3.6 Neurocognitive Disorders

Core Neurocognitive Domains (DSM-5-TR)

Neurocognitive disorders (NCDs) represent a decline from a previously attained level of cognitive functioning. Diagnosis requires systematic evaluation across six core cognitive domains defined by the DSM-5-TR:

1. Complex Attention: Sustained attention, divided attention, selective attention, and processing speed.
2. Executive Function: Planning, decision-making, working memory, responding to feedback, flexibility, and overriding habits (inhibition).
3. Learning and Memory: Immediate memory, recent memory (free recall, cued recall, recognition memory), and long-term/very long-term memory (semantic, autobiographical, implicit learning).
4. Language: Expressive language (naming, word finding, fluency, grammar) and receptive language (comprehension).
5. Perceptual-Motor: Visual perception, visuoconstructive reasoning, perceptual-motor coordination, and praxis (executing motor acts).
6. Social Cognition: Recognition of emotions, theory of mind (empathy, understanding others' mental states), and behavioral self-regulation.

Diagnostic Severity Thresholds

• Mild Neurocognitive Disorder: Substantial cognitive decline in one or more domains, but cognitive deficits do not interfere with capacity for independence in everyday activities (e.g., complex instrumental activities of daily living [IADLs] like managing finances or medications are preserved, though requiring greater effort or compensatory strategies).
• Major Neurocognitive Disorder (Dementia): Significant cognitive decline in one or more domains that interferes with independence in everyday activities (requiring assistance with IADLs or basic activities of daily living [ADLs]).

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Delirium: Clinical Syndrome & PMHNP Management

Delirium is a life-threatening medical emergency characterized by an acute disturbance in attention and awareness that fluctuates in severity over hours to days. It is a neuropsychiatric manifestation of underlying systemic physiological dysfunction.

DSM-5-TR Diagnostic Criteria

• Criterion A: A disturbance in attention (reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment).
• Criterion B: The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.
• Criterion C: An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception).
• Criterion D: The disturbances are 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.
• Criterion E: Evidence from the history, physical examination, or laboratory 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.

Clinical Subtypes

• Hyperactive: Characterized by psychomotor agitation, restlessness, hypervigilance, hallucinations, and emotional lability. Often recognized quickly.
• Hypoactive: Characterized by lethargy, sluggishness, psychomotor slowing, and apathy. Frequently misdiagnosed as depression or severe dementia, carrying a higher mortality rate due to delayed intervention.
• Mixed: Fluctuates rapidly between hyperactive and hypoactive states.

Etiology: The DELIRIUM Mnemonic

Diagnostic Evaluation Workup

1. Laboratory Panel: CBC, Comprehensive Metabolic Panel (CMP: electrolytes, BUN, creatinine, LFTs, calcium), Urinalysis and urine culture, Thyroid-stimulating hormone (TSH), Serum Vitamin B12 and Folate, Rapid Plasma Reagin (RPR) or VDRL, Blood alcohol and urine drug screen.
2. Physiological & Cardiac: Arterial Blood Gas (ABG), Electrocardiogram (ECG), Chest X-ray.
3. Neuroimaging & Specialized Tests: Non-contrast Brain CT or MRI (if focal neurological signs or head trauma), Lumbar Puncture (if meningitis/encephalitis suspected), Electroencephalogram (EEG) showing generalized diffuse background slowing (delirium) vs. focal spikes or normal alpha rhythm (pseudodementia/depression).

PMHNP Management & Intervention Protocols

• Primary Goal: Identify and treat the underlying medical cause immediately.
• Non-Pharmacological Measures (First-Line): Environmental reorientation (clocks, calendars, family presence), maintaining sleep-wake cycles (daylight exposure, quiet night environment), sensory aids (ensuring glasses and hearing aids are worn), early mobilization, hydration. Avoid physical restraints, which increase agitation and fall risk.
• Pharmacological Interventions (Reserved strictly for severe agitation/psychosis endangering patient or staff safety):
  • Haloperidol (Haldol): High-potency FGA, 0.5 mg to 2.0 mg PO/IM. Minimal anticholinergic effect. Monitor QTc interval on EKG.
  • Second-Generation Antipsychotics: Quetiapine (12.5–25 mg), Olanzapine (2.5–5 mg), or Risperidone (0.25–0.5 mg).
  • Contraindications: Avoid Benzodiazepines in delirium UNLESS the delirium is caused by alcohol or sedative-hypnotic withdrawal (Delirium Tremens), as benzodiazepines worsen delirium from other etiologies.

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Differential Diagnosis: Major Neurocognitive Disorders

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Subtype Profiles & PMHNP Prescribing Guidelines

1. Alzheimer's Disease (AD)

• Pathophysiology: Widespread loss of cholinergic neurons originating in the Nucleus Basalis of Meynert. Beta-amyloid plaques accumulate extracellularly, causing neuroinflammation, while intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein disrupt axonal transport.
• Genetics: Early-onset AD (<65 years, autosomal dominant): Mutations in APP (Chromosome 21), PSEN1 (Chromosome 14), and PSEN2 (Chromosome 1). Late-onset AD: Apolipoprotein E epsilon 4 (APOE-ε4) allele on Chromosome 19 increases risk.
• Pharmacological Management:
  • Cholinesterase Inhibitors (Mild to Severe AD): Donepezil (Aricept) (5–10 mg QD; up to 23 mg), Rivastigmine (Exelon) (oral or transdermal patch—ideal for dysphagia or GI intolerance), Galantamine (Razadyne). Common side effects: Nausea, vomiting, diarrhea, bradycardia, syncope, insomnia, vivid dreams.
  • NMDA Receptor Antagonist (Moderate to Severe AD): Memantine (Namenda) (5–20 mg QD). Blocks pathological tonic influx of glutamate into NMDA receptors, preventing excitotoxic neurotoxicity. Can be combined with Donepezil (Namzaric).
  • Disease-Modifying Biologics: Monoclonal antibodies targeting amyloid-beta (e.g., Lecanemab, Donanemab). Requires baseline MRI and monitoring for ARIA (Amyloid-Related Imaging Abnormalities): ARIA-E (edema/effusion) and ARIA-H (microhemorrhage/siderosis).

2. Vascular Neurocognitive Disorder

• Pathophysiology: Result of multi-infarct dementia, single strategic stroke, or subcortical ischemic vascular disease (small vessel disease affecting thalamocortical circuits).
• Clinical Presentation: Executive dysfunction (impaired planning, sequencing, processing speed) typically exceeds memory impairment in early stages. Step-wise decline is classic.
• PMHNP Management: Focus on secondary prevention of cerebrovascular events: antihypertensives, statins, diabetes management, smoking cessation, antiplatelet agents (Aspirin, Clopidogrel). Cholinesterase inhibitors are beneficial if mixed AD/Vascular etiology exists.

3. Dementia with Lewy Bodies (DLB) vs. Parkinson's Disease Dementia (PDD)

• The 1-Year Rule:
  • DLB: Cognitive decline and neurobehavioral symptoms occur before or simultaneously with (within 1 year of) parkinsonian motor signs.
  • PDD: Extrapyramidal motor signs (Parkinson's disease) are established for more than 1 year before the onset of neurocognitive decline.
• CRITICAL PMHNP WARNING — Antipsychotic Hypersensitivity: Up to 50% of DLB patients exhibit life-threatening reactions to antipsychotics (severe EPS, acute deterioration of rigidity, irreversible parkinsonism, somnolence, and precipitous NMS). First-line treatment for psychotic symptoms is Cholinesterase Inhibitors. If severe, distressing hallucinations persist, low-dose Quetiapine (12.5–50 mg), Clozapine, or Pimavanserin (Nuplazid) (selective 5-HT2A inverse agonist) should be used.

4. Frontotemporal Neurocognitive Disorder (FTD)

• Behavioral Variant (bvFTD): Early disinhibition (socially inappropriate behavior, loss of decorum), apathy, loss of sympathy/empathy, hyperorality (dietary changes, craving sweets, putting inedible objects in mouth), repetitive/compulsive behaviors.
• Language Variants (Primary Progressive Aphasia): Semantic variant (loss of word meaning/object identification) vs. Nonfluent/agrammatic variant (hesitant, effortful speech with grammatical errors).
• Prescribing Pearl: Cholinesterase inhibitors are ineffective and frequently exacerbate behavioral agitation, disinhibition, and GI upset. SSRIs (Sertraline, Trazodone) are preferred for disinhibition, compulsive behaviors, and mood symptoms.

5. Other Specific Etiologies

• Normal Pressure Hydrocephalus (NPH): Ventricular enlargement with normal CSF opening pressure. Symptom triad: Gait Disturbance (broad-based, slow, short-stepped, "magnetic" gait—feet glued to floor; usually the first symptom), Urinary Incontinence (urgency and frequency), and Dementia (psychomotor slowing, apathy). Treatment: Ventriculoperitoneal (VP) shunt placement.
• Creutzfeldt-Jakob Disease (CJD): Transmissible spongiform encephalopathy caused by prions. Presentation: Rapidly progressive dementia, startle-induced myoclonus, cerebellar ataxia. Diagnostic findings: Generalized periodic sharp wave complexes on EEG; elevated 14-3-3 protein or tau protein in CSF; hyperintensity in basal ganglia/cortex ("cortical ribboning") on diffusion-weighted MRI.
• HIV-Associated Neurocognitive Disorder (HAND): Subcortical pattern of impairment featuring psychomotor slowing, executive dysfunction, apathy, and motor clumsiness. Treatment: Optimization of combination Antiretroviral Therapy (cART) with high Central Nervous System Penetration Effectiveness (CPE) scores.