The　cognitive　reserve　(CR)　hypothesis　is　reinforced　by　negative　moderating　effects,　suggesting　that　those　with　higher　CR　are　less　reliant　on　brain　structure　for　cognitive　function.　Previous　research　on　CR＇s　moderating　effects　yielded　inconsistent　results,　motivating　our　3　studies　using　UK　Biobank　data.　Study　I　examined　five　CR　proxies＇　moderating　effects　on　global,　lobar,　and　regional　brain-cognition　models;　study　II　extended　study　I　by　using　a　larger　sample　size;　and　study　III　investigated　age-related　moderating　effects　on　the　hippocampal　regions.　In　study　I,　most　moderating　effects　were　negative　and　none　survived　the　multiple　comparison　correction,　but　study　II　identified　13　global-level　models　with　significant　negative　moderating　effects　that　survived　correction.　Study　III　showed　age　influenced　CR　proxies’　moderating　effects　in　hippocampal　regions.　Our　findings　suggest　that　the　effects　of　CR　proxies　on　brain　integrity　and　cognition　varied　depending　on　the　proxy　used,　brain　integrity　indicators,　cognitive　domain,　and　age　group.　This　study　offers　significant　insights　regarding　the　importance　of　CR　for　brain　integrity　and　cognitive　outcomes.　©　2023　Elsevier　Inc.