Objectives:　Given　the　escalating　global　prevalence　of　age-related　cognitive　impairments,　identifying　modifiable　factors　is　crucial　for　developing　targeted　interventions.　Methods:　After　excluding　participants　with　dementia　and　substantial　missing　data,　453,950　individuals　from　UK　Biobank　(UKB)　were　included.　Cognitive　decline　was　assessed　across　four　cognitive　domains.　The　top　10%　exhibiting　the　greatest　decline　were　categorized　as　the　＂Cognitively　At-Risk　Population＂.　Eighty-three　potential　factors　from　three　categories　were　analyzed.　Univariate　and　multivariate　Cox　proportional　hazards　models　were　employed　to　assess　the　independent　and　joint　effects　of　these　factors　on　cognitive　decline.　Population　Attributable　Fractions　(PAFs)　were　calculated　to　estimate　the　potential　impact　of　eliminating　each　risk　category.　Results:　Our　findings　revealed　a　significant　impact　of　unfavorable　medical　and　psychiatric　histories　on　processing　speed　and　visual　episodic　memory　decline　(Hazard　Ratio　(HR)　=　1.34,　95%　CI:　1.20-1.51,　p　=　6.06　x　10(-)7;　HR　=　1.50,　95%　CI:　1.22-1.86,　p　=　1.62　x　10(-)4,　respectively).　Furthermore,　PAF　analysis　indicated　that　physiological　and　biochemical　markers　were　the　most　critical　risk　category　for　preventing　processing　speed　decline　(PAF　=　7.03%),　while　social　and　behavioral　factors　exerted　the　greatest　influence　on　preventing　visual　episodic　memory　decline　(PAF　=　9.68%).　Higher　education,　socioeconomic　status,　and　handgrip　strength　emerged　as　protective　factors,　whereas　high　body　mass　index　(BMI),　hypertension,　and　depression　were　detrimental.　Conclusions:　By　identifying　this　high-risk　group　and　quantifying　the　impact　of　modifiable　factors,　this　study　provides　valuable　insights　for　developing　targeted　interventions　to　delay　cognitive　decline　and　improve　public　health　outcomes　in　middle-aged　and　older　adults.