TABLE 3.

The effect of statins dose intensification on cognitive function.

Dose-dependent effects on cognitive function	Protective	A meta-analysis showed that a 5-mg increase in the daily dose of statins was correlated with an 11% decrease in dementia risk (Zhang et al., 2018).
		A cohort study showed higher protective effects for a high dose (the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730) of statin than for a lower dose (Chang et al., 2019).
		A randomized controlled trial on older adults with hypertension showed that long-term use of 10 mg rosuvastatin may reduce WMH progression and cognitive impairment (Zhang et al., 2019).*
	Harmful	HIST (atorvastatin 40–80 mg, rosuvastatin 20–40 mg) was associated with a higher frequency of cognitive impairment compared to MIST (atorvastatin 10–20 mg, rosuvastatin 10 mg, simvastatin 20–40 mg, and pravastatin 40–80 mg) (Roy et al., 2020).
Dose independent effects on cognitive function	Protective	The statins use was negatively associated with all-cause dementia and vascular dementia in older adults regardless of statins dosage (10–80 mg per day) and LDL-C level (Zingel et al., 2021).
	No harmful	Statin switching from low-dose simvastatin (≤20 mg/day) to high-dose atorvastatin (40 mg/day) did not significantly worsen cognitive function, in patients with T2D (Thongtang et al., 2020).

*A synergistic interaction is reported between telmisartan and low-dose rosuvastatin, as an effective management strategy for the development and progression of WMH and cognitive impairment (Zhang et al., 2019). HIST, high-intensity statin therapy; LDL-C, low-density lipoprotein cholesterol; MIST, moderate-intensity statin therapy; T2D, type 2 diabetes.