# The Link Between Physical Function, \(\beta\)-Amyloid, and Cognitive Aging in Women
## 4 Discussion
Concerning our work, the study sample was made up of exclusively women and, according to the results of a recently published study, both sexes experience a modified effect of PA on A\(\beta\) load [31]. Secondly, most studies have evaluated PA via questionnaires, and only a few have assessed PA via objective measures such as an accelerometer [32]. Although PA and FC are related, they are separate physiological and behavioral measures that can explain different aspects and predict various health outcomes. In this sense, our results are based on TUG performance as an objective measure of FC, which reflects individual fitness and is an early predictive factor of brain deterioration [10]. Consistent with the literature [30; 31], our regression model found that greater A\(\beta\) deposition at baseline and fewer years of education were associated with increased risk of cognitive impairment at baseline and 2-6 years after the A\(\beta\) assessment. Furthermore, we reported that worse TUG performance at baseline was associated with a greater risk of cognitive decline 2 years later, suggesting that FC performance may be linked to better cognitive outcomes over a 2-year period. However, it requires maintenance, as baseline impact wanes over 2 years; hence, those maintaining TUG showed the best outcomes. With an increasing emphasis on early diagnosis, to allow people with dementia and their families earlier access to cost-effective interventions to delay cognitive loss and improve quality of life, global policy has recommended that primary care play a most important role in pre-diagnosis evaluation [3]. For this reason, if a simple test, such as the TUG, which is easily applied in clinical consultations, helps to predict the possible cognitive deterioration an individual may experience two years in advance, it would be a great help. In addition, through the mediation models, we provide statistical evidence suggesting that greater TUG performance at baseline may be associated with reduced risk of cognitive impairment through lower brain A\(\beta\) deposition, maintaining this process for up to 2 years--a longitudinal association that has never been shown before in the existing literature (to the Authors' knowledge). Moreover, we also observed the direct effect of TUG at baseline on the risk of cognitive impairment at 2 years, such that better FC performance showed both direct and indirect associations with cognitive outcomes. These results are partially in line with previous studies, in which A\(\beta\) mediated the relationship between PA and cognitive impairment [28; 31]. By contrast, a recent study analyzing the effect of lifestyle on A\(\beta\) burden and cognition by sex observed that elevated A\(\beta\) burden tends to increase cognitive impairment, although PA only showed a significantly beneficial effect in men, not women [31]. Although these results are contrary to ours, it should be noted that the questionnaires and accelerometers provide the amount of PA the subjects engage in at a given moment or period, whereas functional capacity is objective data on a person's physical capacity. This fact may be one of the causes of the discrepancies in the said study. Considering the existing literature, findings regarding the relationship between PA and A\(\beta\) burden are mixed. It may be because most of the findings were obtained through cross-sectional or longitudinal studies, in which some of the measures of interest were assessed only at baseline (for example, PA). In the present study, almost 50% of the samples significantly decreased FC performance over time. However, longitudinal analysis revealed that significant cognitive decline was observed only in women with amyloidosis (A\(\beta\)+ = SUVR \(\geq\) 1.42) compared to those with low or intermediate A\(\beta\) burden. Maintaining or improving FC over time was associated with a reduced risk of cognitive impairment related to A\(\beta\) deposition in A\(\beta\)+ older women. This result agrees with the finding previously reported by [PERSON] et al.