Clinical meaning
Cognitive decline encompasses a spectrum from subjective cognitive complaints to mild cognitive impairment (MCI) to dementia. Alzheimer disease (most common) involves extracellular amyloid-beta plaque deposition, intracellular neurofibrillary tangles (hyperphosphorylated tau protein), synaptic loss, and cholinergic neuron degeneration in the hippocampus and association cortices. Vascular cognitive impairment results from chronic cerebrovascular disease (white matter lesions, lacunar infarcts). Lewy body dementia involves alpha-synuclein aggregates causing fluctuating cognition, visual hallucinations, and parkinsonism. Frontotemporal dementia involves tau or TDP-43 protein aggregates causing personality changes and language deficits. Reversible causes (vitamin B12 deficiency, hypothyroidism, normal pressure hydrocephalus, medication effects, depression) must be excluded before diagnosing neurodegenerative disease.
Diagnosis & workup
Diagnostics & workup: - Cognitive screening: MMSE (max 30; <24 suggests dementia), MoCA (max 30; <26 suggests MCI; more sensitive than MMSE for MCI), SLUMS, Mini-Cog (3-item recall + clock draw) - Distinguish MCI from dementia: MCI = cognitive impairment WITHOUT functional impairment in IADLs; dementia = cognitive impairment WITH functional decline - Laboratory workup to exclude reversible causes: TSH, B12, folate, CBC, CMP, RPR/VDRL, HIV (if risk factors), urinalysis - Brain MRI: hippocampal atrophy (Alzheimer), white matter changes (vascular), frontal/temporal atrophy (FTD); exclude structural lesions, NPH, subdural hematoma - CSF biomarkers (when diagnosis uncertain): low amyloid-beta42, elevated phospho-tau, elevated total tau (Alzheimer pattern) - Amyloid PET scan: detects amyloid plaques in vivo; appropriate when diagnosis uncertain and would change management - Neuropsychological testing: detailed domain-specific assessment (memory, language, executive function, visuospatial, attention)