1. Normal Aging

Cognitive Changes: Mild decline in processing speed and difficulty with multitasking or word-finding (“tip of the tongue”). Memory lapses are occasional and do not disrupt daily life (e.g., misplacing keys).
Functional Impact: No interference with activities of daily living (ADLs) or instrumental ADLs (IADLs). Patient remains independent.
Key Differentiator: Subjective complaints without objective, significant decline on cognitive testing. Function is preserved.

2. Mild Neurocognitive Disorder (MCI)

Cognitive Changes: Evidence of modest cognitive decline in one or more domains (e.g., memory, executive function) that is noticeable to the patient, an informant, or the clinician. More persistent than normal aging.
Functional Impact: No significant interference with independence in IADLs, though tasks may take longer or require compensatory strategies.
Key Differentiator: Objective evidence of cognitive decline on testing, but independence in daily life is preserved. It represents a transitional state between normal aging and major neurocognitive disorder.

Cognitive Changes: Evidence of significant cognitive decline from a previous level in one or more domains. This is a general term, not a specific disease.
Functional Impact: Cognitive deficits interfere with independence in everyday activities (IADLs like managing finances/medications, and eventually basic ADLs).
Key Differentiator: Cognitive decline is severe enough to impair functional independence.

Clinical Presentation: Patient often has a history of depression and complains emphatically about memory loss (“I don’t know” answers). Onset is often subacute and can be dated precisely. Associated with classic depressive symptoms (anhedonia, sleep/appetite changes).
Cognitive Profile: Deficits are often related to poor effort and concentration. Patients appear distressed by their cognitive symptoms.
Key Differentiator: Cognitive symptoms improve with treatment of depression. Patients are more likely to self-report cognitive problems than those with dementia. However, late-life depression is a significant risk factor for developing true dementia later.

Patho/Etiology: Most common cause of dementia. Accumulation of extracellular amyloid-beta plaques and intracellular neurofibrillary tangles (hyperphosphorylated tau).
Clinical Presentation: Gradual, progressive decline. Early and prominent memory impairment (amnestic) is the classic feature, followed by language and visuospatial deficits. Behavioral changes often occur later.
Diagnosis: Clinical diagnosis. Brain imaging shows diffuse or temporal/parietal lobe atrophy. CSF may show low amyloid-beta 42 and high tau.

Patho/Etiology: Second most common cause. Caused by cerebrovascular disease (e.g., multiple infarcts, small vessel disease).
Clinical Presentation: Stepwise decline in function with periods of stability followed by sudden deterioration. Presentation depends on the location of infarcts; executive dysfunction is often more prominent than memory loss early on. Focal neurological deficits may be present.
Diagnosis: Clinical history supported by neuroimaging (MRI) showing evidence of strokes or significant white matter disease.

Patho/Etiology: Degeneration of the frontal and/or temporal lobes. Can be associated with tau protein (Pick bodies) or TDP-43 inclusions.
Clinical Presentation: Younger age of onset (typically 40s-60s) is a key clue.
- Behavioral variant (bvFTD): Early and prominent changes in personality, behavior, and social conduct (e.g., disinhibition, apathy, compulsive behavior).
- Primary Progressive Aphasia (PPA): Early and prominent language deficits (e.g., word-finding difficulty, impaired grammar).
Key Differentiator from AD: In early stages, memory and visuospatial skills are relatively preserved compared to the profound behavioral or language changes.