Mental Fatigability Research Articles

Relationship Between Personality Measures and Perceived Mental Fatigability.

Examine the association between personality measures and perceived mental fatigability. We performed a cross-sectional analysis in N=1670 men, age 84.3±4.1 years. Multivariable linear regression models were used to examine the covariate adjusted association between personality measures (conscientiousness, optimism, goal reengagement, and goal disengagement) and perceived mental fatigability (measured with the validated 10-item Pittsburgh Fatigability Scale, PFS). One standard deviation lower conscientiousness (β=-0.91, p<.0001) and optimism (β=-0.63, p<.0001), and higher goal reengagement (β=0.51, p=.01) scores were independently associated with higher PFS Mental scores adjusted for age, cognitive function, self-reported health status, depressive symptoms, sleep disturbance, physical activity, and goal disengagement. Lower conscientiousness, optimism, and higher goal reengagement were linked with more severe perceived mental fatigability in older men. Personality traits may potentially contribute to early risk assessment for fatigability in later life. Future work should be longitudinal in nature and include personality assessments to confirm the temporality of the relationships observed.

Life-space Mobility in Older Men: The Role of Perceived Physical and Mental Fatigability.

Physical performance and fatigue can limit mobility within the larger environment (life-space mobility). It is unknown whether perceived fatigability, self-reported fatigue anchored to activity intensity and duration, is independently associated with life-space. We assessed this cross-sectionally in Visit 4 (2014-2016) of the Osteoporotic Fractures in Men Study (MrOS; N = 1 672, Age: Mean = 84.2 ± 4.0 years). The Pittsburgh Fatigability Scale (PFS, range: 0-50; higher = greater fatigability) measured physical (Mean = 16.1 ± 9.4) and mental fatigability (Mean = 7.5 ± 7.9). Life Space Assessment scores incorporated level, frequency, and assistance used for life-space mobility (range: 0-120, higher = greater life-space mobility; life-space constriction: inability to leave neighborhood without assistance). Separate multiple linear and logistic regressions for physical and mental fatigability were sequentially adjusted for demographic, health/lifestyle, and performance measures. The mean life-space mobility score was 84.6 ± 21.8, and 18% (n = 296) of men had life-space constriction. Higher physical and mental fatigability were both associated with lower life-space mobility in models adjusted for health and lifestyle factors (Physical PFS: B = -2.37, 95% confidence interval [CI]: [-3.39, -1.35]; Mental PFS: B = -1.79, 95% CI: [-2.73, -0.84]). Men with higher fatigability also had increased risk of life-space constriction (Physical PFS: OR = 1.59, 95% CI: [1.32, 1.92]; Mental PFS: OR = 1.25, 95% CI: [1.08, 1.46]). Associations were larger in magnitude for physical versus mental fatigability. Adjusting for physical performance measures more strongly attenuated associations for physical compared to mental fatigability. Fatigability is linked with real-world mobility in older men, independent of their physical health. This association may be driven by separate physical and cognitive mechanisms worth examining further in longitudinal studies.

Different properties of the hemodynamic response and its relation to trait mental fatigue and proactive cognitive control

IntroductionThe Dual Mechanism of Control theory proposes that we use our cognitive control in a proactive and reactive mode. The proactive mode is used to optimize performance in more challenging tasks and is thought to be a more demanding activity. Trait mental fatigue is the overall disposition of mental fatigability and sensation of mental weariness and exhaustion. In the present study, we investigated the association between trait mental fatigue, proactive control, and different properties of the hemodynamic response in the frontal and parietal cortex of healthy adults. Method30 healthy adults answered the Mental Fatigue Scale (MFS), performed the AX-Continuous Performance Task (AX-CPT), a test of proactive cognitive control which generates the proactive behavioral index (PBI), and underwent functional near-infrared spectroscopy (fNIRS) to measure functional activity in the frontal and parietal cortex while being tested on the AX-CPT. ResultThere was a Spearman's correlation ρ = −0.462 between MFS and the PBI, indicating an association between trait mental fatigue and a tendency to rely on reactive cognitive control. The exploratory analysis indicated that higher trait mental fatigue was associated with higher oxygenated hemoglobin concentrations (oxy-Hb) and total hemoglobin (tot-Hb) from the initial dip to up to the peak during reactive situations. This was observed bilaterally in the medial posterior partial (MPPC) cortex and the right lateral palatal cortex (LPC) for oxy-Hb. In contrast, for tot-Hb, this pattern was also observed in the left dorsolateral prefrontal cortex (DLPFC) and right anterior DLPFC, bilateral MPPC, right lateral PPC, and right parietal cortex. Individuals with a more reactive response type showed during proactive situations a higher concentration of oxy-Hb and tot-Hb in the right MPPC and the right LPPC for oxy-Hb for the latter part of the hemodynamic response. Discussion/conclusionHigher trait mental fatigue is associated with a tendency to favor reactive over proactive cognitive control in healthy adults. fNIRS imaging detected the involvement of several brain regions in trait mental fatigue. However, further research is needed to determine whether the hemodynamic response function could be linked to suboptimal neurovascular coupling.

Comparison of fatigue and fatigability correlates in Korean breast cancer survivors and differences in associations with anxiety, depression, sleep disturbance, and endocrine symptoms: a randomized controlled trial

BackgroundFatigue is one of the most common and burdensome symptoms experienced by cancer patients. In interventions intended to reduce fatigue in such patients, fatigability, or perception of fatigue contextualized to activities of fixed intensity and duration, may also be measured. This study investigated the effects of a 15-month intervention on fatigue and fatigability in breast cancer survivors (BCS); explored the fatigue-fatigability relationship; and evaluated the impacts of fatigue and fatigability on anxiety, depression, sleep disturbance, and endocrine symptoms.MethodsA randomized controlled trial design was applied to an exercise program called BLESS (Better Life after cancer, Energy, Strength, and Support). The intervention included this 12-week exercise program and four follow-up contacts intended to promote exercise adherence over the following year. Participants were women aged 20 to 69 who had been diagnosed with stage I, II, or III breast cancer; had completed active treatment; and had moderate or higher fatigue. At the completion of the intervention, the survey responses of 40 BCS were evaluated using the chi-square test and multiple regression analysis. The Korean versions of the Revised Piper Fatigue Scale and Pittsburgh Fatigability Scale were used to measure fatigue and fatigability, respectively.ResultsThere was no significant difference in fatigue or fatigability between the experimental and control groups at intervention completion. However, the control group showed a stronger association than the experimental group between fatigue and physical fatigability. In the control group, fatigue and fatigability were significantly associated with anxiety, depression, sleep disturbance, and endocrine symptoms. In the experimental group, only the cognitive/mood fatigue score and depression were significantly associated. Only endocrine symptoms influenced mental fatigability (B = − 0.185, P < 0.05), and only depression influenced cognitive/mood fatigue (B = 1.469, P < 0.05).ConclusionsFatigue and fatigability showed different correlations with cancer-related symptoms after the exercise intervention. Future assessments of fatigability in intervention studies will allow measurement of the spectrum of patients’ abilities to overcome fatigue at various physical activity levels while capturing different aspects of cancer-related symptoms.Trial registrationThis study was retrospectively registered on Clinical Research Information Service (KCT0005763; date of registration: 31/12/2020).

Psychometric properties of the Korean version of the Pittsburgh Fatigability Scale in breast cancer survivors

BackgroundFatigability has recently emerged in oncology as a concept that anchors patients’ perceptions of fatigue to defined activities of specified duration and intensity. This study aimed to examine the psychometric properties of the Korean version of the Pittsburgh Fatigability Scale (K-PFS) for women with breast cancer.MethodsThis cross-sectional study involved 196 women with breast cancer recruited from a tertiary hospital in Seoul, Korea. Reliability was evaluated using Cronbach’s alpha, and confirmatory factor analysis was conducted to examine the factor structure of the K-PFS. Four goodness-of-fit values were evaluated: (1) the comparative fit index (CFI), (2) the Tucker–Lewis index (TLI), (3) the root mean square error of approximation (RMSEA), and (4) the standardized root mean square residual (SRMR).ResultsOf the 196 survivors, 71.1% had greater physical fatigability (K-PFS Physical score ≥ 15) and 52.6% had greater mental fatigability (K-PFS Mental score ≥ 13). The Cronbach’s alpha coefficient for the total K-PFS scale was 0.926, and the coefficients for the physical and mental fatigability domains were 0.870 and 0.864, respectively. In the confirmatory factor analysis for physical fatigability, the SRMR value (0.076) supported goodness of fit, but other model fit statistics did not (CFI = 0.888, TLI = 0.826, and RMSEA = 0.224). For mental fatigability, although three goodness-of-fit values were acceptable (CFI = 0.948, TLI = 0.919, and SRMR = 0.057), the RMSEA value (0.149) did not indicate good model fit. However, each item coefficient was statistically significant (> 0.5), and the K-PFS was therefore found to be valid from a theoretical perspective.ConclusionThis study provides meaningful information on the reliability and validity of the K-PFS instrument, which was developed to meet an important need in the context of breast cancer survivors. Additional research should examine its test–retest reliability and construct validity with performance measures.

Music-based therapy in rehabilitation of people with multiple sclerosis: a systematic review of clinical trials.

Multiple sclerosis (MS) is a major cause of chronic neurological disability in young adults. An increasing number of controlled studies have assessed the potential rehabilitative effects of new drug-free treatments, complementary to the standard care, including music-based therapy (MBT). To analyze the evidence for the effectiveness of MBT within the therapeutic approaches to individuals diagnosed with MS. A systematic review of clinical trials was performed with searches in the following databases: BIOSIS, CINAHL, Cochrane, EBSCO, ERIC, Google Scholar, IBECS, LILACS, LISA (ProQuest), Medline, PEDro, PsycINFO (APA), Psychological & Behavioral, PubMed, SciELO, Scopus, SPORTDiscus and Web of Science. Clinical trials comparing MBT versus conventional therapy/no intervention were included. From the 282 studies identified, 10 trials were selected. Among these, the total sample consisted of 429 individuals: 253 were allocated to the experimental group (MBT) and 176 to the control group (conventional therapies or no intervention). All the studies presented high methodological quality. Modalities of MBT were clustered into four groups: (1) Rhythmic auditory; (2) Playing musical instruments; (3) Dance strategy; and (4) Neurological music therapy. Overall, the studies consistently showed that MBT was better than conventional therapy or no intervention, with regard to gait parameters (double support time and walking speed), fatigue level, fatigability, coordination, dexterity, balance, walking endurance, lower extremity functional strength, emotional status and pain. Regarding mental fatigability and memory, the data were conflicting and the evidence was unclear. MBT is a safe and effective approach for clinical rehabilitation of MS patients that leads to positive results regarding both motor and non-motor functions.

Validation of the Traditional Chinese Version of the Pittsburgh Fatigability Scale for Older Adults

ABSTRACT Objectives The Pittsburgh Fatigability Scale (PFS) is a self-administered 10-item tool to measure physical and mental fatigability in older adults. The aim of the current study was to validate the psychometric properties of the traditional Chinese version of PFS (TC-PFS). Methods We recruited 114 community-dwellingolder adults, where 35 were diagnosed with late-life depression (LLD), 26 with mild cognitive impairment (MCI), and 53 were cognitively normal (CN) from a larger community study of older adults. Statistical analyses were done separately for TC-PFS Physical and Mental subscales. Factor analysis was used for reliability, Cronbach’s alpha for internal consistency, Pearson’s correlation for construct validity, and group comparison for discriminative validity. Results Factor analysis revealed a two-factor structure for both the TC-PFS Physical and Mental subscales with high reliability (α = 0.89 and 0.89, respectively). Patients with LLD had the highest PFS scores, with 80.0% and 82.9% classified as having greater physical and mental fatigability. For concurrent validity, we found moderate associations with the vitality and physical functioning subscales of the 36-Item Short Form Health Survey. For convergent validity, TC-PFS showed moderate association with emotional-related psychometrics, particularly for the Physical subscale in those with LLD. In contrast, TC-PFS Mental subscale showed correlations with cognitive function, particularly in the MCI group. Conclusions Our results indicate that the TC-PFS is a valid instrument to measure perceived physical and mental fatigability in older Taiwanese adults. Clinical implications: Perceived fatigability reflects the underlying physical, mental or cognitive function in older adults with or without depression.

Validation of Perceived Mental Fatigability Using the Pittsburgh Fatigability Scale.

Establish reliability, concurrent and convergent validity of the Pittsburgh Fatigability Scale (PFS) Mental subscale. Cross-sectional. Older adults from two University of Pittsburgh registries, Baltimore Longitudinal Study of Aging (BLSA), and Long Life Family Study (LLFS). PFS Mental subscale validation was conducted using three cohorts: (1) Development Sample (N = 664, 59.1% women, age 74.8 ± 6.4 years, PFS Mental scores 10.3 ± 9.1), (2) Validation Sample I-BLSA (N = 430, 51.9% women, age 74.5 ± 8.2 years, PFS Mental scores 9.4 ± 7.9), and (3) Validation Sample II-LLFS (N = 1,917, 54.5% women, age 72.2 ± 9.3 years, PFS Mental scores 7.5 ± 8.2). Development Sample, Validation Sample I-BLSA, and Validation Sample II-LLFS participants self-administered the 10-item Pittsburgh Fatigability Scale. Validation Sample II-LLFS completed cognition measures (Trail Making Tests A and B), depressive symptomatology (Center for Epidemiologic Studies-Depression Scale, CES-D), and global fatigue from two CES-D items. In the Development Sample and Validation Sample I-BLSA, confirmatory factor analysis showed all 10 items loaded on two factors: social and physical activities (fit indices: SRMSR = 0.064, RMSEA = 0.095, CFI = 0.91). PFS Mental scores had strong internal consistency (Cronbach's α = 0.85) and good test-retest reliability (ICC = 0.78). Validation Sample II-LLFS PFS Mental scores demonstrated moderate concurrent and construct validity using Pearson (r) or Spearman (ρ) correlations against measures of cognition (Trail Making Tests A (r = 0.14) and B (r = 0.17) time), depressive symptoms (r = 0.31), and global fatigue (ρ = 0.21). Additionally, the PFS Mental subscale had strong convergent validity, discriminating according to established clinical or cognitive testing cut points, with differences in PFS Mental scores ranging from 3.9 to 7.6 points (all P < .001). All analyses were adjusted for family relatedness, field center, age, sex, and education. The validated PFS Mental subscale may be used in clinical and research settings as a sensitive, one-page self-administered tool of perceived mental fatigability in older adults.

Fatigue in men and women who have returned to work after stroke: Assessed with the Fatigue Severity Scale and Mental Fatigue Scale.

ObjectiveTo assess the occurrence of self-reported fatigue among men and women who have returned to work after stroke, and the association between 2 fatigue rating scales.DesignA cross-sectional study.SubjectsA total of 91 adults (58 men/33 women, mean age 53 years) with mild to moderate disability. Methods: Questionnaires were posted to participants approximately one year after stroke. Fatigue was assessed with the Fatigue Severity Scale (FSS) and the Mental Fatigue Scale (MFS).ResultsIn total, 58% of the women and 33% of the men reported fatigue on the FSS (total score ≥ 4), and 46% of the women and 28% of the men reported mental fatigue on the MFS (total score ≥ 10.5). Being easily fatigued, decreased motivation, mental fatigability and sensitivity to stress were the most reported problems. FSS and MFS were moderately associated (rho 0.517–0.732).ConclusionFatigue is common among persons who have returned to work after stroke, and interferes with daily life. The long-term consequences of fatigue should be addressed after stroke, especially in women. The FSS and the MFS can be used in combination, as they provide information on different aspects of fatigue.LAY ABSTRACTFatigue can be a long-lasting and disabling impairment following stroke. There is a need for increased knowledge of how fatigue affects people who have returned to work after stroke, and which fatigue rating scales capture their problems most appropriately. The aim of this study was to assess the occurrence of self-reported fatigue among men and women who have returned to work after stroke, and to determine the association between 2 fatigue rating scales. The study was based on a postal survey and includes 91 participants. Fatigue was found to be common 1 year after stroke, especially in women, and interfered with daily life. The 2 fatigue rating scales could be used in combination, as they provide different information on fatigue. The findings could be used to develop support that enables people with stroke to return to and to stay at work long-term.

Relationship Between Perceived Physical and Mental Fatigability and Physical Performance in Very Old Adults

To investigate the relationship between perceived physical and mental fatigability and physical performance in community-dwelling very old adults (≥80 years). We examined the association in one retired community in Beijing including 404 very old adults. Pittsburgh Fatigability Scale (PFS), Chinese version, was used to assess perceived fatigability in physical domain (PFS-P) and mental domain (PFS-M). High fatigability is defined as PFS-P ≥ 15, and PFS-M ≥ 13. Physical performance measures include grip strength, usual gait speed, chair stand and Short Physical Performance Battery (SPPB) test. Women have higher PFS scores (both PFS-P & PFS-M) and higher prevalence of high fatigability than men. After adjusting for sex, usual gait speed and SPPB scores were significantly associated with PFS-P & PFS-M, while grip strength and chair stand performance were significantly associated with PFS-P only. After multivariable adjustment, usual gait speed (B=-3.745, P=0.021) and chair stand performance (B=0.335, P=0.005) were significantly associated with PFS-P, while usual gait speed (B=-2.656, P=0.006) and SPPB scores (B=-0.214, P=0.029) were significantly associated with PFS-M. Perceived physical and mental fatigability is highly prevalent in very older adults and they differ by sex. The significant associations between PFS scores and performance measures suggest that PFS is of potential clinical importance, especially when testing performance measures are not feasible. Utilization of PFS score can assist in identifying target populations who are at risk of reduced physical functions, such as older with depression, older women. Interventions to improve usual gait speed are likely to reduce both perceived physical and mental fatigability.

More Energy and Less Fatigue: Implications for Successful Brain Aging

Higher energy and lower fatigue are intuitively important to live independent, active lives. However, little is known about the relation between brain health, energy, and fatigue in older adults. From a neurobiological standpoint, energy and fatigue appear to rely on distinct, albeit overlapping brain networks, but most evidence is from patients with neurodegenerative conditions. These relations have not been fully examined in community older adults. In this symposium, we first present an overview of the neurobiology underlying fatigability and energy states. We will then present original unpublished data on brain health, fatigability, and energy from four well-established epidemiological studies of aging: Osteoporotic Fractures in Men Study (MrOS), Long Life Family Study (LLFS), Baltimore Longitudinal Study of Aging (BLSA), and the Health Aging Body Composition Study (Health ABC). Specifically, Ms. Allen will explore whether personality traits are related to perceived mental fatigability in MrOS. Using LLFS data, Ms. Gmelin will examine whether perceived physical fatigability is associated with global cognition, verbal fluency, memory and psychomotor speed. Dr. Schrack will share BLSA data showing cross-sectional and longitudinal associations between lower walking efficiency and reduced brain volumes. Dr. Tian will evaluate the neuroimaging signature of perceived energy levels in Health ABC. Taken together, our data indicate that higher energy and lower fatigability likely reflect overlapping but distinct aspects of brain health. The long-term effects of promoting energy and lowering fatigability on dementia should be further studied.

The Relationship Between Personality and Perceived Mental Fatigability

Several personality traits are known to be protective against global fatigue, however perceived mental fatigability (PMF, Pittsburgh Fatigability Scale 0-50) specifically measures an individual’s susceptibility to cognitive tiredness and is associated with mobility decline. We assessed whether optimism, conscientiousness, goal reengagement and goal disengagement contributed to greater PMF in 1,812 men (mean±SD age 84.4±4.2 years, 90.4% white) in the Osteoporotic Fractures in Men Study 4th visit (2014-2016). Covariates included demographic, psychological/behavioral factors, health conditions, physical activity and function. Prevalence of higher PMF (score ≥13) was 25% (n=448). In a covariate-adjusted regression model, each SD lower conscientiousness and lower optimism were associated with 0.93 and 0.61 SDs greater PMF, each p<0.01. Goal disengagement and goal reengagement were not associated with PMF. These findings warrant further investigation into how personality traits may help clinicians design targeted and effective interventions to reduce fatigability, and consequently lower the risk of adverse aging-related health outcomes.

Neuroimaging markers of chronic fatigue in older people: a narrative review.

Chronic fatigue is a common symptom in older adults. Although some studies have attempted to identify the neuronal correlates of fatigue associated with chronic diseases, the scientific evidence is scarce regarding fatigue in older people not suffering from a specific disease. To gather available evidence of neuroimaging studies investigating the associations between fatigue and brain health in older adults out of the context of a specific disease, and to identify potential brain structures associated with this symptom. Studies considering exclusively patients with a specific disease and/or studies focusing on physiological mechanisms of acute fatigue induced by the realization of cognitive and physical tasks were excluded. Very few studies on the associations of fatigue with neuroimaging markers are currently available. Fatigue was associated with reduced hippocampus volumes and with hippocampal amyloid deposition. Regarding the association between fatigue and the circuit of basal ganglia, putamen and thalamus were associated with physical fatigability, whereas amygdala and thalamus with mental fatigability. Very limited evidence about white matter integrity found that healthy individuals with high levels of fatigue had a greater total volume of leukoaraiosis. This review suggests that hippocampus damage and potentially loss of function in basal ganglia networks could play a role on chronic fatigue during aging. Further studies are needed to assess the associations of fatigue with white matter alterations.

Effects of old age on fatigability and sensorimotor characteristics of a repetitive upper limb fatiguing task.

Objectives1) Determine the effects of old age on sensorimotor responses to a fatiguing work-like task. 2) Explore how old age influences the relationships between task fatigability, everyday perceptions of fatigability, and sensorimotor function.MethodsHealthy young (N = 17, 9W) and older (N = 13, 10W) adults completed the Pittsburgh Fatigability Scale to assess everyday perceptions of physical (PF) and mental fatigability and performed a repetitive tapping task to fatigue. Before and after the task, grip strength was assessed using a hand-grip dynamometer and touch-pressure sensitivity was measured (shoulder, hand) using Semmes-Weinstein monofilaments.ResultsOlder, but not young adults, had increased touch-pressure sensitivity at the shoulder after fatigue (interaction, p = 0.007). No changes in grip strength were observed (p>0.05). Task fatigability was not different between young and old adults (p>0.05). Having less task fatigability was associated with lower PF, higher grip strength, and higher touch-pressure sensitivity at the hand (ρ = 0.37–0.58, p<0.05), with the hand sensation association also observed in the old adult subgroup (ρ = 0.56, p = 0.046).ConclusionsWith old age, there were fatigue-related alterations to sensory but not physical function. While task fatigability was associated with perceptual, physical, and sensory features, sensory features appear to have a more important role with old age.

The Associations of Activity Fragmentation With Physical and Mental Fatigability Among Community-Dwelling 75-, 80-, and 85-Year-Old People.

Fatigue related to task standardized by duration and intensity, termed fatigability, could manifest as shortening of activity bouts throughout the day causing daily activity to accumulate in a more fragmented pattern. Our purpose was to study the association of activity fragmentation with physical and mental dimensions of fatigability. A cross-sectional study of 485 community-dwelling 75-, 80-, and 85-year-old people using a thigh-worn accelerometer for 3-7 days. Activity fragmentation was studied as Active-to-Sedentary Transition Probability for 2 operational definitions of physical activity: accelerations equivalent to at least light physical activity and for upright posture. Physical fatigability was assessed as perceived exertion fatigability, performance fatigability severity, and with the Physical Fatigue Subscale of the Situational Fatigue Scale. Mental fatigability was assessed with the Mental Fatigue Subscale of the Situational Fatigue Scale and as a decrease in perceived mental alertness after a 6-minute walk test. Higher activity fragmentation was associated with higher self-reported physical fatigability, perceived exertion fatigability, and performance fatigability severity, independent of total activity minutes (β = 0.13-0.33, p < .05 for all). Higher activity fragmentation was not associated with mental fatigability in the fully adjusted models. The associations with fatigability indices were similar for both activity fragmentation indicators. Associations of activity fragmentation and performance fatigability severity were similar also among those with the highest intensity-based physical activity volume. The findings provide support that studying fragmented activity patterns can be useful in identifying those at risk for high fatigability, even among those with relatively high physical activity level.

Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial.

BackgroundFatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue.MethodThis study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60–19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight <50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose.ResultsAmong 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p < .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI −1.8 to 2.1; p = .88), or mental fatigability (−1.0; 95% CI −2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI −3.6 to 2.8, p = .79) and −2.2 (95% CI −8.8 to 4.5, p = .51).ConclusionsLevothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability.

Associations of Actigraphic Sleep Parameters With Fatigability in Older Adults.

Poor sleep may increase the likelihood of fatigue, and both are common in later life. However, prior studies of the sleep-fatigue relationship used subjective measures or were conducted in clinical populations; thus, the nature of this association in healthier community-dwelling older adults remains unclear. We studied the association of actigraphic sleep parameters with perceived fatigability-fatigue in response to a standardized task-and with conventional fatigue symptoms of low energy or tiredness. We studied 382 cognitively normal participants in the Baltimore Longitudinal Study of Aging (aged 73.1 ± 10.3 years, 53.1% women) who completed 6.7 ± 0.9 days of wrist actigraphy and a perceived fatigability assessment, including rating of perceived exertion (RPE) after a 5-minute treadmill walk or the Pittsburgh Fatigability Scale (PFS). Participants also reported non-standardized symptoms of fatigue. After adjustment for age, sex, race, height, weight, comorbidity index, and depressive symptoms, shorter total sleep time (TST; <6.3 hours vs intermediate TST ≥6.3 to 7.2 hours) was associated with high RPE fatigability (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.29, 5.06, p = .007), high PFS physical (OR = 1.88, 95% CI = 1.04, 3.38, p = .035), and high mental fatigability (OR = 2.15, 95% CI = 1.02, 4.50, p = .044), whereas longer TST was also associated with high mental fatigability (OR = 2.19, 95% CI = 1.02, 4.71, p = .043). Additionally, longer wake bout length was associated with high RPE fatigability (OR = 1.53, 95% CI = 1.14, 2.07, p = .005), and greater wake after sleep onset was associated with high mental fatigability (OR = 1.14, 95% CI = 1.01, 1.28, p = .036). Among well-functioning older adults, abnormal sleep duration and sleep fragmentation are associated with greater perceived fatigability.

PREVALENCE AND HERITABILITY OF PERCEIVED MENTAL FATIGABILITY IN THE LONG LIFE FAMILY STUDY

We examined the prevalence and heritability of perceived mental fatigability among older adults enrolled in the Long Life Family Study. Participants (N=2342; 55% female) self-administered the Pittsburgh Fatigability Scale (PFS; scores range 0-50; higher score=greater fatigability). Using the PFS mental subscale, we evaluated differences across age strata (adjusted for family structure and field center) and estimated genetic heritability using the variance covariance methods implemented in SOLAR to determine genetic heritability (adjusted for age, sex, and field center). PFS mental score (mean±SD) and prevalence of higher mental fatigability (PFS ≥13) was greater across age strata: 60-69 (N=996, 5.9± 6.5, 14.5%), 70-79 (N=830, 6.8 ±7.6, 18.7%), 80-89 (N=251, 11.7±10.8, 41.8%), and ≥90 (N=265, 20.2±13.6, 67.2%), p<0.0001. Only among those ≥90, females (21.7±13.5) had greater mental fatigability than males (18.0±13.5), p=0.03. Residual heritability of mental fatigability was 0.17, p<0.0001. Future analyses will evaluate correlates of mental fatigability to identify potential avenues for intervention.

ROLE OF COPING STYLES AND NEGATIVE LIFE EVENTS ON HIGHER PERCEIVED MENTAL FATIGABILITY IN OLDER ADULTS

Older adults are vulnerable to negative recent life events (RLE) which deplete attentional resources and leads to cognitive exhaustion. Adaptive coping styles reduce perceived stress severity but their role on cognitive tiredness is unknown. We examined RLE and coping styles on perceived mental fatigability (Pittsburgh Fatigability Scale (PFS), 0-50pts, higher=greater fatigability) in the Long Life Family Study (N=1464, age=74.7±12.6, female=57.7%, 43.9% ≥1 major RLE past 6 months, 27.8% higher mental fatigability≥13). All analyses adjusted for family structure, field center, age, and sex. PFS mental scores correlated with all NEO-FFI (60-item, 5-domain) personality traits representing maladaptive (neuroticism r=0.25 p<.0001) and adaptive (conscientiousness r=-0.18, extraversion r=-0.24, p<.00001) coping. Having ≥1RLE was associated with higher mental fatigability (OR=1.4, 95% CI:1.2,1.8, p=.0004); adjustment for neuroticism (OR=1.3, 95% CI:0.9,1.7, p=.06) attenuated the association. Education on adaptive coping may be a modifiable skill that allows older adults to maintain lower perceived mental fatigability despite stressful events.

PERCEIVED MENTAL FATIGABILITY: NOVEL INSIGHTS INTO SOCIOBEHAVIORAL CORRELATES AND HERITABILITY

Fatigue, a common patient-reported outcome, is a unique risk factor associated with both cognitive and physical function. Perceived mental fatigability, a self-report measure of cognitive fatigue anchored to activities of fixed intensity and duration, eliminates self-pacing bias, and therefore is a more sensitive measure of the degree to which cognitive tiredness limits activity. Higher perceived mental fatigability has been associated with functional decline and lower grey matter brain volumes in older adults. We developed the Pittsburgh Fatigability Scale (PFS), a self-administered, 10-item tool to assess perceived physical and mental fatigability across a range of activities, which is widely used internationally. We previously validated the PFS physical subscale. Using a large multicenter international cohort, the Long Life Family Study, we will present the validation of the PFS mental subscale, examine its epidemiology, and explore genetic and socio-behavioral factors associated with perceived mental fatigability in older adults. Specifically, Ms. Renner will share the results of the validation of the PFS mental subscale; Ms. Meinhardt will present heritability and prevalence of higher perceived mental fatigability across age strata and sex; and Ms. Gmelin will consider the link between stress and coping styles on perceived mental fatigability. Further, using a smaller methodological study, the Developmental Epidemiologic Cohort Study, Ms. Graves will explore whether diurnal patterns of physical activity using accelerometry differ in older adults with higher versus lower perceived mental fatigability. Dr. Simonisick, our Discussant, will critically review the presentations and share future directions to inform potential interventions aimed at lowering perceived mental fatigability.