Background:Despite the strong evidence of aerobic exercise as a disease-modifying treatment for Alzheimer’s disease(AD)in animal models,its effects on cognition are inconsistent in human studies.A major contributor to these findings is inter-individual differences in the responses to aerobic exercise,which was well documented in the general population but not in those with AD.The purpose of this study was to examine inter-individual differences in aerobic fitness and cognitive responses to a 6-month aerobic exercise intervention in community-dwelling older adults with mild-to-moderate dementia due to AD.Methods:This study was a secondary analysis of the Effects of Aerobic Exercise for Treating Alzheimer’s Disease(FIT-AD)trial data.Aerobic fitness was measured by the shuttle walk test(SWT),the 6-min walk test(6MWT),and the maximal oxygen consumption(V02max)test,and cog-nition by the AD Assessment Scale-Cognition(ADAS-Cog).Inter-individual differences were calculated as the differences in the standard devia-tion of 6-month change(SDR)in the SWT,6MWT,V02max,and ADAS-Cog between the intervention and control groups.Results:Seventy-eight participants were included in this study(77.4 ± 6.3 years old,mean ± SD;15.7 ± 2.8 years of education;41％were female).VO2max was available for 26 participants(77.7 ± 7.1 years old;14.8 ± 2.6 years of education;35％were female).The SDR was 37.0,121.1,1.7,and 2.3 for SWT,6MWT,V02max,and ADAS-Cog,respectively.Conclusion:There are true inter-individual differences in aerobic fitness and cognitive responses to aerobic exercise in older adults with mild-to-moderate dementia due to AD.These inter-individual differences likely underline the inconsistent cognitive benefits in human studies.