On the other hand it is important to note

On the other hand, it is important to note that FR is different from the regulation of daily/circadian rhythms [44]. Based on models of physical systems [45], [46], it has been hypothesized that fractal physiological fluctuations reflect a network of elaborate regulatory processes interacting across multiple system components over a range of temporal and spatial scales [1]. Our animal study showed that the suprachiasmatic nucleus itself cannot generate fractal patterns [47], supporting the network 2188 synthesis of FR. Moreover, we found in this study that fractal activity regulation predicts AD and MCI, independent of the two accepted circadian/sleep measures (i.e., sleep fragmentation and daily activity stability). Therefore, future studies are required to determine the neural circuitry for FR and the neuroanatomical/neuropathological changes underlying the altered FR observed in those individuals at risk for AD. Despite the lack of fully mechanistic understanding of FR, a few recent studies have explored possible interventions that can improve or maintain FR. For instance, an animal study showed that maintaining a high physical activity level can help counteract the adverse effect of aging on FR [48]. In older adults in the middle-to-late stages of dementia, increased daily light exposure may diminish or even abolish the aging-induced degradation of FR [11]. Whether improving FR symptomatically using exercise and/or light interventions can help prevent or delay the onset of cognitive impairment merits further investigations. Population aging is widespread across the world. How to monitor health status of the elderly reliably and cost efficiently is a contemporary challenge. Related to AD, one of the important tasks is to identify individuals at a higher risk for AD at an earlier stage when interventions may be more effective [49], [50], [51], [52]. The rapid advances in the technology of wearable devices for assessment of daily activities provide new opportunities to address the challenge. In recent years, actigraphy has become frequently used to examine physical activity in clinical and research studies because the unobtrusive monitoring requires less cooperation from participants, allowing their usual daily behaviors [21], [22], [53]. In this study, we further demonstrated the value of an actigraphic measure based on nonlinear dynamic theory—FR—for predicting MCI and AD risk. Though our findings strongly suggest the potential value of FR in AD research, a number of questions are yet to be answered. First, most of the participants in the present study were older than 65 years and primarily non-Latino whites. Can FR at young ages (<65 years) predict cognitive decline and incident AD dementia and MCI? Is the predictability of FR different in different racial and ethnic minorities? In addition, FR in motor activity can be temporarily affected by transient disruptions of sleep-wake cycles and circadian control (e.g., night shifts) [43]. How should actigraphic data be collected to avoid such transient, “masking” effect on FR? Besides, 9-hour continuous activity data are technically adequate to estimate FR at <1.5 hours [10], [13], [14]. Indeed, for healthy young subjects, we showed that the fractal activity measure at <90 min was stable from day to day [14]. However, whether cortisol is stable in older subjects, especially those with dementia/AD, is not clear. Moreover, we only considered AD dementia. How specifically can FR alterations reflect AD neuropathology? How is FR affected by other types of neurodegenerative diseases such as Lewy bodies, Parkinson's disease, vascular dementia, and frontotemporal dementia that all can lead to dementia? Follow-up studies are necessary to provide answers to these questions before the application of FR measures to diagnosis of preclinical AD.
Introdução A doença de Alzheimer é a forma mais comum de demência da atualidade, estima‐se que atinja 26,6 milhões de pessoas em todo o mundo, cerca de 5% da população com mais de 65 anos. A descoberta de uma possível deterioração cognitiva como resultado de um evento anestésico/cirúrgico conduziu à investigação desse fenômeno, motivada também pela maior preocupação e procura de informação por parte dos doentes e das suas famílias.