Objective Cognitive Function Research Articles

Chronic kidney disease, physical activity and cognitive function in older adults-results from the National Health and Nutrition Examination Survey (2011-2014).

Cognitive impairment is common among persons with chronic kidney disease (CKD), due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differ by PA. We leveraged 3223 participants (≥60 years of age) enrolled in National Health and Nutrition Examination Survey (NHANES, 2011-2014), with at least one measure of objective cognitive function [immediate recall (CERAD-WL), delayed recall (CERAD-DR), verbal fluency (AF), executive function/processing speed (DSST), global (average of four tests) or self-perceived memory decline (SCD)]. We quantified the association between CKD stage {no CKD: estimated glomerular filtration rate [eGFR]≥60mL/min/1.73 m2 and albuminuria [albumin:creatinine ratio (ACR)] <30mg/g; stages G1-G3: eGFR≥60 mL/min/1.73 m2and ACR ≥30mg/goreGFR 30-59 mL/min/1.73 m2;stages G4 and G5: eGFR<30 mL/min/1.73 m2}andcognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally representative estimates. We tested whether associations differed by PA [Global Physical Activity Questionnaire, high PA≥600 metabolic equivalent of task (MET) · min/week versus low PA<600 MET · min/week] using a Wald test. Among NHANES participants, 34.9% had CKD stages G1-G3, 2.6% had stages G4 and G5 and 50.7% had low PA. CKD stages G4 and G5 were associated with lower global cognitive function {difference = -0.38 standard deviation [SD] [95% confidence interval (CI) -0.62 to -0.15]}. This association differed by PA (Pinteraction=0.01). Specifically, among participants with low PA, those with CKD stages G4 and G5 had lower global cognitive function [difference = -0.57 SD (95% CI -0.82 to -0.31)] compared with those without CKD. Among those with high PA, no difference was found [difference=0.10 SD (95% CI -0.29-0.49)]. Similarly, the CKD stage was only associated with immediate recall, verbal fluency, executive function and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. CKD is associated with lower objective cognitive function among those with low but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines.

The Paradoxical Effect of Living Alone on Cognitive Reserve and Mild Cognitive Impairment among Women Aged 60+ in Mexico City.

An elderly person who lives alone must often be autonomous and self-sufficient in daily living activities. We explored if living alone and marital status were associated with mild cognitive impairment and low cognitive reserve in a sample of Mexican women aged 60+ attending continuing education courses using a cross-sectional design. Objective cognitive functions were assessed using the MMSE and Blessed Dementia Scale. We administered the Cognitive Reserve Questionnaire. Independence skills were assessed with the Katz index and Lawton index. Multivariate logistic regression analysis was used. We recruited 269 participants ( = 69.0 ± 5.8 years). Single, widowed, separated, and divorced women comprised 73% of the participants. A third lived alone and 84% had completed high school. Mild cognitive deficit was observed among 24.5–29.0%; the upper range for cognitive reserve was 61.7%. Living alone versus living with someone was associated with cognitive impairment (OR = 0.51, p = 0.04) and with low to medium cognitive reserve (OR = 0.51, p = 0.02) after adjusting for confounding variables. Living alone was an independent factor associated with a lower probability of displaying mild cognitive impairment and a higher probability of displaying high cognitive reserve. Women living alone in this study had a more robust cognitive framework and had built their own support networks.

The effects of neuroplasticity-based auditory information processing remediation in adults with chronic traumatic brain injury.

Adults with chronic traumatic brain injury (TBI) may experience long-term deficits in multiple cognitive domains. Higher-order functions, such as verbal memory, are impacted by deficits in the ability to acquire verbal information. This study investigated the effects of a neuroplasticity-based computerized cognitive remediation program for auditory information processing in adults with a chronic TBI. Forty-eight adults with TBI were randomly assigned to an intervention or control group. Both groups underwent a neuropsychological assessment at baseline and post-training. The Intervention group received 40 one-hour cognitive training sessions with the Brain Fitness Program. The intervention group improved in performance on measures of the Woodcock-Johnson-III Understanding Directions subtest and Trail Making Test Part-A. They also reported improvement on the cognitive domain of the Cognitive Self-Report Questionnaire. The present study demonstrated that a neuroplasticity-based computerized cognitive remediation program may improve objective and subjective cognitive function in adults with TBI several years post-injury.

Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging

Disrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid β [Aβ]), depression, and cardiovascular disease. To investigate the associations between self-reported sleep duration and brain Aβ burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition. This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, which is being conducted in 67 sites in the United States, Canada, Australia, and Japan. The sample for this analysis consisted of individuals aged 65 to 85 years who underwent an Aβ positron emission tomography (PET) scan, had complete apolipoprotein E (APOE) genotype data, and were identified as clinically normal (per a Clinical Dementia Rating score of 0) and cognitively unimpaired (per a Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Data were analyzed from April 3, 2020, to June 20, 2021. The outcome was self-reported nightly sleep duration (grouped by short sleep duration: ≤6 hours, normal sleep duration: 7-8 hours, and long sleep duration: ≥9 hours) compared with demographic characteristics, Aβ burden (as measured with a fluorine 18-labeled-florbetapir PET scan), objective and subjective cognitive function measures, and lifestyle variables. The 4417 participants in the study included 2618 women (59%) and had a mean (SD) age of 71.3 (4.7) years. Self-reported shorter sleep duration was linearly associated with higher Aβ burden (β [SE] = -0.01 [0.00]; P = .005), and short sleep duration was associated with reduced cognition that was mostly in memory domains. No difference in Aβ was found between long and normal sleep duration groups (β [SE] = 0.00 [0.01]; P = .99). However, compared with normal sleep duration, both short and long sleep durations were associated with higher body mass index (short vs normal sleep duration: β [SE] = 0.48 [0.17], P = .01; long vs normal sleep duration: β [SE] = 0.97 [0.31], P = .002), depressive symptoms (short vs normal sleep duration: β [SE] = 0.31 [0.05], P < .001; long vs normal sleep duration: β [SE] = 0.39 [0.09], P < .001), and daytime napping (short vs normal sleep duration: β [SE] = 2.66 [0.77], P = .001; long vs normal sleep duration: β [SE] = 3.62 [1.38], P = .01). Long sleep duration was associated with worse performance across multiple cognitive domains. In this cross-sectional study, both short and long sleep durations were associated with worse outcomes for older adults, such as greater Aβ burden, greater depressive symptoms, higher body mass index, and cognitive decline, emphasizing the importance of maintaining adequate sleep.

Comorbidity, cognitive dysfunction, physical functioning, and quality of life in older breast cancer survivors

PurposeOlder breast cancer survivors (BCS) may be at greater risk for cognitive dysfunction and other comorbidities; both of which may be associated with physical and emotional well-being. This study will seek to understand these relationships by examining the association between objective and subjective cognitive dysfunction and physical functioning and quality of life (QoL) and moderated by comorbidities in older BCS.MethodsA secondary data analysis was conducted on data from 335 BCS (stages I–IIIA) who were ≥ 60 years of age, received chemotherapy, and were 3–8 years post-diagnosis. BCS completed a one-time questionnaire and neuropsychological tests of learning, delayed recall, attention, working memory, and verbal fluency. Descriptive statistics and separate linear regression analyses testing the relationship of each cognitive assessment on physical functioning and QoL controlling for comorbidities were conducted.ResultsBCS were on average 69.79 (SD = 3.34) years old and 5.95 (SD = 1.48) years post-diagnosis. Most were stage II (67.7%) at diagnosis, White (93.4%), had at least some college education (51.6%), and reported on average 3 (SD = 1.81) comorbidities. All 6 physical functioning models were significant (p < .001), with more comorbidities and worse subjective attention identified as significantly related to decreased physical functioning. One model found worse subjective attention was related to poorer QoL (p < .001). Objective cognitive function measures were not significantly related to physical functioning or QoL.ConclusionsA greater number of comorbidities and poorer subjective attention were related to poorer outcomes and should be integrated into research seeking to determine predictors of physical functioning and QoL in breast cancer survivors.

Life satisfaction and emotional distress in people living with type 2 diabetes mellitus: The mediating effect of cognitive function

To explore the relationships among emotional distress, cognitive function, and life satisfaction in people living with type 2 diabetes mellitus (T2DM), and to verify the mediating role of cognitive function. People with T2DM face cognitive decline caused by age and disease complications. Emotional distress will reduce their life satisfaction, and cognitive function will also affect the life satisfaction, but whether cognitive function mediates the effect of emotional distress on life satisfaction has not been verified. A cross-sectional study. A total of 200 people living with T2DM in the community by convenience sampling were enrolled from November - December 2018. Data collection involved a demographic and disease characteristics questionnaire, Problem Areas in Diabetes Scale, Subjective and Objective Cognitive Function Evaluation, and Life Satisfaction Questionnaire. Data analysis included descriptive statistics and structural equation modeling. This report followed the STROBE guideline. The emotional distress and subjective memory complaints of cognitive function had a significant positive correlation, while both emotional distress and cognitive function showed significant negative correlations with life satisfaction. In addition, cognitive function completely mediated the relationship between emotional distress and life satisfaction. The cognitive function played a mediating role in life satisfaction and explain how emotional distress affects life satisfaction of people with T2DM. Therefore, it is suggested that diabetes nurses should early identify the decline of cognitive function, and to intervene at early stage. This study provides opinions on the mediating factors of cognitive function. Coping strategies and supporting resources to help the T2DM people to improve their life satisfaction is suggested.

Effect of Baduanjin exercise intervention on cognitive function and quality of life in women with breast cancer receiving chemotherapy: study protocol of a randomized controlled trial

BackgroundMore than 50% cognitive impairment was reported by cancer patients before and after medical treatment. However, there are no effective interventions to manage the cognitive problem in women with breast cancer. This pilot study was designed to evaluate the protective effect of Baduanjin exercise on cognitive function and cancer-related symptoms in women with early-stage breast cancer undergoing chemotherapy.MethodA single-blinded, randomized control trial was designed. The trial will recruit 70 patients with early-stage breast cancer scheduled to receive chemotherapy from Shanghai in China. All participants will be randomly assigned to (1:1) the supervised Baduanjin group (5 times/week, 30 min each time) or the wait-list control group for 3 months. The effect of Baduanjin exercise intervention will be evaluated by outcome measures including subjective and objective cognitive function, symptoms (fatigue, depression, and anxiety), and health-related quality of life at pre-intervention (T0), 8 weeks (T1), and 12 weeks (T2). The PCI score in the FACT-Cog as the primary cognitive outcome will be reported descriptively, while effect sizes and 95% confidence intervals (CIs) will be calculated. The collected data will be analyzed by using an intention-to-treat principle and linear mixed-effects modeling.DiscussionThis is the first randomized clinical trial to investigate whether Baduanjin exercise will have a positive role in improving cognitive function in women with breast cancer receiving chemotherapy. If possible, Baduanjin exercise will be a potential non-pharmacological intervention to manage cognitive dysfunction and promote survivorship care among breast cancer survivors.Trial registrationChinese Clinical Trial Registry (ChiCTR) ChiCTR2000033152. Registered on 22 May 2020

Within-day rhythms of pain and cognitive function in people with and without fibromyalgia: synchronous or syncopated?

Cognitive dysfunction is a common fibromyalgia (FM) symptom and can impact on the daily lives of those affected. We investigated whether within-day pain intensity ratings were associated with contemporaneous objective and subjective measures of cognitive function and whether within-day increases in pain intensity preceded increases in cognitive dysfunction or vice versa. Inclusion of a non-FM group allowed us to examine whether effects were specific to FM. Fifty people with FM and 50 non-FM controls provided 7 days of data. Cognitive tests (processing speed and working memory) and ecological momentary assessments (pain intensity and self-reported cognitive functioning) were conducted ×5/day. Three-level multilevel models examined contemporaneous and within-day 1-lag pain intensity-cognitive functioning associations. Interaction terms assessed possible moderating effects of FM status. Momentary increase in pain was associated with increased self-reported cognitive dysfunction, more strongly so for those with FM (B = 0.27, 95% confidence interval 0.22-0.32; non-FM B = 0.17, 95% confidence interval 0.10-0.23). For the FM group, higher pain was associated with longer processing speed; for the non-FM group, higher pain was associated with shorter processing speed. Pain increase did not precede change in subjective or objective cognitive function in the FM group, but reduction in working memory preceded increase in pain intensity. This finding warrants further research attention and, if replicated, could hold prognostic and/or therapeutic potential.

Cognitive function in men with non-motor features of Parkinson’s disease

ObjectiveSubtle cognitive deficits can occur during the prodromal phase of Parkinson’s disease (PD), commonly in conjunction with hyposmia. However, little is known about the association between cognitive function and other...

Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer.

Simple SummaryAlthough cognitive impairments have been complained about in patients with breast cancer who underwent chemotherapy, recent research has described possible neurocognitive decline prior to the start of chemotherapy and suggested that inflammatory cytokines may also have been involved. However, inconsistencies have been found in correlations of cognitive impairments with cancer, chemotherapy, and peridiagnostic cytokine levels. This cross-sectional study aimed to examine associations of cognitive functions and levels of cytokines in patients with newly- diagnosed breast cancer before chemotherapy, those that were 3 to 9 months after completing chemotherapy, and non-cancer controls, adjusting for baseline intelligence quotient, mood, and fatigue. We found that the performance in semantic association of verbal fluency in patients post chemotherapy might be affected by the status of cancer, IL-13, and anxiety. Our results indicated that verbal fluency and anxiety may be important when considering relevant psychosocial managements or prophylactic interventions for cognitive preservation associated with regulations in cytokines.Background: We aimed to investigate the associations of breast cancer (BC) and cancer-related chemotherapies with cytokine levels, and cognitive function. Methods: We evaluated subjective and objective cognitive function in BC patients before chemotherapy and 3~9 months after the completion of chemotherapy. Healthy volunteers without cancer were also compared as control group. Interleukins (IL) 2, 4, 5, 6, 10, 12p70, 13, 17A, 1β, IFNγ, and TNFα were measured. Associations of cancer status, chemotherapy and cytokine levels with subjective and objective cognitive impairments were analyzed using a regression model, adjusting for covariates, including IQ and psychological distress. Results: After adjustment, poorer performance in semantic verbal fluency was found in the post-chemotherapy subgroup compared to controls (p = 0.011, η2 = 0.070); whereas pre-chemotherapy patients scored higher in subjective cognitive perception. Higher IL-13 was associated with lower semantic verbal fluency in the post-chemotherapy subgroup. Higher IL-10 was associated with better perceived cognitive abilities in the pre-chemotherapy and control groups; while IL-5 and IL-13 were associated with lower perceived cognitive abilities in pre-chemotherapy and control groups. Our findings from mediation analysis further suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Conclusions: Our findings suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Different cytokines and their interactions may have different roles of neuroinflammation or neuroprotection that need further research.

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: A randomized controlled trial (PAM study).

12015 Background: Chemotherapy is associated with cognitive problems. Physical exercise is a promising intervention. We investigated whether exercise improves cognition in chemotherapy-exposed breast cancer (BC) patients 2-4 years after diagnosis. Methods: In the PAM study, we randomized chemotherapy-exposed BC patients with self-reported and test-confirmed cognitive problems to an exercise or control group. The 6-month exercise intervention consisted of 2 hours of supervised aerobic and resistance training and two hours of Nordic/power walking. Memory function measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) was our primary outcome. Further measurements included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognitive complaints (MDASI-MM, EORTC QLQ C-30 cognitive functioning), physical fitness (VO2peak), fatigue (MFI, EORTC fatigue), quality of life (QoL; EORTC), anxiety (HADS) and depression (HADS, PHQ9). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement of ≥5 words. Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. An hypothesis driven but not pre-specified analysis in patients with high baseline EORTC fatigue levels (≥39) was performed. Results: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise program and physical fitness significantly improved compared to the control patients ( VO2peak1.4 ml/min/kg, 95% CI 0.6; 2.2). No difference in favor of the intervention group was seen on the primary cognitive outcome or other cognitive tests. However, significant beneficial intervention effects were found for self-reported cognition (MDASI-MM Severity (-0.7, -1.2;-0.1)), fatigue (general fatigue (-2.2, -3.3; -1.1), physical fatigue (-3.3, -4.4; -2.2), mental fatigue (-1.0, -2.0; 0.0), reduced motivation (-1.1, -2.0; -0.2) and reduced activity (-2.1, -3.2; -1.1)), QoL (summary score (4.0, 1.2; 6.7), global health status (5.8, 1.1; 10.6), role functioning (7.2, 1.3; 13.1) and social functioning (5.9, 0.2; 11.6)) and depression (PHQ9 (-1.16, -2.19; -0.13)). In high-fatigued patients, exercise did show significant positive effects on objective cognitive function (ACS Reaction Time (-26.8, -52.9; -0.6) and ACS Wordlist Learning (4.4, 0.5; 8.3)). Conclusions: A 6-month exercise intervention did not improve objectively measured cognitive function in chemotherapy-exposed BC patients with cognitive problems. However, self-reported cognitive function, physical fitness, fatigue, QoL and depression did improve. Unplanned analysis indicated a small positive effect of exercise on cognitive functioning in high-fatigued patients. Clinical trial information: NTR6104.

Psychiatric and cognitive characteristics of older adults admitted to a Video-EEG monitoring (VEM) unit

ObjectiveTo compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit. MethodThis was a retrospective case–control study involving patients admitted for VEM over a two-year period (from April 2018 to April 2020) at two comprehensive epilepsy units. Patients were categorized into an older (≥60 years) and a younger (<60 years) group. Younger patients were individually matched to older adults to form a matched younger group. Diagnosis was determined by a consensus opinion of epileptologists, neurologists, and neuropsychiatrists. The main diagnostic categories were epilepsy, psychogenic nonepileptic seizures (PNES), and ‘other’ diagnosis (non-diagnostic and other nonepileptic diagnoses). Clinical psychiatric diagnoses were obtained from neuropsychiatric reports. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Subjective cognitive function was assessed using the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) cognitive subscales. ResultsFive-hundred and thirty three patients (71 older, 462 younger) aged 16–91 years were admitted to the VEM unit during the study period. There was a diagnosis of focal epilepsy in 55% of the older group and 48% of the younger group, generalized epilepsy in 3% of the older group and 10% of the younger group, and ‘other’ in 32% of the older group and 19% of the younger group. Ten percent (2 males and 5 females) of the older group were diagnosed with PNES compared to 22% of the younger group (p = 0.016). A depressive disorder was diagnosed in 34% of the older group and 24% of the younger group (p = 0.20). An anxiety disorder was diagnosed in 15% of the older group and 25% of the younger group (p = 0.15). Mild neurocognitive disorder was more common in the older group (34%) compared to the matched younger group (34% vs 3%, p < 0.001). The older group had lower mean NUCOG scores compared to the matched younger group (79.49 vs 87.73, p = <0.001). There was no evidence for a relationship between mean NUCOG score and overall subjective cognitive difficulties for the older group (r = 0.03, p = 0.83). Among older adults, those diagnosed with PNES had more experiences of childhood trauma. Measures of dissociation, depression, or general anxiety did not differ between PNES and non-PNES diagnoses in the older group. ConclusionPsychiatric comorbidities are common among older adults admitted for VEM. The psychological impact of epilepsy and risk factors for PNES seen in younger patients are also applicable in the older group. The older group demonstrated more cognitive impairments than the younger group, although these were usually unrecognized by individuals. Older adults admitted to VEM will benefit from psychiatric and neuropsychological input to ensure a comprehensive care approach to evaluation and management.

Effects of Combined Physical Activity and Cognitive Training on Cognitive Function in Older Adults with Subjective Cognitive Decline: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Subjective cognitive decline (SCD) is recognized as the earliest prodromal stage of Alzheimer’s disease (AD). Emerging studies explored the effects of combined physical activity and cognitive training interventions on cognitive ability, psychological well-being, and emotion of older adults with SCD, but the results are now still controversial. Objective. This study systematically evaluated the enhancement effects of the combined physical-cognitive interventions on memory self-efficacy, objective cognitive function, psychological well-being, and emotion of older adults with SCD. Methods. Data sources PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang degree and conference papers database, Chinese Science and Technology Periodical (VIP) databases from their inception to 28 February 2020, the Cochrane Central Register of Controlled Trials (Cochrane Library, 2020, Issue 3), and the reference lists of all retrieved articles were searched. Data analysis and bias risk evaluation were conducted in 2020. Two reviewers (SG and YY) independently evaluated the risk of bias of the included studies using the RoB 2 tool. Results. Eleven RCTs involving 1713 participants with SCD (age 68.0 ± 6.1) were included for review and meta-analysis. The interventions in the included studies were physical activity combined with cognitive training. Multiple-modality exercise with mind-motor training, supervised strategy-based memory training sequentially after stationary cycling, Dejian Mind-Body intervention, and physical activity and cognitive stimulation were also practiced. Conclusions. Compared to the active or nonactive control groups, the combined interventions are effective in improving objective cognitive function in SCD which may show the potential value of combined physical-cognitive interventions in improving objective cognitive ability and preventing the conversion of SCD to MCI or AD and no adverse effects. However, owing to the limitations of the included studies, these findings should be interpreted cautiously.

Sleep symptomatology is associated with greater subjective cognitive concerns: findings from the community-based Healthy Brain Project.

To examine if sleep symptomatology was associated with subjective cognitive concerns or objective cognitive performance in a dementia-free community-based sample. A total of 1,421 middle-aged participants (mean ± standard deviation = 57 ± 7; 77% female) from the Healthy Brain Project completed the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale to measure sleep quality, insomnia symptom severity, and daytime sleepiness, respectively. Participants were classified as having no sleep symptomatology (normal scores on each sleep measure), moderate sleep symptomatology (abnormal scores on one sleep measure), or high sleep symptomatology (abnormal scores on at least two sleep measures), using established cutoff values. Analysis of covariance was used to compare objective cognitive function (Cogstate Brief Battery) and subjective cognitive concerns (Modified Cognitive Function Instrument) across groups. Following adjustments for age, sex, education, mood, and vascular risk factors, persons classified as having high sleep symptomatology, versus none, displayed more subjective cognitive concerns (d = 0.24) but no differences in objective cognitive performance (d = 0.00-0.18). Subjective cognitive concerns modified the association between sleep symptomatology and psychomotor function. The strength of the relationship between high sleep symptomatology (versus none) and psychomotor function was significantly greater in persons with high as compared with low cognitive concerns (β ± SE = -0.37 ± 0.16; p = 0.02). More severe sleep symptomatology was associated with greater subjective cognitive concerns. Persons reporting high levels of sleep symptomatology may be more likely to display poorer objective cognitive function in the presence of subjective cognitive concerns.

NIA-AA Alzheimer's Disease Framework: Clinical Characterization of Stages.

BackgroundTo operationalize the National Institute on Aging – Alzheimer's Association (NIA‐AA) Research Framework for Alzheimer's Disease 6‐stage continuum of clinical progression for persons with abnormal amyloid.MethodsThe Mayo Clinic Study of Aging is a population‐based longitudinal study of aging and cognitive impairment in Olmsted County, Minnesota. We evaluated persons without dementia having 3 consecutive clinical visits. Measures for cross‐sectional categories included objective cognitive impairment (OBJ) and function (FXN). Measures for change included subjective cognitive impairment (SCD), objective cognitive change (ΔOBJ), and new onset of neurobehavioral symptoms (ΔNBS). We calculated frequencies of the stages using different cutoff points and assessed stability of the stages over 15 months.ResultsAmong 243 abnormal amyloid participants, the frequencies of the stages varied with age: 66 to 90% were classified as stage 1 at age 50 but at age 80, 24 to 36% were stage 1, 32 to 47% were stage 2, 18 to 27% were stage 3, 1 to 3% were stage 4 to 6, and 3 to 9% were indeterminate. Most stage 2 participants were classified as stage 2 because of abnormal ΔOBJ only (44–59%), whereas 11 to 21% had SCD only, and 9 to 13% had ΔNBS only. Short‐term stability varied by stage and OBJ cutoff points but the most notable changes were seen in stage 2 with 38 to 63% remaining stable, 4 to 13% worsening, and 24 to 41% improving (moving to stage 1).InterpretationThe frequency of the stages varied by age and the precise membership fluctuated by the parameters used to define the stages. The staging framework may require revisions before it can be adopted for clinical trials. ANN NEUROL 2021;89:1145–1156

Structural Neuroimaging Findings Related to Adult Non-CNS Cancer and Treatment: Review, Integration, and Implications for Treatment of Cognitive Dysfunction.

Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.

Subjective cognitive and neurocognitive functions over the course of CBT

The aim of the study was to investigate changes in both subjectively and objectively measured cognitive functions as well as their discrepancy in outpatients with major depression disorder in the course of cognitive-behavioural therapy (CBT). A neuropsychological test battery with cognitive tests measuring the domains of attention, memory, and executive functions as well as a questionnaire for the self-assessment of cognitive functions (FLei) in these domains were administered to depressed outpatients (n = 46) at the beginning of CBT, post-treatment after on average 40 sessions, as well as six months after the end of treatment. We found that subjectively as well as objectively measured cognitive functions did not change. The discrepancy between subjective and objective cognitive functions found at the beginning of therapy was no longer significant at post-treatment and six months later. The results indicate, that self-perceived and neuropsychologically measured cognitive impairments show stability despite improved depression. Specific interventions such as cognitive remediation therapy should be additionally applied to depressed patients who suffer from cognitive deficits.

The Interaction of Inflammatory Markers and Alcohol-Use on Cognitive Function in Korean Male Firefighters.

ObjectiveCognitive functions have been shown to become impaired due to alcoholism. Recently, neuroinflammation gained attention for playing a role in the neurotoxic effect of alcohol. However, there is limited data on the relationship between alcohol and cognitive function, based on the mechanism of inflammation. This study examined whether the interaction between alcohol use and pro-inflammatory biomarkers is related to cognitive function in Korean male firefighters. MethodsA total of 474 firefighters were assessed for alcohol-related problems using CAGE, cognitive functions, and pro-inflammatory biomarkers (CRP, IL-6, TNF-α). Sequential multiple regression analyses were conducted to determine if inflammatory markers moderate the relationship between alcohol use and cognitive function. ResultsOnly a decreased attentional function was associated with the interaction of alcohol use and inflammatory markers, after controlling for age, sex, body mass index, lipid profiles, smoking, depression, fatigue, self-reported hypertension, diabetes, and musculoskeletal problems. ConclusionThis study revealed that the interaction between alcohol use and inflammation is related to attentional function in Korean male firefighters. Additionally, this cross-sectional study suggests that diminishing attention, related to alcohol use, may be based on the mechanism of inflammation.

Discordance Between Subjective and Objective Cognitive Function in Older Korean Americans.

Objectives: To examine predictors of membership in discordant groups identified by subjective and objective measures of cognitive function. Methods: Participants in the Study of Older Korean Americans (N = 2046) were classified according to their subjective cognitive ratings (excellent/very good/good vs. fair/poor) and Mini-Mental State Examination scores (normal cognition vs. cognitive impairment), yielding two discordant groups: (1) positive ratings but cognitive impairment and (2) negative ratings but normal cognition. Logistic regression models examined how the discordant group membership was associated with personal resources. Results: Among those with positive cognitive ratings, the odds of belonging to the discordant group were associated with low personal resources (advanced age and lower levels of education, acculturation, and knowledge about Alzheimer's disease). However, an opposite pattern was observed among those with negative ratings. Discussion: The pattern of discordance suggests ways to promote early detection of cognitive impairment and close the gap in cognitive health care.

The effect of improved dietary control on cognitive and psychiatric functioning in adults with phenylketonuria: the ReDAPT study

BackgroundPhenylketonuria (PKU) is an autosomal recessive inherited disorder characterised by a deficiency in phenylalanine hydroxylase. Untreated, PKU is associated with a wide range of cognitive and psychiatric sequelae. Contemporary management guidelines recommend lifetime dietary control of phenylalanine (Phe) levels, however many individuals who discontinue dietary control subsequently suffer symptoms of anxiety, depression and disturbances to cognition. We undertook a prospective cohort study of patients with early-treated phenylketonuria who had ceased dietary control to test the hypothesis that resumption of dietary control of PKU is associated with improvements in measures of psychiatric morbidity and cognitive functioning.MethodsWe re-initiated dietary control for early-treated patients with PKU and monitored cognitive and psychiatric outcomes over a twelve-month period. Assessments included objective cognitive function (measured by cognitive proficiency index (CPI)), anxiety and depression scales. General linear mixed model (GLMM) analyses were performed to assess change in psychometric variables from baseline over twelve months after resumption of dietary control.ResultsA total of nine patients were recruited. Mean age was 33 years (SD = 8.75), five were female. Mean time off dietary control was 19.1 years (SD = 11.3), and mean baseline phenylalanine (Phe) levels were 1108 µmol/L (SD = 293). GLMM analysis demonstrated a positive relationship between CPI and time on diet (b = 0.56 [95% CI = 0.17, 0.95]). Age, time off diet, Phe levels and depression scores were not associated with cognitive function. There was a negative relationship between time on diet and anxiety (b = − 0.88 95% CI = [− 1.26, − 0.50]) and depression ratings (b = − 0.61, 95% CI = [− 0.95, − 0.26]).ConclusionsThis study demonstrated improvements in cognitive function, anxiety, and depression ratings associated with resumption of dietary control of PKU. Raw Phe levels were not strongly associated with psychiatric or cognitive scores in this cohort. These findings support the importance of lifelong treatment for PKU in improving the cognitive and psychiatric sequelae of the disease.