Aim To parse out the impact of advanced ageing and disuse on skeletal muscle function, we utilized both in vivo and in vitro techniques to comprehensively assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25±6yrs) and 8 oldest-old mobile (OM; 87±5yrs) and 8 immobile (OI; 88±4yrs) women. Methods In vivo, maximal voluntary contraction (MVC), electrically evoked resting twitch force (RT), and physiological cross sectional area (PCSA) of the quadriceps and elbow flexors was assessed. Muscle biopsies of the vastus lateralis and biceps brachii facilitated the in vitro assessment of single fibre specific tension (Po). Results In vivo, compared to the young, both the OM and OI exhibited a more pronounced loss of MVC in the lower-limb (OM (−60%) and OI (−75%)) than the upper-limb (OM=−51%; OI=−47%). Taking into account the reduction in muscle PCSA (OM=−10%; OI=−18%), only evident in the lower-limb, by calculating voluntary muscle specific force, the lower-limb of the OI (−40%) was more compromised than the OM (−13%). However, in vivo, RT in both upper- and lower-limbs (~9.8 N·m·cm−2) and Po (~123 mN·mm−2), assessed in vitro, implies preserved intrinsic contractile function in all muscles of the oldest-old and were well correlated (r=0.81). Conclusion These findings suggest that in the oldest-old neither advanced ageing nor disuse, per se, impact intrinsic skeletal muscle function, as assessed in vitro. However, in vivo, muscle function is attenuated by age and exacerbated by disuse, implicating factors other than skeletal muscle, such as neuromuscular control, in this diminution of function.

Sundowning syndrome (SDS) in patients with Alzheimer's disease (AD) is characterized by the intensification of behavioral disorders at sunset. Despite SDS etiology being unclear, a strong relationship between high cortisol levels and SDS has been reported. Aerobic exercise (AE) and cognitive training (CT) can reduce cortisol levels. However, whether SDS would benefit from AE and CT is still unknown. Therefore, the aim of this study was to investigate whether AE and CT treatments are effective in reducing SDS via downregulation of cortisol levels. The possible additive effects of combined AE+CT were also assessed. Eighty AD patients were randomly assigned to AE (n = 20), CT (n = 20), AE+CT (n = 20), and standard therapy (no treatment, NT; n = 20). Treatments were administered for 3 months, 5 days/week, 1 hour before sunset. Before and after treatments, salivary cortisol levels were sampled at 7, 11, 15, at sunset, and 20 (time of day). Blind assessment of behavioral disorders (neuropsychiatric inventory, NPI) and agitation (agitated behavior scale, ABS) were also performed. After interventions, cortisol levels were reduced in AE and AE+CT by ∼26%. In the same groups, NPI and ABS decreased by ∼50%. By contrast, cortisol and behavioral disorders were similar to baseline in CT and NT. Changes in NPI and ABS were significantly correlated with the reduction in cortisol levels. AE or AE+CT effects on SDS and cortisol levels and the lack of effect of CT alone indicate the effectiveness of an exercise-based treatment on SDS, suggesting a possible hypothalamic-pituitary-adrenal axis dysregulation underpinning SDS.

Background: Behavioral and psychological symptoms of dementia (BPSD) affect 60-90% of patients with Alzheimer's disease (AD). Objective: To determine if environmental therapy is an effective strategy to reduce BPSD, we tested 163 patients with AD with Neuropsychiatric Inventory (NPI) before and after 6 months of an indoor therapeutic garden (TG) or standard environment. Methods: A single-blind randomized controlled trial on AD patients with BPSD. Participants were randomized to an indoor TG (N = 82), or standard environment (control, N = 81) for 6 months. Primary outcome: change in the NPI score from baseline (T0) to end of treatment (T1). Secondary outcomes: change in use of quetiapine, cognition, activities of daily living, salivary cortisol, blood pressure from T0 to T1. Results: NPI score significantly ameliorated (TG versus control: -31.8 points), quetiapine dosage (-150 mg), blood pressure (-2.6 mm Hg), and salivary cortisol (-6.4 to -2.1 Nmol/l) were significantly reduced, the Mini-Mental State Examination significantly improved (1.8 points) in the TG versus control arm at T1 (p < 0.001). No adverse events were reported. Conclusion:The indoor TG seems safe and may reduce BPSD, medication intake, and cortisol levels in AD.

Cognitive and physical activity treatments (CT and PT) are two non-pharmacological approaches frequently used in patients with Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). The aim of this study was to compare CT and PT in these diseases. Eighty-seven patients were randomly assigned to CT (n=30), PT (n=27) or control group (CTRL; n=30) for 6 months. The global cognitive function was measured by Mini Mental State Examination (MMSE). Specific neuropsychological tests explored attention, memory, executive functions, behavioral disorders. Cardiovascular risk factors (CVD) were collected. All measures were performed before (T0), after treatments (T1), and at three-months follow-up (T2). MMSE did not change from T0 to T1 and T2 in patients assigned to PT and CT, while CTRL patients showed a decline MCI: -11.8%, AD: -16.2%). Between group differences (MCI vs AD) were not found at T1 and T2. Significant worsening was found for CTRL in MCI (T0- T1: P =.039; T0-T2: P <.001) and AD (T0-T1: P <.001; T0-T2: P <.001), and amelioration was found for CT in AD (T0-T2: P <.001). Attention, executive functions and behavioral disorders were unaffected by either PT or CT. Memory was increased in patients with MCI assigned to PT (+6.9%) and CT (+8.5%).. CVD were ameliorated in the PT group. CTRL patients of both groups, revealed significant decline in all functions and no between groups differences were detected. PT appear to ameliorate CVD. Although between groups differences were not found, results suggest a major retention in MCI compared with AD, suggesting that the latter might benefit better of constant rather than periodic treatments. This study confirms the positive effects of CT and PT in mitigating the cognitive decline in MCI and AD patients, and it is the first to demonstrate their similar effectiveness on maintaining cognitive function.

No abstract