MoCA Intraindividual Cognitive Variability in Older Adults With Type 1 Diabetes.

Older adults with type 1 diabetes (T1D) may have an elevated risk of developing Alzheimer disease and related dementia. Higher intraindividual cognitive variability (IICV) has been proposed as a novel risk factor of Alzheimer disease and related dementia. Here, we examined the association between cross-domain IICV measured using the Montreal Cognitive Assessment (MoCA) and cognitive impairment measured using traditional neuropsychological tests in older individuals with T1D. Participants with T1D (N=201) completed both the MoCA and a battery of traditional neuropsychological tests. Participants with cognitive impairment, determined using traditional tests, had significantly higher IICV scores and significantly lower total MoCA scores ( P <0.001). However, the effect of the total score was greater than that of the IICV score on the likelihood of cognitive impairment (total odds ratio=3.50, IICV odds ratio=2.03, P <0.001). The MoCA total score performed better than the MoCA IICV score in identifying T1D individuals classified with cognitive impairment.

Ecological Momentary Assessment of Cognition in Clinical and Community Samples: Reliability and Validity Study.

BACKGROUND: The current methods of evaluating cognitive functioning typically rely on a single time point to assess and characterize an individual's performance. However, cognitive functioning fluctuates within individuals over time in relation to environmental, psychological, and physiological contexts. This limits the generalizability and diagnostic utility of single time point assessments, particularly among individuals who may exhibit large variations in cognition depending on physiological or psychological context (eg, those with type 1 diabetes [T1D], who may have fluctuating glucose concentrations throughout the day). OBJECTIVE: We aimed to report the reliability and validity of cognitive ecological momentary assessment (EMA) as a method for understanding between-person differences and capturing within-person variation in cognition over time in a community sample and sample of adults with T1D. METHODS: Cognitive performance was measured 3 times a day for 15 days in the sample of adults with T1D (n=198, recruited through endocrinology clinics) and for 10 days in the community sample (n=128, recruited from TestMyBrain, a web-based citizen science platform) using ultrabrief cognitive tests developed for cognitive EMA. Our cognitive EMA platform allowed for remote, automated assessment in participants' natural environments, enabling the measurement of within-person cognitive variation without the burden of repeated laboratory or clinic visits. This allowed us to evaluate reliability and validity in samples that differed in their expected degree of cognitive variability as well as the method of recruitment. RESULTS: The results demonstrate excellent between-person reliability (ranging from 0.95 to 0.99) and construct validity of cognitive EMA in both the sample of adults with T1D and community sample. Within-person reliability in both samples (ranging from 0.20 to 0.80) was comparable with that observed in previous studies in healthy older adults. As expected, the full-length baseline and EMA versions of TestMyBrain tests correlated highly with one another and loaded together on the expected cognitive domains when using exploratory factor analysis. Interruptions had higher negative impacts on accuracy-based outcomes (ß=-.34 to -.26; all P values <.001) than on reaction time-based outcomes (ß=-.07 to -.02; P<.001 to P=.40). CONCLUSIONS: We demonstrated that ultrabrief mobile assessments are both reliable and valid across 2 very different clinic versus community samples, despite the conditions in which cognitive EMAs are administered, which are often associated with more noise and variability. The psychometric characteristics described here should be leveraged appropriately depending on the goals of the cognitive assessment (eg, diagnostic vs everyday functioning) and the population being studied.

Usefulness of the Montreal Cognitive Assessment in Older Adults With Type 1 Diabetes.

Objective: Older adults with type 1 diabetes are at high risk for cognitive impairment, yet the usefulness of common cognitive screening instruments has not been evaluated in this population. Methods: A total of 201 adults ≥60 years of age with type 1 diabetes completed a battery of neuropsychological measures and the Montreal Cognitive Assessment (MoCA). Receiver operating characteristic (ROC) curves and Youden indices were used to evaluate overall screening test performance and to select an optimal MoCA cutoff score for detecting low cognitive performance, as defined as two or more neuropsychological test performances ≥1.5 SD below demographically corrected normative data. Results: The ROC area under the curve (AUC) was 0.745 (P < 0.001). The publisher-recommended cutoff score of <26 resulted in sensitivity of 60.4% and specificity of 71.4%, whereas a cutoff score of <27 resulted in sensitivity of 75.0% and specificity of 61.0%. The Youden indices for these cutoff scores were 0.318 and 0.360, respectively. Minimally acceptable sensitivity (i.e., >0.80) was obtained when using a cutoff score of <28, whereas >0.80 specificity was obtained with a cutoff score of <25. Conclusions: The MoCA has modest overall performance (AUC 0.745) as a cognitive screening instrument in older adults with type 1 diabetes. The standard cutoff score of <26/30 may not adequately detect individuals with neuropsychological testing-defined abnormal cognition. The optimal MoCA cutoff score (based on the Youden index) was <27/30. A score of <28 resulted in acceptable sensitivity but was accompanied by low specificity (42%). Future studies with a more diverse population are needed to confirm these findings.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Depressive symptoms and suicidality among individuals with epilepsy enrolled in self-management studies: Results from the US Centers for Disease Control and Prevention Managing Epilepsy Well (MEW) Network.

Depression is a common comorbidity in people with epilepsy (PWE) that negatively affects self-management and a variety of health outcomes. Suicidal ideation is also more common among PWE than the general population. We examined correlates of depressive symptoms and suicidal ideation in adults using pooled data from epilepsy self-management studies conducted by sites in the Centers for Disease Control and Prevention (CDC) Research Center's Managing Epilepsy Well (MEW) Network that assessed depression severity with the 9-item Patient Health Questionnaire (PHQ-9). Of the 770 subjects in the analysis (mean age 42.4 ±â€¯13.0 years), the mean total PHQ-9 score was 9.4 ±â€¯6.6 and 334 subjects (43.4%) had moderate to severe depressive symptoms (PHQ-9 ≥ 10). Only ongoing seizures and low education were associated with moderate-severe depressive symptoms in multiple logistic regression analysis. Suicidality (PHQ-9, item 9 score ≥ 1) was endorsed by 155 subjects (20.1%). Only nonsuicidal depressive symptoms were associated with suicidality in multiple variable logistic regression analysis. We show in this large and regionally diverse dataset that both depression and suicidal ideation are common among PWE enrolled in self-management studies. Future studies are needed to examine whether suicidality exists independently of other depressive symptoms in some populations with epilepsy and investigate other correlates of suicidality that may inform screening practices.

The relationship between neuropsychological assessment, numeracy, and functional status in older adults with type 1 diabetes.

While data are accumulating on the association between neuropsychological performance and real-world endpoints, less is known about the association with medical self-management skills. The self-management of type 1 diabetes (T1D) is often complex, and mismanagement can result in hypoglycaemia and hyperglycaemia and associated morbidity and mortality. The T1D Exchange conducted a case-control study evaluating factors associated with severe hypoglycaemia in older adults (≥ 60 years old) with longstanding T1D (≥ 20 years). A battery of neuropsychological and functional assessments was administered, including measures of diabetes-specific self-management skill (diabetes numeracy) and instrumental activities of daily living (IADL). After adjusting for confounding variables, diabetes numeracy was related to memory and complex speeded attention; while IADL were associated with simple processing speed, executive functioning, complex speeded attention and dominant hand dexterity. The severity of overall cognitive deficit was uniquely associated with both diabetes numeracy and IADL, when controlling for age, education, frailty and depression. This study demonstrates that the cognitive deficits in older adults with T1D have functional implications for both diabetes management and IADL. Further research is needed to determine specific interventions to maximise diabetes self-management in older adults with declining cognition.

Medication Intervention for Chronic Kidney Disease Patients Transitioning from Hospital to Home: Study Design and Baseline Characteristics.

BACKGROUND: The hospital readmission rate in the population with chronic kidney disease (CKD) is high and strategies to reduce this risk are urgently needed. METHODS: The CKD-Medication Intervention Trial (CKD-MIT; www.clinicaltrials.gov; NCTO1459770) is a single-blind (investigators), randomized, clinical trial conducted at Providence Health Care in Spokane, Washington. Study participants are hospitalized patients with CKD stages 3-5 (not treated with kidney replacement therapy) and acute illness. The study intervention is a pharmacist-led, home-based, medication management intervention delivered within 7 days after hospital discharge. The primary outcome is a composite of hospital readmissions and visits to emergency departments and urgent care centers for 90 days following hospital discharge. Secondary outcomes are achievements of guideline-based targets for CKD risk factors and complications. RESULTS: Enrollment began in February 2012 and ended in May 2015. At baseline, the age of participants was 69 ± 11 years (mean ± SD), 50% (77 of 155) were women, 83% (117 of 141) had hypertension and 56% (79 of 141) had diabetes. At baseline, the estimated glomerular filtration rate was 41 ± 14 ml/min/1.73 m2 and urine albumin-to-creatinine ratio was 43 mg/g (interquartile range 8-528 mg/g). The most frequent diagnosis category for the index hospital admission was cardiovascular diseases at 34% (53 of 155), but the most common single diagnosis for admission was community-acquired acute kidney injury at 10% (16 of 155). CONCLUSION: Participants in CKD-MIT are typical of acutely ill hospitalized patients with CKD. A medication management intervention after hospital discharge is under study to reduce post-hospitalization acute care utilization and to improve CKD management.

Association Between Prescription Opioid Use and Biomarkers of Kidney Disease in US Adults.

BACKGROUND/AIMS: Prescription opioid use is increasing despite concerns about drug safety. We examined relationships between use of analgesics with biomarkers of chronic kidney disease (CKD) in a representative sample of adults in the United States (US). METHODS: Participants (n=3980) were from the National Health and Nutrition Examination Survey (NHANES) 2009-2010. Use of any analgesic, prescription opioids, and NSAIDs were compared to referent groups with use of non-analgesic prescription medication or use of no prescription medication. CKD biomarkers including urine albumin-to-creatinine ratio (UACR) and serum-creatinine-based estimated glomerular filtration rate (eGFR; CKD Epidemiology Collaboration: CKD-EPI equation) were analyzed as continuous and binary variables (UACR ≥30 mg/g or eGFR <60 mL/min per 1.73m2; median splits). RESULTS: Frequencies of use were: any prescription analgesic 12.7% (507/3980); prescription opioids 5.1% (204/3980); NSAIDs 5.6% (224/3980); non-analgesic medication 38.7% (1540/3980); no medication 48.6% (1933/3980). Prescription analgesic use (ß=0.17, p=0.021) and opioid use (ß=0.19, p=0.002) were associated with higher UACR values, while NSAID use was not (ß=0.17, p=0.105). Prescription analgesic use was related to UACR ≥5.98 mg/g (median), (OR=1.34, 95%CI=1.01-7.79, p=0.045). No type of analgesic use was related to CKD-EPI eGFR. CONCLUSION: In a representative US population, prescription opioid use associated with higher albuminuria levels compared to non-opioid-users.

Cognition in Adults and Older Adults With Type 1 Diabetes: Chicken or Egg?

IN BRIEF Cognitive impairment and cognitive decline are common in adults with type 1 diabetes. Although several diabetes-related variables have been associated with cognitive functioning in both cross-sectional and longitudinal studies, inconsistencies remain. This is particularly true in older adults. Cognitive impairment appears to be both a consequence of and a risk factor for poor diabetes self-management and associated glycemic outcomes. Interventions such as cognitive compensatory strategies, assistive technology, and simplified treatment regimens may limit the impact of cognitive impairment on self-management in adults and older adults with type 1 diabetes.

PACES in epilepsy: Results of a self-management randomized controlled trial.

OBJECTIVE: Self-management challenges facing adults with epilepsy include limited understanding of the condition and treatment, associated psychosocial issues, and lack of community integration. Self-management interventions improve patients' medical, life role, and emotional management. Previous interventions, developed from expert opinion, indicated issues with participant engagement/retention, and limited follow-up periods. PACES in Epilepsy addressed methodologic concerns by utilizing patient needs assessment data (n = 165) to derive self-management content and program features for evaluation via randomized controlled trial (RCT). METHODS: Participants were adults with chronic epilepsy (n = 83), without serious mental illness or substantive intellectual impairment, who were recruited from two epilepsy centers. Participants were assigned randomly to intervention or treatment-as-usual groups. Outcomes included the Epilepsy Self-Management Scale (ESMS), Epilepsy Self-Efficacy Scale (ESES), Quality of Life in Epilepsy-31 (QOLIE-31), Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7), administered at baseline, postintervention (8 weeks), and 6 months postintervention. The intervention was an 8-week group of 6-8 adults co-led by a psychologist and trained peer with epilepsy that met one evening per week at a hospital for 75 min. Topics included medical, psychosocial, cognitive, and self-management aspects of epilepsy, in addition to community integration and optimizing epilepsy-related communication. The treatment group provided satisfaction ratings regarding program features. RESULTS: PACES participants (n = 38) improved relative to controls (n = 40) on the ESMS (p < 0.001) and subscales [Information (p < 0.001); Lifestyle (p < 0.002)]; ESES (p < 0.001); and QOLIE-31 (p = 0.002). At 6-month follow up, PACES participants remained improved on the ESMS (p = 0.004) and Information subscale (p = 0.009); and Energy/Fatigue (p = 0.032) and Medication Effects (p = 0.005) of the QOLIE-31. Attrition in both groups was low (8% in each group) and all program satisfaction ratings exceeded 4.0/5.0, with leadership (4.76), topics (4.53), and location (4.30) as the most highly rated aspects. SIGNIFICANCE: A consumer generated epilepsy self-management program appears to be a promising intervention from multiple perspectives, particularly in relation to disability management.

Budget Impact Tool for Implementing Contingency Management for Co-occurring Alcohol Use Disorders and Serious Mental Illness.

OBJECTIVE: Contingency management (CM) is a behavioral intervention in which tangible incentives are provided to patients when they achieve a desired behavior (e.g., reducing or abstaining from alcohol use). The authors sought to describe the resource requirements and associated costs of various CM versions (usual, high magnitude, and shaping) tailored to a high-risk population with co-occurring serious mental illness and severe alcohol use disorder. METHODS: A microcosting analysis was conducted to identify the resource requirements of the different CM versions. This approach included semistructured interviews with site investigators, who also staffed the intervention. The resource costing method-multiplying the number of units of each resource utilized by its respective unit cost-was used to value the resources from a provider's perspective. All cost estimates were calculated in 2021 U.S. dollars. RESULTS: The cost of setting up a CM program was $6,038 per site. Assuming full capacity and 56% of urine samples meeting the requirement for receipt of the CM incentive, the average cost of 16 weeks of usual and shaping CM treatments was $1,119-$1,136 and of high-magnitude CM was $1,848-$1,865 per participant. CONCLUSIONS: A customizable tool was created to estimate the costs associated with various levels of treatment success and CM design features. After the trial, the tool will be updated and used to finalize per-participant cost for incorporation into a comprehensive economic evaluation. This costing tool will help a growing number of treatment providers who are interested in implementing CM with budgeting for and sustaining CM in their practices.

Mid-life sleep is associated with cognitive performance later in life in aging American Indians: data from the Strong Heart Study.

Background: Sleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to characterize, for the first time, the associations between sleep characteristics and subsequent cognitive performance in a sample of aging American Indians. Methods: We performed analyses on data collected in two ancillary studies from the Strong Heart Study, which occurred approximately 10 years apart with an overlapping sample of 160 American Indians (mean age at follow-up 73.1, standard deviation 5.6; 69.3% female and 80% with high school completion). Sleep measures were derived by polysomnography and self-reported questionnaires, including sleep timing and duration, sleep latency, sleep stages, indices of sleep-disordered breathing, and self-report assessments of poor sleep and daytime sleepiness. Cognitive assessment included measures of general cognition, processing speed, episodic verbal learning, short and long-delay recall, recognition, and phonemic fluency. We performed correlation analyses between sleep and cognitive measures. For correlated variables, we conducted separate linear regressions. We analyzed the degree to which cognitive impairment, defined as more than 1.5 standard deviations below the average Modified Mini Mental State Test score, is predicted by sleep characteristics. All regression analyses were adjusted for age, sex, years of education, body mass index, study site, depressive symptoms score, difference in age from baseline to follow-up, alcohol use, and presence of APOE e4 allele. Results: We found that objective sleep characteristics measured by polysomnography, but not subjective sleep characteristics, were associated with cognitive performance approximately 10 years later. Longer sleep latency was associated with worse phonemic fluency (ß = -0.069, p = 0.019) and increased likelihood of being classified in the cognitive impairment group later in life (odds ratio 1.037, p = 0.004). Longer duration with oxygen saturation < 90% was associated with better immediate verbal memory, and higher oxygen saturation with worse total learning, short and long-delay recall, and processing speed. Conclusion: In a sample of American Indians, sleep characteristics in midlife were correlated with cognitive performance a decade later. Sleep disorders may be modifiable risk factors for cognitive impairment and dementia later in life, and suitable candidates for interventions aimed at preventing neurodegenerative disease development and progression.

Barriers and Facilitators of Self-Management in Older People with Type 1 Diabetes: A Narrative Review Focusing on Cognitive Impairment.

Over the past decades, life expectancy of people with type 1 diabetes has increased considerably, which brings potential challenges due to the process of aging. Cognitive aging and dementia, as well as reductions in visual acuity, hearing and dexterity, can influence the frequency and quality of daily self-management activities, including medication taking and insulin dosing, glucose self-monitoring, and healthy eating. This can increase the risk for hypo- and hyperglycemic events, which, in turn, may contribute to cognitive decline. Because there is a gap in understanding the barriers and facilitators of self-management in older adults with type 1 diabetes and the relationship to cognitive functioning, the authors 1) review the available literature on cognitive aging and type 1 diabetes, 2) describe what self-management in later adulthood entails and the cognitive functions required for effective self-management behaviors, 3) analyze the interaction between type 1 diabetes, cognition, aging, and self-management behaviors, and 4) describe the barriers and facilitators for self-management throughout the life span and how they may differ for older people. Potential evidence-based practices that could be developed for older adults with type 1 diabetes are discussed. There is need for further studies that clarify the impact of aging on T1D self-management, ultimately to improve diabetes care and quality of life.

Risk factors associated with cognitive performance and cognitive impairment in older adults with type 1 diabetes: Data from the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) study.

BACKGROUND: Adults with type 1 diabetes (T1D) are considered at increased risk for cognitive impairment and accelerated brain aging. However, longitudinal data on cognitive impairment and dementia in this population are scarce. OBJECTIVE: To identify risk factors associated with cognitive performance and cognitive impairment in a longitudinal sample of older adults with T1D. METHODS: We analyzed data collected as part of the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) Study, in which 22 endocrinology practices participated. Randomized participants with T1D ≥60 years of age who completed at least one cognitive assessment were included in this study (n = 203). Cognitive impairment was classified using published recommendations. RESULTS: Older age, male sex, non-private health insurance, worse daily functioning, diagnosis of neuropathy, and longer duration of diabetes were associated with worse cognitive performance, but not cognitive impairment. 49 % and 39 % of the sample met criteria for cognitive impairment at baseline and 52 weeks respectively. Of the participants that had data at both time points, 10 % were normal at baseline and impaired at 52 weeks and 22 % of participants (44 % of those classified with cognitive impairment at baseline) reverted to normal over 52 weeks. CONCLUSION: This study indicated that several demographic and clinical characteristics are associated with worse cognitive performance in older adults with T1D, but there were no associations between these characteristics and cognitive impairment defined by NIH Toolbox cognitive impairment criteria. Caution is warranted when assessing cognition in older adults with T1D, as a large percentage of those identified as having cognitive impairment at baseline reverted to normal after 52 weeks. There is need for future studies on the interrelationship of cognition and aging to better understand the effects of T1D on cognitive health, to improve clinical monitoring and help mitigate the risk of dementia in this population.

Plasma Biomarkers of Brain Injury and Their Association With Brain MRI and Cognition in Type 1 Diabetes.

OBJECTIVE: To evaluate associations between plasma biomarkers of brain injury and MRI and cognitive measures in participants with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. RESEARCH DESIGN AND METHODS: Plasma amyloid-ß-40, amyloid-ß-42, neurofilament light chain (NfL), phosphorylated Tau-181 (pTau-181), and glial fibrillary acidic protein (GFAP) were measured in 373 adults who participated in the DCCT/EDIC study. MRI assessments included total brain and white matter hyperintensity volumes, white matter mean fractional anisotropy, and indices of Alzheimer disease (AD)-like atrophy and predicted brain age. Cognitive measures included memory and psychomotor and mental efficiency tests and assessments of cognitive impairment. RESULTS: Participants were 60 (range 44-74) years old with 38 (30-51) years' T1D duration. Higher NfL was associated with an increase in predicted brain age (0.51 years per 20% increase in NfL; P < 0.001) and a 19.5% increase in the odds of impaired cognition (P < 0.01). Higher NfL and pTau-181 were associated with lower psychomotor and mental efficiency (P < 0.001) but not poorer memory. Amyloid-ß measures were not associated with study measures. A 1% increase in mean HbA1c was associated with a 14.6% higher NfL and 12.8% higher pTau-181 (P < 0.0001). CONCLUSIONS: In this aging T1D cohort, biomarkers of brain injury did not demonstrate an AD-like profile. NfL emerged as a biomarker of interest in T1D because of its association with higher HbA1c, accelerated brain aging on MRI, and cognitive dysfunction. Our study suggests that early neurodegeneration in adults with T1D is likely due to non-AD/nonamyloid mechanisms.

Nocturnal hypoglycemia is associated with next day cognitive performance in adults with type 1 diabetes: Pilot data from the GluCog study.

OBJECTIVE:  Individuals with type 1 diabetes (T1D) have increased risk for cognitive dysfunction and high rates of sleep disturbance. Despite associations between glycemia and cognitive performance using cross-sectional and experimental methods few studies have evaluated this relationship in a naturalistic setting, or the impact of nocturnal versus daytime hypoglycemia. Ecological Momentary Assessment (EMA) may provide insight into the dynamic associations between cognition, affective, and physiological states. The current study couples EMA data with continuous glucose monitoring (CGM) to examine the within-person impact of nocturnal glycemia on next day cognitive performance in adults with T1D. Due to high rates of sleep disturbance and emotional distress in people with T1D, the potential impacts of sleep characteristics and negative affect were also evaluated. METHODS:  This pilot study utilized EMA in 18 adults with T1D to examine the impact of glycemic excursions, measured using CGM, on cognitive performance, measured via mobile cognitive assessment using the TestMyBrain platform. Multilevel modeling was used to test the within-person effects of nocturnal hypoglycemia and hyperglycemia on next day cognition. RESULTS:  Results indicated that increases in nocturnal hypoglycemia were associated with slower next day processing speed. This association was not significantly attenuated by negative affect, sleepiness, or sleep quality. CONCLUSIONS:  These results, while preliminary due to small sample size, showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive fluctuation in real world settings, an approach that may be utilized in other populations. Findings suggest reducing nocturnal hypoglycemia may improve cognition in adults with T1D.

Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.

Background: Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3 months after discharge. Methods: 13 ARF survivors (mean age 51 years and 69% males) completed actigraphy and sleep diaries for 9 days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results: Global circadian function was associated with global cognition function in ARF survivors (r = .70, p = .024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r = .85, p = .002), and weaker circadian strength (estimated by amplitude, r = .66, p = .039; relative strength, r = .70, p = .024; 24-h lag serial autocorrelation, r = .67, p = .035), were associated with global cognition and individual cognitive tests. Conclusions: These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors.

Intraindividual Cognitive Variability and Magnetic Resonance Imaging in Aging American Indians: Data from the Strong Heart Study.

BACKGROUND: American Indians have high prevalence of risk factors for Alzheimer's disease and related dementias (ADRD) compared to the general population, yet dementia onset and frequency in this population are understudied. Intraindividual cognitive variability (IICV), a measure of variability in neuropsychological test performance within a person at a single timepoint, may be a novel, noninvasive biomarker of neurodegeneration and early dementia. OBJECTIVE: To characterize the cross-sectional associations between IICV and hippocampal, total brain volume, and white matter disease measured by magnetic resonance imaging (MRI) among older American Indians. METHODS: IICV measures for memory, executive function, and processing speed, and multidomain cognition were calculated for 746 American Indians (aged 64-95) who underwent MRI. Regression models were used to examine the associations of IICV score with hippocampal volume, total brain volume, and graded white matter disease, adjusting for age, sex, education, body mass index, intracranial volume, diabetes, stroke, hypertension, hypercholesterolemia, alcohol use, and smoking. RESULTS: Higher memory IICV measure was associated with lower hippocampal volume (Beta = -0.076; 95% CI -0.499, -0.023; p = 0.031). After adjustment for Bonferroni or IICV mean scores in the same tests, the associations were no longer significant. No IICV measures were associated with white matter disease or total brain volume. CONCLUSION: These findings suggest that the IICV measures used in this research cannot be robustly associated with cross-sectional neuroimaging features; nonetheless, the results encourage future studies investigating the associations between IICV and other brain regions, as well as its utility in the prediction of neurodegeneration and dementia in American Indians.

Assessing Clinically Significant Cognitive Impairment Using the NIH Toolbox in Individuals with Co-occurring Serious Mental Illness and Alcohol Use Disorder.

OBJECTIVE: Serious mental illnesses (SMI) and alcohol use disorder (AUD) co-occurrence (SMI-AUD) is common, yet little is known about the prevalence and risk factors of cognitive impairment for this population. We used the National Institutes of Health (NIH) Toolbox to identify clinically significant cognitive impairment (CSCI), describe the cognitive profile, and investigate whether psychiatric and AUD severity measures are associated with CSCI in individuals with SMI-AUD. METHODS: CSCI was defined as 2 or more fully corrected fluid subtest T scores below a set threshold based on an individual's crystalized composite score. Psychiatric severity measures included the Structured Clinical Interview for DSM-V (SCID-5) for SMI diagnosis and the Positive and Negative Syndrome Scale. AUD severity measures included the SCID-5 for AUD symptom severity score, years of alcohol use, and urine ethyl glucuronide levels. A multivariable logistic regression was used to investigate the adjusted effects of each variable on the probability of CSCI. RESULTS: Forty-one percent (N = 55/135) of our sample had CSCI compared with the base rate of 15% from the NIH Toolbox normative sample. Subtests measuring executive function most frequently contributed to meeting criteria for CSCI (Flanker and Dimensional Change Card Sort). A history of head injury ( P = 0.033), increased AUD symptom severity score ( P = 0.007) and increased negative symptom severity score ( P = 0.027) were associated with CSCI. CONCLUSIONS: Cognition should be considered in the treatment of people with SMI-AUD, particularly in those with history of brain injury, higher AUD symptom severity, and/or negative symptom severity.

Utility of the NIH Toolbox Cognition Battery in middle to older aged adults with longstanding type 1 diabetes: The DCCT/EDIC study.

Objective: Adults with type 1 diabetes (T1D) face an increased risk for cognitive decline and dementia. Diabetes-related and vascular risk factors have been linked to cognitive decline using detailed neuropsychological testing; however, it is unclear if cognitive screening batteries can detect cognitive changes associated with aging in T1D. Method: 1,049 participants with T1D (median age 59 years; range 43-74) from the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, completed the NIH Toolbox Cognition Battery (NIHTB-C) and Montreal Cognitive Assessment (MoCA). Neuropsychological assessments, depression, glycated hemoglobin levels (HbA1c), severe hypoglycemia, T1D complications, and vascular risk factors were assessed repeatedly over 32 years to determine associations with current NIHTB-C performance. Available cognitive data was clinically adjudicated to determine cognitive impairment status. Results: NIHTB-C scores had moderate associations (r = 0.36-0.53) with concurrently administered neuropsychological tests. In multivariate models, prior severe hypoglycemic episodes, depression symptoms, nephropathy, lower BMI, and higher HbA1c and LDL cholesterol were associated with poorer NIHTB-C Fluid Cognition Composite scores. The NIHTB-C adequately detected adjudicated cognitive impairment (Area Under the Curve = 0.86; optimal cut score ≤90). The MoCA performed similarly (Area Under the Curve = 0.83; optimal cut score ≤25). Conclusions: The NIHTB-C is sensitive to the cognitive effects of diabetes-related and vascular risk factors, correlated with neuropsychological testing, and accurately detects adjudicated cognitive impairment. These data support its use as a screening test in middle to older aged adults with T1D to determine if referral for detailed neuropsychological assessment is needed.