The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

Early neuropathological changes characteristic of late-onset Alzheimer’s disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep–wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer’s disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep–wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler’s vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep–wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.

The natural history of preclinical late-onset Alzheimer´s disease (LOAD) remains obscure and has received less attention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With the purpose of detecting early structural and functional traits associated with the disorder, we sought to characterize cortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in persons at risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images for gray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detect fibrillar amyloid deposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed with LOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS). We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral metabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippocampal volume and hippocampal metabolism.Given the importance of age in this sample of individuals presumably developing early AD-related changes, we controlled results for age and observed that most differences in cortical thickness and metabolism became nonsignificant; however, greater deposition of β-amyloid was observed in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior and middle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, 4 and amyloid changes in cognitively normal persons with family history of LOAD may bear important implications for the definition of very early phenotypes of this disorder.

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Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer's disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer's disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms. Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases.Structural correlates of both cognitive dimensions were different in CS and O-LOAD, involving brain regions concerned with autonomic, motor, and motivational control in the former, and regions traditionally implicated in Alzheimer's disease in the latter. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD. The neuroimaging correlates of such cognitive measure in those with one parent with LOAD involve Alzheimer's-relevant brain regions even at a relatively young age.

Aging is associated with weakening of the circadian system. The circadian amplitude of most physiological variables is reduced, while the circadian phase becomes more labile and tends to occur earlier with advancing age. As the incidence of falls in older persons could follow circadian variations, a better understanding of conditions in which falls occur can lead to the implementation of countermeasures (such as adjusting the scheduling of hospital staff, or changing the timing of anti-hypertensive medication if falls are related to undesirable circadian patterns of blood pressure and/or heart rate). This includes knowing the times of the day, days of the week, and times of the year when falls are more likely to occur at home or in the hospital. Additionally, the links between aging processes and factors associated with an increased risk of developing autonomic dysfunction are well established. A strong association between heart rate variability indexes and aging has been shown. Circadian rhythms of autonomous nervous system activity may play important role for maintenance of orthostatic tolerance. Whether one is concerned with disease prediction and prevention or maintenance of healthy aging, the study of circadian rhythms and the broader time structure underlying physiopathology is helpful in terms of screening, early diagnosis and prognosis, as well as the timely institution of prophylactic and/or palliative/curative treatment. Timing the administration of such treatment as a function of circadian (and other) rhythms also could lead to reduction of falls in older persons. Finally, a prominent circadian rhythm characterizes melatonin, which peaks during the night. The circadian amplitude of melatonin decreases as a function of age, raising the questions whether such a decrease in the circadian amplitude of melatonin relates to a higher risk of falls and, if so, whether melatonin supplementation may be an effective countermeasure. This narrative review assesses the relationships between fall risk and the potential role circadian rhythms and melatonin play in mitigating this risk. We aim to provide healthcare workers adequate information about fall risk in older persons, including the potential role of the circadian rhythms and/or melatonin, as well as to lay foundations for future fall prevention interventional studies.

Working in extreme environments requires a wide range of cognitive, psychological and social competences. Antarctica represents one of the most challenging habitats to work in due to its aridity, extremely cold weather, and isolated conditions. This study aimed to assess mood variations and coping strategies, as well as their possible modulation by group dynamics in a crew at the Belgrano II Argentine Antarctic Station throughout 1 year of confinement. Thirteen members of the Argentine Army completed emotional, coping and social dynamics questionnaires bimonthly in March, May, July, September and November. Results showed a significant decline in social dynamics scales, evidenced by decreases in perceived peer and hierarchical support. Additionally, coping strategies displayed a drop in mature defence throughout the expedition. A positive correlation was found between social support and recovery from stress. Our results highlight the importance of interpersonal relationships in psychological adjustment to isolation and extreme environments.