Not all cognitive functions age the same way. Fluid intelligence (novel problem-solving, processing speed) peaks around 25 and declines gradually thereafter. Crystallized intelligence (accumulated knowledge, vocabulary) stays stable or grows until ~65-70 before a mild decline. Cognitive reserve (Stern, 2002) lets people with the same amyloid/tau pathology show very different functional outcomes.
Fluid(age) = 100 − 0.55·max(0, age−25) − P·40·(1 − 0.5·CR)
Cryst(age) = 100 + 0.15·min(age,65 )-25) − 0.35·max(0,age−65) − P·18·(1 − 0.5·CR)
Synapses(age)= 100 − 0.35·max(0,age−30) − P·45·(1 − 0.5·CR)
P = pathology load (0 in normal aging, rises with age in AD trajectory)
CR = cognitive reserve / 100 (buffers pathology's functional cost, not the pathology itself)
- Age — drives baseline synaptic pruning, white-matter loss and the natural fluid-intelligence decline visible in every brain.
- Cognitive reserve — does not reduce plaques or tangles, but buffers how much functional decline the same pathology causes (the Nun Study: high idea-density writing → far less dementia at equal autopsy-confirmed pathology).
- Alzheimer's trajectory — adds amyloid-β plaques (amber, growing with age past ~50) and hyperphosphorylated-tau-driven synaptic loss around them, with a ~15-20 year silent phase before symptoms appear.
- Neuroinflammation toggle — shows microglia (small reactive particles) clustering around active plaques, releasing IL-6/TNF-α that adds further synaptic toxicity.