# The Link Between Physical Function, \(\beta\)-Amyloid, and Cognitive Aging in Women
## 1 Introduction  
The life expectancy that developed countries have experienced in recent decades, together with medical advances, has led to an exponential increase in the number of people reaching an advanced age. For this reason, diseases that in the past were not present in many people have today become the leading causes of morbidity and mortality. Dementia is one of the costiliest long-term illnesses to society, with 85% of costs related to family or social care [1], and is associated with difficulties in performing daily activities and a reduced quality of life [2]. The latest reports establish that around 55 million people have dementia worldwide [3], with Alzheimer's disease (AD) being the most common form of dementia. Furthermore, it is worth mentioning that AD disproportionately affects women, both in prevalence and severity.  
Alzheimer's disease is a progressive, neurodegenerative disease that occurs when nerve cells in the brain die. The pathophysiological process of AD begins decades before clinical symptoms emerge and is characterized by early brain beta-amyloid (A\(\beta\)) deposition taking place in senile plaques and cerebrovascular deposits [4]. Evidence suggests that the accumulation of A\(\beta\) is one of the first biomarkers of AD and a hallmark of a downstreamchain of events, which eventually causes neurodegeneration, cognitive impairment, and finally, dementia [5]. Currently, there are no effective pharmacological treatments that can stop or significantly slow the disease. Thus, determining the modifiable factors that may delay and even prevent disease is clinically important.  
Physical activity (PA) is considered an essential modifiable factor related to cognitive function, being associated with a lower incidence of dementia, including AD [6]. A physically active lifestyle may prevent dementia through several pathways, such as improving cerebral vascularization, blood flow, and antioxidant and inflammatory processes in the brain, as well as decreasing A\(\beta\) production and increasing A\(\beta\) clearance [7; 8]. In the same way, PA has indirect pathways through improvements in mood, sleep, and other cardiovascular risk factors. However, there are limitations when assessing PA using both subjective and objective methods, as they often do not accurately reflect personal physical performance. For this reason, evaluating physical functional capacity (FC) has been identified as an objective measure, a reflection of individual physical fitness positively associated with many health indices and as an early predictor of brain deterioration [9; 10]. Nevertheless, the association between FC and AD biomarkers has not been consistently replicated, particularly regarding brain A\(\beta\) deposition. In a recent study published by our group [11], we reported that higher FC performance was associated with lower brain A\(\beta\) deposition. However, it is essential to note that much of the evidence to date comes from cross-sectional studies or short follow-ups likely to reverse causality [12].  
The primary goals of the current study are (a) to assess the association between baseline FC and brain A\(\beta\) burden with longitudinal cognitive performance in cognitively healthy older women, and (b) to examine the association between changes in FC performance over time and baseline brain A\(\beta\) burden with longitudinal cognitive decline.