Pathophysiology
Clinical meaning
Major neurocognitive disorder (dementia) is defined by the DSM-5 as significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) that interferes with independence in everyday activities. The diagnostic approach requires the NP to (1) establish that cognitive decline is present and significant, (2) determine if it interferes with functional independence, and (3) rule out reversible causes before concluding irreversible neurodegeneration. Reversible causes of cognitive decline account for approximately 9-15% of dementia presentations and must be systematically excluded. Hypothyroidism causes cognitive slowing, depression, and psychomotor retardation through reduced thyroid hormone effects on neuronal metabolism and myelination. Vitamin B12 deficiency impairs myelin synthesis and causes megaloblastic changes in the CNS, producing cognitive decline, peripheral neuropathy, and subacute combined degeneration of the spinal cord. Normal pressure hydrocephalus (NPH) presents with the classic triad of gait disturbance (magnetic gait), urinary incontinence, and dementia — caused by impaired CSF absorption leading to ventricular enlargement compressing periventricular white matter; it is potentially reversible with ventriculoperitoneal shunting. Depression (pseudodementia)...