Polyunsaturated fatty acids, including omega-3 (Eicosapentanoic acid (EPA), Docosahexaenoic acid (DHA), Docosapentanoic acid (DPA)[1], and omega-6 (alpha-linolenic acid (ALA), Linoleic acid (LA), arachidonic acid (AA))[2] are known to play a crucial role in protecting against neurodegeneration and functional decline associated with ageing. However, available targeted studies have predominantly evaluated interventions exceeding two years, while the effects of short-term treatment during the early stages of memory impairment remain largely unexplored. This study focuses on exploring the association between change in levels of blood biomarkers (omega-3 and omega-6 fatty acids) from baseline to 6 months and cognitive domains, physical function at 6 months in a cohort of community-dwellers who are at risk of developing dementia. In the present secondary longitudinal analysis, 147 participants having subjective memory impairment (SMI) were pooled from the PONDER study, a randomized control trial conducted in 60-85 years old community-dwellers which were allocated to intervention (5 g omega-3 powder, vitamin D3 1000 IU and 25g whey protein concentrate 80) along 2X weekly supervised resistance exercise program, or placebo with stretching and flexibility session for 6 months period. Blood biomarkers were assessed using the Lepage and Roy method, and APOE genotype was identified using PCR (Polymerase Chain Reaction). Cognitive domains were assessed using Cogstate Computerized Battery, and physical function was assessed by 30s sit-to-stand test (STS), 4-metre walk Test (FMWT) and Timed-up-go Test (TUG). Multiple regression analysis examined the association between the change in Biomarker levels (from baseline to 6 months) and Cognitive domains and Physical function, after 6 months. To understand the association better, five models were constructed. Higher DHA concentrations at six months were associated with better executive function (β = 0.158, p = 0.048). Longitudinal increases in DPA (β = 0.150, p = 0.035) and AA (β = 0.180, p = 0.027) were associated with improved executive function. Increased gait speed (FMWT) was associated with elevated levels of EPA (β = 0.216, p = 0.044), DHA (β = 0.242, p = 0.003) and DPA (β = 0.213, p = 0.01), and higher DPA was associated with improved TUG performance (β = 0.200, p = 0.038) over 6-month period. APOE ε4 status did not significantly modify the observed associations. Thus, findings of this study indicate that elevated levels of n-3 and n-6 PUFA are positively associated with cognitive domains as well as physical function outcomes in individuals with subjective memory impairment over the 6-month period from baseline. These findings highlight the potential role of n-3 and n-6 PUFAs in supporting brain and physical health. However, the role of the APOE ε4 allele in the mechanisms underlying the association between n-3 PUFA levels and physical health outcomes remains to be further explored.