains, imaging biomarkers, disease-modifying pharmacology in pipeline
• Clinical relevance to psychology
  • Profound personality/behavior changes → depression, anxiety, paranoia, aggression
  • Family systems impact, caregiver burden, elder-abuse risk
  • Ethical issues in research (e.g., informed consent in delirious pts; distress in fMRI scanners)

Delirium

• Definition: Acute disturbance in attention & awareness, developing over hours–days, fluctuating during day, plus additional cognitive disturbance (memory, language, perception)
  • DSM-5 criteria summarised:
  • A. Disturbed attention/awareness
  • B. Acute/fluctuating onset
  • C. Additional cognitive disturbance
  • D. Not better explained by pre-existing NCD/coma
  • E. Physiological consequence of medical condition, substance, toxin, or multiple etiologies
• Prevalence & Epidemiology
  • \approx 20\% of older adults in ERs; high in postop, oncology, ICU, AIDS
  • ≥50\% of persons w/ dementia experience at least one delirium episode
  • Hospital delirium doubles (\times 2–4) 1-year mortality in critical-care samples
• Etiological Categories (DSM-5 subtypes)
  • Substance-intoxication / withdrawal (e.g., alcohol, benzos, “bath salts”, Ecstasy)
  • Medication-induced (high risk in elders due to polypharmacy & slowed clearance)
  • Medical condition (infection, metabolic, head injury, hypoxia, etc.)
  • Multiple etiologies / unspecified
• Example: Mr. J.—72-y/o male, new antihypertensive → substance-induced delirium; resolved 48 h after discontinuation
• Neurobiology
  • fMRI: lasting connectivity loss DLPFC–PCC; reversible thalamus–RAS disconnect
• Treatment
  • 1º: Treat underlying cause (infection, drug, electrolytes) ± haloperidol/olanzapine for agitation
  • Psychosocial: re-orientation cues, family presence, familiar objects, sleep hygiene
• Prevention
  • Multicomponent Hospital Elder Life Program (HELP): orientation, sensory aids, sleep, ambulation, hydration/nutrition, minimize psychoactive meds → high efficacy but resource-intensive
  • Managed care + drug counselling ↓ medication-related delirium

Major & Mild Neurocognitive Disorders

• Major NCD
  • Significant decline (≥2 SD on testing) in one+ domains; interferes with independent living
• Mild NCD
  • Modest decline (1–2 SD); independence intact with compensations (lists, alarms)
  • Adds formal DSM status to “Mild Cognitive Impairment (MCI)” research construct → early-intervention debate
• Core cognitive domains: complex attention, executive function, learning & memory, language, perceptual-motor, social cognition
• DSM-5 requires specifier due to etiological condition (Alzheimer’s, vascular, TBI, etc.)

Global Epidemiology

• \approx 5 \text{ million} Americans w/ Major NCD (all causes)
• Prevalence >5\% age >65; 20–40\% age >85
• One new dementia case worldwide every 7 seconds
• Mild NCD prevalence \approx 10\% ≥70 y (Einstein Aging Study)
  • Higher in Black elders vs White (11.6 % vs 8 %)

Neurocognitive Disorder due to Alzheimer’s Disease (AD)

• First described 1907 by Alois Alzheimer (51-y female patient)
• DSM-5 diagnostic highlights:
  • Insidious onset, gradual progression
  • Probable AD if (a) proven genetic mutation or (b) clear amnestic + one other domain decline, steady worsening, no mixed etiology
• Clinical picture
  • Early: recent-memory loss, disorientation, reduced interests (visuospatial deficits lead to wandering)
  • Cognitive signs: aphasia, apraxia, agnosia, impaired exec functions; “sundowning” agitation evenings
  • Psychiatric/behavioral: depression, delusions, aggression, apathy
• Disease course
  • Slow-fast-slow pattern; mean survival 4–8 y (range up to >20)
• Epidemiology
  • ~50\% of all Major NCDs; \approx 5.3 \text{ million} US cases
  • Rare <$45 y; prevalence doubles every 5 y after 75: \text{Incidence} \propto 2^{(\text{Age}-75)/5}
  • Predicted tripling by 2050 (baby-boom cohort)
• Risk / Protective Factors
  • Genetics: deterministic genes (APP 21, PSEN-1 14, PSEN-2 1) → early-onset; susceptibility gene apo E4 19 for late-onset; two alleles → ~90\% risk, ↓ age of onset (~84 \rightarrow 68 y)
  • Gene-environment examples: apo E4 × hypertension ↑ amyloid load; apo E4 × stress ↑ decline; exercise lowers risk only in non-E4 carriers
  • Education / Cognitive Reserve: higher education delays symptom onset yet faster decline once threshold crossed (reserve exhaustion). Hypothesis: more synapses → need more neuronal loss before clinical threshold.
  • Possible gender effect: higher prevalence in women ⇒ estrogen loss? WHIMS trial showed combined estrogen-progestin increased, not decreased, AD risk.
  • Cultural: prevalence comparable across ethnicities after adjusting for education & case-ascertainment; slightly lower in some Native American groups
• Neuropathology
  • Neurofibrillary tangles (hyper-phosphorylated tau) inside neurons
  • Amyloid plaques (β-amyloid peptide) extracellularly ⇒ neuronal death & cerebral atrophy; imaging ligands + CSF β-amyloid biomarkers now allow ante-mortem detection (ADNI project)
• Illustrative case: Pat Summitt – legendary basketball coach; early-onset AD dx at 57; memoir emphasises coping, advocacy, cognitive reserve via grit

Treatments for AD

• Symptomatic (current FDA-approved)
  • Cholinesterase inhibitors: donepezil, rivastigmine, galantamine → modest 6-month cognitive gain
  • NMDA antagonist: memantine (for mod-severe)
• Disease-modifying (investigational)
  • Anti-amyloid monoclonal antibodies & vaccines; β-secretase inhibitors
  • Stem-cell & neurotrophic factors (e.g., GDNF) experimental
• Adjunctive
  • SSRIs for depression/anxiety; low-dose antipsychotics for agitation (monitor strokes)
  • High-dose vitamin E showed mixed results; mega-dose risk ↑ mortality ⇒ not recommended
  • Exercise programs improve ADLs, cognition, mood
• Psychosocial/Environmental
  • Cognitive stimulation therapy (CST), reminiscence groups, computer brain-fitness apps
  • External memory aids: labelled cupboards, colour-coded maps, “memory wallets”, tablets with talking photo albums
  • Behavioral strategies for wandering, in-home monitoring (ethics: privacy vs safety)
  • Caregiver education: communication skills, assertiveness (Table 15.4), stress-management; internet-based modules (e.g., REACH II) emerging

Vascular Neurocognitive Disorder (VaD)

• Etiology: cerebral vascular disease (infarcts, ischemia, hemorrhage); abrupt-stepwise decline
• Core deficits: slowed processing & frontal-executive problems > memory
• Prevalence: 1.5\% (70-75 y) rising to 15\% (>80 y); higher in men (CV risk)
• Management focuses on prevention of strokes: control \text{BP}, \text{lipids}, \text{AFib}; antiplatelets; rehab for residual deficits

Other Specific NCD Etiologies

Biological, Psychological & Social Contributors

• Biological: genetics, vascular risk, infections, head trauma, neurotransmitter deficits
• Psychological: substance use, lifestyle (diet, exercise), educational attainment (cognitive reserve)
• Social/Cultural: access to care, stigma, caregiving norms, occupational safety; ritual cannibalism → prion NCD (kuru)
• Gene–Environment interactions central (apo E4 × HTN, stress, diet, exercise)

Caregiver Burden & Mental Health

• >60\% of caregivers meet criteria for anxiety; 37\% for depression
• High psychotropic use; 3\times general-population stress symptoms
• Caregiving itself may ↑ caregiver’s future NCD risk (chronic stress, inflammation)

Prevention Strategies (All-Cause NCD)

• Manage cardiovascular risk: keep systolic < 120 mmHg, treat AFib, control diabetes, stop smoking
• Physical activity ≥150 min moderate/week; social & intellectual engagement
• Mediterranean diet, adequate \text{B}{12} & \text{B}9 (folate)
• Head-injury prevention: helmets, fall-proof homes, sport protocols
• Public health programs (HELP for delirium; stroke awareness “FAST”)

Formulas & Statistics Quick-Sheet

• Doubling of dementia incidence every 5 years after 75 ⇒ I(age)=I_{75}\times2^{(age-75)/5}
• HELP components = {\text{orientation}, \text{senses}, \text{sleep}, \text{mobility}, \text{hydration}, \text{therapeutic activities}, \text{\small ↓psychoactive}}
• Apo E allele frequency & risk: \Pr(AD|E4/E4)\approx90\%; mean onset 68 y vs 84 y for non-E4
• Mini-Mental State Exam (MMSE) max = 30; Major NCD often <24

Ethical / Practical Considerations

• Informed consent in cognitively impaired research participants; proxy consent; minimal risk threshold
• Privacy vs safety in GPS/home monitoring tech
• Equity of access to advanced diagnostics & emerging disease-modifying drugs

Take-Home Connections

• NCDs illustrate biopsychosocial model: biological degeneration + psychological coping + social context determine trajectory.
• Early detection (mild NCD) + lifestyle modification provides window to compress morbidity—shortening period of severe impairment (Figure 15.2).
• Caregiver wellbeing is inseparable from patient outcomes—parallel interventions essential.
• Future breakthroughs likely from convergence of genetics, imaging, immunotherapy, and digital health.