Table 1.

Comparison of classical AD and ARCD based on clinical course and risk factors. When examining the background and clinical course of classical AD and ARD, it becomes clear that they describe entirely different disease processes that should be considered separately. PSEN—presenilin. APP—Amyloid precursor protein.

	Early-Onset (Classical) Alzheimer’s Disease	Age-Related Dementia
Age of onset	30–60 years	>60 years
Genetics	Monogenic/familial: PSEN1, PSEN2, APP. ~40–50% of mutations are sporadic.	Polygenic. Most significant risk gene (ApoE) contributes ~5% of total risk and is variably penetrant based on context and environment.
Clinical course	Homogeneous	Heterogeneous
Effect of environment	Minimal, or poorly described.	Substantial. Education, diet, exercise, cardiovascular and metabolic health, history of trauma, sleep, stress, pollutants, smoking, and alcohol all have a documented role.
Prevalence	~1% of all AD cases and decreasing (previously estimated to represent 5% of all AD) [23].	~10% of individuals >65 and increasing (projected to double by 2050) [24]. ~99% of all AD cases [23].