Gait impairments in Alzheimer’s disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual’s biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health Functioning (ICF) to classify and describe the functioning and disability on gait and exploratory activity in the 3xTg-AD animal model. We developed a behavioral observation method that allows us to differentiate qualitative parameters of psychomotor performance in animals’ gait, similar to the behavioral patterns observed in humans. The functional psychomotor evaluation allows measuring various dimensions of gait and exploratory activity at different stages of disease progression in dichotomy with aging. We included male 3xTg-AD mice and their non-transgenic counterpart (NTg) of 6, 12, and 16 months of age (n = 45). Here, we present the preliminary results. The 3xTg-AD mice show more significant functional impairment in gait and exploratory activity quantitative variables. The presence of movement limitations and muscle weakness mark the functional decline related to the disease severity stages that intensify with increasing age. Motor performance in 3xTg-AD is accompanied by a series of bizarre behaviors that interfere with the trajectory, which allows us to infer poor neurological control. Additionally, signs of physical frailty accompany the functional deterioration of these animals. The use of the ICF as a conceptual framework allows the functional status to be described, facilitating its interpretation and application in the rehabilitation of people with AD.

One year after the start of the COVID-19 pandemic, its secondary impacts can be globally observed. Some of them result from physical distancing and severe social contact restrictions by policies still imposed to stop the fast spread of new variants of this infectious disease. People with Alzheimer's disease (AD) and other dementias can also be significantly affected by the reduction of their activity programs, the loss of partners, and social isolation. Searching for the closest translational scenario, the increased mortality rates in male 3xTg-AD mice modeling advanced stages of the disease can provide a scenario of “naturalistic isolation.” Our most recent work has shown its impact worsening AD-cognitive and emotional profiles, AD-brain asymmetry, and eliciting hyperactivity and bizarre behaviors. Here, we further investigated the psychomotor function through six different psychomotor analysis in a set of 13-month-old 3xTg-AD mice and their non-transgenic counterparts with normal aging. The subgroup of male 3xTg-AD mice that lost their partners lived alone for the last 2–3 months after 10 months of social life. AD's functional limitations were shown as increased physical frailty phenotype, poor or deficient psychomotor performance, including bizarre behavior, in variables involving information processing and decision-making (exploratory activity and spontaneous gait), that worsened with isolation. Paradoxical muscular strength and better motor performance (endurance and learning) was shown in variables related to physical work and found enhanced by isolation, in agreement with the hyperactivity and the appearance of bizarre behaviors previously reported. Despite the isolation, a delayed appearance of motor deficits related to physical resistance and tolerance to exercise was found in the 3xTg-AD mice, probably because of the interplay of hyperactivity and mortality/survivor bias. The translation of these results to the clinical setting offers a guide to generate flexible and personalized rehabilitation strategies adaptable to the restrictions of the COVID-19 pandemic.

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