REM sleep is reduced in late middle-aged and older APOE4 allele carriers.

STUDY OBJECTIVES: Apolipoprotein E ɛ4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD). In addition, APOE4 carriers may exhibit sleep disturbances, but conflicting results have been reported, such that there is no clear consensus regarding which aspects of sleep are impacted. Our objective was to compare objective sleep architecture between APOE4 carriers and non-carriers, and to investigate the modulating impact of age, sex, cognitive status and obstructive sleep apnea. METHODS: 198 dementia-free participants aged >55 years old (mean age: 68.7 ± 8.08 years old, 40.91% women, 41 APOE4 carriers) were recruited in this cross-sectional study. They underwent polysomnography, APOE4 genotyping and a neuropsychological evaluation. ANCOVAs assessed the effect of APOE4 status on sleep architecture, controlling for age, sex, cognitive status and the apnea-hypopnea index. Interaction terms were added between APOE4 status and covariates. RESULTS: REM sleep percentage (F=9.95, p=0.002, ηp2=0.049) and duration (F=9.23, p=0.003, ηp2=0.047) were lower in APOE4 carriers. The results were replicated in a subsample of 112 participants without moderate-to-severe obstructive sleep apnea. There were no significant interactions between APOE4 status and age, sex, cognitive status and obstructive sleep apnea in the whole sample. CONCLUSIONS: Our results show that APOE4 carriers exhibit lower REM sleep duration, including in cognitively unimpaired individuals, possibly resulting from early neurodegenerative processes in regions involved in REM sleep generation and maintenance.

REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals.

BACKGROUND: Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer's disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants. METHODS: Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status. RESULTS: In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (ß = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (ß = 0.48, p = 0.012) and total BF volumes (ß = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables. DISCUSSION: These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits.

Medial temporal lobe and obstructive sleep apnea: Effect of sex, age, cognitive status and free-water.

Medial temporal structures, namely the hippocampus, the entorhinal cortex and the parahippocampal gyrus, are particularly vulnerable to Alzheimer's disease and hypoxemia. Here, we tested the associations between obstructive sleep apnea (OSA) severity and medial temporal lobe volumes in 114 participants aged 55-86 years (35 % women). We also investigated the impact of sex, age, cognitive status, and free-water fraction correction on these associations. Increased OSA severity was associated with larger hippocampal and entorhinal cortex volumes in women, but not in men. Greater OSA severity also correlated with increased hippocampal volumes in participants with amnestic mild cognitive impairment, but not in cognitively unimpaired participants, regardless of sex. Using free-water corrected volumes eliminated all significant associations with OSA severity. Therefore, the increase in medial temporal subregion volumes may possibly be due to edema. Whether these structural manifestations further progress to neuronal death in non-treated OSA patients should be investigated.

Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial.

OBJECTIVE: To investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation improve cognitive performance and if apolipoprotein E (APOE) genotype or age were effect modifiers. METHODS: Healthy adults of 20 to 80 years old (n = 193) were completed a 6-month double-blind randomized controlled trial with two groups: 2.5 g/day of n-3 PUFA or a placebo. Primary outcomes were visuospatial ability and working memory and secondary outcomes were episodic memory and executive function, measured at baseline and 6 months. RESULTS: Cognitive performances did not significantly differ between groups on primary or secondary outcomes after 6 months of treatment. APOE carriers and age were not effect modifiers for any outcomes. Those with low episodic memory scores and taking the n-3 PUFA supplement, significantly improved their scores (p = 0.043). CONCLUSIONS: A 6-month n-3 PUFA supplementation did not improve cognitive performance in cognitively healthy adults and APOE status or age were not effect modifiers.

A portrait of obstructive sleep apnea risk factors in 27,210 middle-aged and older adults in the Canadian Longitudinal Study on Aging.

Determining the prevalence and characteristics of individuals susceptible to present with obstructive sleep apnea (OSA) is essential for developing targeted and efficient prevention and screening strategies. We included 27,210 participants aged ≥45 years old (50.3% women) from the Canadian Longitudinal Study on Aging. Using the STOP questionnaire combined to the percentage of body fat (%BF), we estimated the prevalence of individuals at high-risk for OSA in a sex and age-specific manner, and tested the relation with comorbidities, menopause and systemic inflammation. The prevalence was 17.5%, and was lower in women (13.1%) than in men (21.9%). A high level of high-sensitivity C-reactive protein was the strongest factor associated with OSA risk and this association was 1.3-2.3 times higher in women than in men. OSA risk increased with age, cardiovascular diseases, diabetes mellitus, anxio-depressive symptoms, asthma and arthritis. In women, post-menopausal status was associated with a high OSA risk. Nearly 1 adult out of 5 older than 45 is at risk for OSA in Canada. Comorbidities, menopause and systemic inflammation, more than age, explain increased OSA prevalence. Considering this high prevalence and associations with medical and mental comorbidities, health care practitioners should incorporate systematic OSA screening in their clinical procedures.

Association between risk of obstructive sleep apnea, inflammation and cognition after 45 years old in the Canadian Longitudinal Study on Aging.

BACKGROUND: The association between obstructive sleep apnea and cognitive functioning is not yet fully understood and could be influenced by factors such as sex, age and systemic inflammation. We determined the sex- and age-specific association between obstructive sleep apnea risk and cognitive performance, and the influence of systemic inflammation on this association. METHODS: We included 25,899 participants from the Canadian Longitudinal Study of Aging comprehensive cohort, aged 45-85 years (51% women). We conducted sex- and age-specific (45-59; 60-69; ≥70) general linear models between obstructive sleep apnea risk and cognitive scores, and tested the moderating and mediating effects of high-sensitivity C-reactive protein levels. Obstructive sleep apnea risk was estimated by combining the STOP and whole-body fat percentage. Cognitive tests assessed episodic verbal memory, executive functions and psychomotor speed. Levels of high-sensitivity C-reactive protein were obtained through blood samples. RESULTS: Higher obstructive sleep apnea risk was associated with poorer episodic memory in women aged 45-59 years, and poorer executive function (p < 0.05 on multiple tests) in women aged 45-59 and 60-69 years. No such association was found in men. High-sensitivity C-reactive protein levels mediated some associations between obstructive sleep apnea risk and executive function in women and men aged <70 years. CONCLUSIONS: Being at high-risk for obstructive sleep apnea is associated with poorer cognition in women aged <70 years. These associations were partly mediated by systemic inflammation. These results underscore the importance of obstructive sleep apnea diagnosis, treatment and appropriate follow-up, particularly in middle-aged women who might already show signs of early cognitive impairments.

Context awareness architecture for ambient-assisted living applications: Case study of nighttime wandering.

OBJECTIVES: This work presents an ambient-assisted living application that encourages seniors during nocturnal wandering episodes to return to bed in calm and comfort reassurance. METHODS: Structuring knowledge by designing a software architecture capable of delivering high-level analysis and processing. A senior's home has been upgraded into a smart home enabling the gathering of habits for two weeks and set up for personalized assistance over four weeks. Home automation devices associated with Actigraph monitors and self-reported sleep were used for more accuracy. RESULTS: The architectural model can be used in ambient-assisted living applications for which data collection is permanent and continuous. Its layered organization facilitates the management of specific and general activities of daily life. The results of the home experience show that the system gave a notification whenever the need arose. On the other hand, it allowed the caregiver to get more information about the lifestyle of the senior. CONCLUSIONS: Future work should focus on providing more services to contextualize assistance. Ontology is used to structure all the ambient knowledge of the smart home. We also plan to do more home experiments.

Tractography of the external capsule and cognition: A diffusion MRI study of cholinergic fibers.

INTRODUCTION: White matter changes (WMC) in the cholinergic tracts contribute to executive dysfunction in the context of cognitive aging. WMC in the external capsule have been associated with executive dysfunction. The objectives of this study were to: 1) Characterize the lateral cholinergic tracts (LCT) and the superior longitudinal fasciculus (SLF). 2) Evaluate the association between diffusion measures within those tracts and cognitive performance. METHODS: Neuropsychological testing and high angular resolution diffusion imaging (HARDI) of 34 healthy elderly participants was done, followed by anatomically constrained probabilistic tractography reconstruction robust to crossing fibers. The external capsule was manually segmented on a mean T1 image then merged with an atlas, allowing extraction of the LCT. Diffusion tensor imaging (DTI) and HARDI-based measures were obtained. RESULTS: Correlations between diffusion measures in the LCT and the time of completion of Stroop (left LCT radial and medial diffusivity), the Symbol Search score (right LCT apparent fiber density) and the motor part of Trail-B (left LCT axial and radial diffusivity) were observed. Correlations were also found with diffusion measures in the SLF. WMC burden was low, and no correlation was found with diffusion measures or cognitive performance. DISCUSSION: DTI and HARDI, with isolation of strategic white matter tracts for cognitive functions, represent complimentary tools to better understand the complex process of brain aging.

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

OBJECTIVE: The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. METHOD: We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). RESULTS: Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. DISCUSSION: As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD's hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

Early Detection of Mild Cognitive Impairment With In-Home Monitoring Sensor Technologies Using Functional Measures: A Systematic Review.

The aging of the world population is accompanied by a substantial increase in neurodegenerative disorders, such as dementia. Early detection of mild cognitive impairment (MCI), a clinical diagnostic that comes with an increased chance to develop dementias, could be an essential condition for promoting quality of life and independent living, as it would provide a critical window for the implementation of early pharmacological and nonpharmacological interventions. This systematic review aims to investigate the current state of knowledge on the effectiveness of smart home sensors technologies for the early detection of MCI through the monitoring of everyday life activities. This approach offers many advantages, including the continuous measurement of functional abilities in ecological environments. A systematic search of publications in MEDLINE, EMBASE, and CINAHL, before November 2017, was conducted. Seventeen studies were included in this review. Thirteen studies were based on real-life monitoring, with several sensors installed in participants' actual homes, and four studies included scenario-based assessments, in which participants had to complete various tasks in a research lab apartment. In real-life monitoring, the most used indicators of MCI were walking speed and activity/motion in the house. In scenario-based assessment, time of completion, quality of activity completion, number of errors, amount of assistance needed, and task-irrelevant behaviors during the performance of everyday activities predicted MCI in participants. Despite technological limitations and the novelty of the field, smart home technologies represent a promising potential for the early screening of MCI and could support clinicians in geriatric care.

Can we improve pain and sleep in elderly individuals with transcranial direct current stimulation? - Results from a randomized controlled pilot study.

BACKGROUND: The prevalence of chronic pain and sleep disturbances substantially increases with age. Pharmacotherapy remains the primary treatment option for these health issues. However, side effects and drug interactions are difficult to control in elderly individuals. AIMS: The objective of this study was to assess the feasibility of conducting a randomized sham-controlled trial and to collect preliminary data on the efficacy of transcranial direct current stimulation (tDCS) to reduce pain and improve sleep in older adults suffering from chronic pain. METHODS: Fourteen elderly individuals (mean age 71±7 years) suffering from chronic pain and sleep complaints were randomized to receive either anodal tDCS, applied over the primary motor cortex (2 mA, 20 minutes), or sham tDCS, for 5 consecutive days. Pain was measured with visual analog scales, pain logbooks and questionnaires, while sleep was assessed with actigraphy, sleep diaries and questionnaires. RESULTS: There were no missing data for pain and sleep measures, except for actigraphy, that generated several missing data. Blinding was maintained throughout the study, for both the evaluator and participants. Active but not sham tDCS significantly reduced pain (P<0.05). No change was observed in sleep parameters, in both the active and sham tDCS groups (all P≥0.18). CONCLUSION: The present study provides guidelines for the implementation of future tDCS studies in larger populations of elderly individuals. M1 anodal tDCS in this population appears to be effective to reduce pain, but not to improve sleep.

Normative Data for the Montreal Cognitive Assessment in Middle-Aged and Elderly Quebec-French People.

OBJECTIVE: Given that aging is associated with higher risk of cognitive decline and dementia, improving early detection of cognitive impairment has become a research and clinical priority. The Montreal Cognitive Assessment (MoCA) is a screening instrument used to assess different aspects of cognition. Despite its widespread use, norms adjusted to the sociodemographics of Quebec-French people are not yet available. Such norms are however important because performance on neuropsychological tests varies according to sociodemographic variables including age, sex, and education. As such, the present study aimed to establish normative data for the MoCA in middle-aged and elderly Quebec-French population. METHOD: For that purpose, 1,019 community-dwelling older adults aged between 41 and 98 were recruited. Participants from 12 recruiting sites completed the MoCA. Regression-based normative data were produced and cross-validated with a validation sample (n = 200). RESULTS: Regression analyses indicated that older age, lower education level, and male sex were associated with poorer MoCA scores. The best predictive model included age (p < .001), education (p < .001), sex (p < .001), and a quadratic term for education (education X education; p < .001). This model explained a significant amount of variance of the MoCA score (p < .001, R2 = 0.26). A regression equation to calculate Z scores is presented. CONCLUSIONS: This study provides normative data for the MoCA test in the middle-aged and elderly French-Quebec people. These data will facilitate more accurate detection and follow-up of the risk of cognitive impairment in this population, taking into account culture, age, education, and sex.

Alterations in Monocyte Phenotypes and Functions after a Hip Fracture in Elderly Individuals: A 6-Month Longitudinal Study.

BACKGROUND: Healthy elderly individuals are particularly prone to catastrophic events at any moment of their lives. One stressful event for individuals aged 65 and older is a fall that results in a fracture of the hip (HF). HF causes a state of inflammation that may affect immune responses. In this connection, we have reported that HF induced alterations in neutrophil functions. OBJECTIVE: To assess the impact of HF on classical (cM), intermediate (iM) and non-classical (ncM) monocyte subsets. METHODS: Distribution, functions (chemotaxis, phagocytosis, superoxide production and cytokine production), phenotype and activation (NF-x03BA;B and PI3K) were evaluated in monocyte subsets before surgery and 6 weeks and 6 months after the event. RESULTS: The distribution of cM and ncM was unchanged, but iM transiently increased before surgery. Sustained increases (iM response to CCL2 and CX3CL1) and decreases (cM and ncM response to CCL2) in chemotaxis were observed. Phagocytosis and superoxide production were impaired in cM but not in iM or ncM. Sustained expression of HLA-DR occurred in cM but not in iM and ncM. Sustained decreased expression of CD11b occurred only in ncM. Sustained decreases (cM and ncM) and increases (iM) in CCR2 expression were observed. An elevated expression of CX3CR1 was found only in iM. cM produced elevated quantities of TNFα. There was a transient oxidative burst of production before surgery in iM and a sustained decrease in ncM. IL-10 production was severely impaired in cM and decreased in iM prior to surgery. Sustained activation (cM), inhibition (ncM) and transient activation (iM) of NF-x03BA;B were observed. Activation of PI3K was severely impaired in cM and ncM but was sustained in iM. CONCLUSION: HF had more impact on cM and ncM functions than on iM. HF triggered a switch in cM functions from phagocytic to inflammatory elevated TNFα-producing cells. These changes may impact clinical outcomes of HF with respect to inflammation, opportunistic infections and physical recovery.

Guided self-help for generalized anxiety disorder in older adults.

OBJECTIVE: The main objective of this study was to examine the efficacy of a guided self-help treatment based on cognitive behavioral principles (CBT-GSH) for generalized anxiety disorder (GAD) in older adults. METHODS: Three older adults aged from 66 to 70 and diagnosed with GAD were included in a single-case experimental multiple-baseline protocol. Data were collected using daily self-monitoring, standardized clinician ratings, and self-report questionnaires at pretest, posttest, and 6-month and 12-month follow-ups. Treatment consisted of awareness training, worry interventions, relaxation training, pleasant activities scheduling, and relapse prevention. Participants used a manual presenting weekly readings and at-home practice exercises. They also received weekly supportive phone calls from a therapist. RESULTS: At posttest, participants showed improvement on worries and GAD severity, on psychological process variables targeted by treatment (intolerance of uncertainty, negative problem orientation, cognitive avoidance, and perceived usefulness of worry), and on secondary variables associated with GAD (anxiety, depression, sleep difficulties, cognitive functioning, and disability). These results were generally maintained at 12 months after the end of treatment. Participants had favorable opinions toward the treatment. CONCLUSION: The results of this study suggest that CBT-GSH is both feasible and effective for the treatment of GAD in older adults.

Significance of Non-phase Locked Oscillatory Brain Activity in Response to Noxious Stimuli.

BACKGROUND: Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. METHODS: In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. RESULTS: Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. CONCLUSION: This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. PERSPECTIVE: This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

Altered neutrophil functions in elderly patients during a 6-month follow-up period after a hip fracture.

BACKGROUND: Fracture of the hip (HF) is a significant cause of morbidity and mortality in elderly individuals. HF is an acute stress that triggers a state of inflammation which may affect immune responses and physical recovery. METHODS: Longitudinal study of the impact of HF on the functions of polymorphonuclear neutrophils (PMNs) in elderly subjects. Data were recorded prior to surgery, 6weeks and 6months later. RESULTS: PMN functions were severely impaired shortly after HF (chemotaxis, phagocytosis, superoxide production) but there was a time-related recovery of some PMN functions (chemotaxis, phagocytosis) over time, except in the case of superoxide production. Whereas FcγRII (CD32) expression remained unchanged, FcγRIII (CD16) increased from low values before surgery to levels of controls 6months post-surgery. This was also the case for the C5a complement receptor and CD11b. TLR2 and TLR4 expressions were unchanged. Cytokine and chemokine secretions by stimulated PMN were altered. TNFα and IL-10 secretions were increased following HF but IL-8 secretion was decreased. Impaired PMN functions prior to surgery were related to alterations in PI3K and NF-κB signaling pathways. Recovery of these functions paralleled increased PI3K activity, although superoxide production remained low. Sustained activation of the NF-κB pathway by TNFα has been reported to involve upregulation of IKKß kinase activity. Activated IKKß kinase inhibits ERK1/2 and results in concomitant downstream inhibition of NADPH oxidase complex which can account for sustained impaired production of ROS in HF patients. CONCLUSION: Our data showed that the stress caused by HF negatively affects initial PMN responses shortly after the event and that may negatively influence clinical outcomes such as resolving long-term inflammation and recovery, as well as explaining susceptibility to opportunistic infections.

Sleep depth and continuity before and after chronic exercise in older men: electrophysiological evidence.

During later life sleep depth (slow-wave sleep, SWS) and maintenance exhibit deleterious changes, with possible negative effects on daytime function. This study assessed the effect of chronic, supervised exercise on sleep using laboratory-based polysomnography (PSG) and repeated measures in older adults. Thirteen men aged 64±3served as their own controls and had their sleep measured for a total of 6 nights: 3 before and 3 after the 16-week training intervention. Each sequence involved 1 familiarization trial followed by 2 experimental nights (exercise night; nonexercise night) measured using 13-channel PSG (combined electroencephalography, electromyography, and electro-oculography). The exercise challenges consisted of inclined treadmill brisk walking (60min, 68-69% V˙O2peak). The intervention successfully improved some parameters of aerobic fitness, i.e. ventilatory thresholds 1 and 2 (P<0.05). Acute exercise triggered increases in circulating free fatty acids and lactate levels both at baseline and after the intervention (P<0.05). Noteworthy, acute exercise following training resulted in a 71% increase in SWS during subsequent sleep in comparison with the nonexercise condition before training, respectively 2.4% and 1.4% (P<0.05). Following training, acute exercise reduced total wake time by 30% and REM onset latency by 14% (P<0.05). Acute exercise improved sleep continuity by decreasing total wake time. These results show that aerobic training could increase sleep depth and continuity, during active days, in elderly men. In habitual exercisers, these effects of aerobic exercise on sleep, although modest, might counteract those resulting from aging.

Changes in markers of brain serotonin activity in response to chronic exercise in senior men.

Aging is associated with noticeable impairments in brain serotonin transmission, which might contribute to increased vulnerability to developing depression in later life. Animal and human studies have shown that aerobic exercise can stimulate brain serotonin activity and trigger parallel elevations in tryptophan (TRP, the serotonin precursor) availability in blood plasma. However, the influence of chronic exercise on serotonergic activity in older adults is not yet known. Sixteen men aged 64 ± 3 years exercised for 1 h (67%-70% peak oxygen consumption) at baseline and following 16 weeks of aerobic training. The main outcome measures were cardiorespiratory fitness, body composition, branched-chain amino acids (BCAA), TRP, prolactin, lactate, and free fatty acids (FFA). Changes in plasma free-TRP/BCAA and prolactin served as surrogates for TRP availability and serotonin activity, respectively. Chronic exercise decreased body mass (P < 0.05) whilst it increased ventilatory threshold 2 (P < 0.01). Although training did not affect plasma TRP availability to the brain at rest, both pre- and post-training exercise challenges markedly increased TRP availability (P < 0.001). The free-TRP/BCAA values reached a ceiling during exercise that was lower following training (P < 0.05), whereas similar patterns were found for prolactin, lactate, and FFA. These data show that aerobic exercise elicits consistent transient elevations in plasma TRP availability to the brain in older men; the elevations were independent from physical training, although less pronounced following training. The data support the contention that repeated elevations in brain serotonin activity might be involved in the antidepressant effect of exercise training in older adults.

Kinetics of 13C-DHA before and during fish-oil supplementation in healthy older individuals.

BACKGROUND: Docosahexaenoic acid (DHA) kinetics appear to change with intake, which is an effect that we studied in an older population by using uniformly carbon-13-labeled DHA ((13)C-DHA). OBJECTIVE: We evaluated the influence of a fish-oil supplement over 5 mo on the kinetics of (13)C-DHA in older persons. DESIGN: Thirty-four healthy, cognitively normal participants (12 men, 22 women) aged between 52 and 90 y were recruited. Two identical kinetic studies were performed, each with the use of a single oral dose of 40 mg (13)C-DHA. The first kinetic study was performed before participants started taking a 5-mo supplementation that provided 1.4 g DHA/d plus 1.8 g eicosapentaenoic acid (EPA)/d (baseline); the second study was performed during the final month of supplementation (supplement). In both kinetic studies, blood and breath samples were collected ≤8 h and weekly over 4 wk to analyze (13)C enrichment. RESULTS: The time × supplement interaction for (13)C-DHA in the plasma was not significant, but there were separate time and supplement effects (P < 0.0001). The area under the curve for plasma (13)C-DHA was 60% lower while subjects were taking the supplement than at baseline (P < 0.0001). The uniformly carbon-13-labeled EPA concentration was 2.6 times as high 1 d posttracer while patients were taking the supplement as it was at baseline. The mean (±SEM) plasma (13)C-DHA half-life was 4.5 ± 0.4 d at baseline compared with 3.0 ± 0.2 d while taking the supplement (P < 0.0001). Compared with baseline, the mean whole-body half-life was 61% lower while subjects were taking the supplement. The loss of (13)C-DHA through ß-oxidation to carbon dioxide labeled with carbon-13 increased from 0.085% of dose/h at baseline to 0.208% of dose/h while subjects were taking the supplement. CONCLUSIONS: In older persons, a supplement of 3.2 g EPA + DHA/d increased ß-oxidation of (13)C-DHA and shortened the plasma (13)C-DHA half-life. Therefore, when circulating concentrations of EPA and DHA are increased, more DHA is available for ß-oxidation. This trial was registered at clinicaltrials.gov as NCT01577004.

Subjective sleep characteristics associated with anxiety and depression in older adults: a population-based study.

OBJECTIVE: Sleep complaints are often associated with anxiety and depression, but the specific complaints related to each syndrome are poorly characterized, especially in older adults. The objective was to identify subjective sleep characteristics specific to anxiety and depression in this population. METHODS: A random sample of 2393 individuals aged 65 years or older was used. Anxiety and depression were categorized using DSM-V criteria for phobias, panic disorder, generalized anxiety disorder, unspecified anxiety disorder, major depressive episode, and depressive episode with insufficient symptoms. Subjective sleep characteristics were measured using the Pittsburgh Sleep Quality Index. Logistic regression models predicting anxiety or depression were used to determine the independent sleep characteristics associated with each syndrome adjusting for age, sex, education level, cognitive functioning, anxiolytic/sedative/hypnotic use, antidepressants use, subjective health, chronic diseases, cardiovascular conditions, and anxiety or depression (as appropriate). RESULTS: Nearly all Pittsburgh Sleep Quality Index subscales were significantly associated with anxiety, but these subscales shared variance and only sleep duration in hours, sleep disturbance score, and daytime functioning score were independently related to anxiety. Within these significant subscales, the main specific sleep complaints associated with anxiety were daytime sleepiness and sleep disturbances related to coughing/snoring, feeling cold, and bad dreams. The use of sleeping medication was the only specific sleep characteristic associated with depression. CONCLUSIONS: These results suggest that in older adults, symptoms of short sleep duration, daytime sleepiness and sleep disturbances are independently related to anxiety while the use of sleep medication is independently associated to depression.