Neurobiological mechanisms linking vitamin d signaling to cognitive decline and neurodegeneration: Untangling epidemiology, pathophysiology, and evidence

Table 1 Studies showing the relationship between vitamin D and cognitive function

Ref.	Population	Intervention (dose and duration)	Outcome (primary)	Key insight
Kang et al[47]	Generally healthy older adults (n = 3424)	2000 IU/day (2.8 years)	No benefit (no change in global cognition)	Intervention may be too late in “healthy” adults to prevent decline. Limited benefit when supplementation is initiated late in life in populations without severe baseline deficiency
Pham et al[48]	Community-dwelling older adults (n ≈ 21000)	60000 IU/month (5 years)	No benefit (no difference in cognitive impairment)	Monthly “bolus” dosing might differ biologically from daily intake
Bischoff-Ferrari et al[49]	Active older adults (n = 2157)	2000 IU/day (3 years)	No benefit (no change in cognitive performance)	Participants had high baseline vitamin D (replete), limiting potential gain. this high-power study suggests limited benefit when supplementation is initiated late in life
Yang et al[50]	Mild cognitive impairment patients (n = 183)	800 IU/day (12 months)	Improved [full-scale IQ, information and block design (P < 0.001)]	Targeted intervention in the early stage of pathology shows potential advantage
Jia et al[51]	Alzheimer’s disease patients (n = 210)	800 IU/day (12 months)	Improved (total IQ, Aβ biomarkers)	Benefit observed in established disease, possibly via amyloid clearance
Chen et al[52]	Mixed populations (24 RCTs)	Various	Mixed (benefit only in vulnerable groups)	Supports the “targeted” hypothesis: Only those with deficiency/impairment benefit

RCT: Randomized controlled trial.