Substantial Cognitive Impairment Research Articles

Severe Cognitive Impairment in Trauma-Affected Refugees—Exploring the Impact of Traumatic Brain Injury

Background/Objectives: This study explores the relationship between cognitive performance measured by the Symbol Digit Modality Test (SDMT) and the severity of self-reported head injury, traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, pain, and psychosocial dysfunction in a population of trauma-affected refugees. Refugees, especially those who have been subjected to torture, often face various difficulties, such as PTSD, depression and somatic disturbances (e.g., pain), which can significantly impact their day-to-day functioning. Methods: Participants included 141 adult refugees (38% women) with a mean age of 45.4 years (SD = 9.4) and 9.7 years (SD = 4.9) of education who were referred for treatment of post-traumatic distress to DIGNITY, Danish Institute Against Torture. Participants completed standardized self-report measures of PTSD, anxiety, depression, pain, and health-related disability and measures of trauma history, physical injuries including head injury and loss of consciousness, and the SDMT, a quick standardized performance-based measure of cognitive impairment. Results: Eighty-eight percent of participants evidenced signs of substantial cognitive impairment as indexed by lower SDMT scores. Those with a self-reported history of TBI, marked by loss of consciousness, exhibited lower SDMT scores and higher health-related disabilities. Severity of PTSD, depression, anxiety, and pain were highly correlated with lower SDMT scores. TBI history was not significantly associated with the severity of PTSD, depression, anxiety, or pain, suggesting a complex interplay among these factors. Conclusions: Cognitive impairments are prevalent in trauma-affected refugees, interacting with symptoms of post-traumatic stress and pain, likely explaining the high disability levels in this population. Further research should employ a broader range of cognitive measures and detailed investigations of head injury/TBI experiences to investigate their impact on overall functioning, treatment response, and longer-term outcomes. This study adds to a small but growing body of studies documenting cognitive impairments in trauma-affected refugees, highlighting the importance of addressing cognitive impairments in treatment for trauma-affected refugees, particularly those with histories of torture and TBI. Clinicians working with trauma-affected refugees should consider the assessment of cognitive difficulties as part of comprehensive care planning.

Recruitment and baseline data of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study: A randomized trial of a hearing loss intervention for reducing cognitive decline.

Hearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best-practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results. Multiple strategies were used to recruit community-dwelling 70-84-year-old participants with adult-onset hearing loss who were free of substantial cognitive impairment from the parent ARIC study and de novo from the surrounding communities into the trial. Participants completed telephone screening, an in-person hearing, vision, and cognitive screening, and a comprehensive hearing assessment to determine eligibility. Over a 24-month period, 3004 telephone screenings resulted in 2344 in-person hearing, vision, and cognition screenings and 1294 comprehensive hearing screenings. Among 1102 eligible, 977 were randomized into the trial (median age = 76.4 years; 53.5% female; 87.8% White; 53.3% held a Bachelor's degree or higher). Participants recruited through the ARIC study were recruited much earlier and were less likely to report hearing loss interfered with their quality of life relative to participants recruited de novo from the community. Minor differences in baseline hearing or health characteristics were found by recruitment route (i.e., ARIC study or de novo) and by study site. The ACHIEVE study successfully completed enrollment over 2 years that met originally projected rates of recruitment. Substantial operational and scientific efficiencies during study startup were achieved through embedding this trial within the infrastructure of a longstanding and well-established observational study. The ACHIEVE study tests the effect of hearing intervention on cognitive decline.The study is partially nested within an existing cohort study.Over 2 years, 977 participants recruited and enrolled.Eligibility assessed by telephone and in-person for hearing, vision, and cognitive screening.The ACHIEVE study findings will have significant public health implications.

Association between physical function and neuroimaging measures in a 2‐year multidomain lifestyle randomized controlled trial

AbstractBackgroundThis exploratory study investigated associations between physical function and neuroimaging biomarkers: brain magnetic resonance imaging (MRI) and Pittsburgh compound B‐positron emission tomography (PiB‐PET) measures during the 2‐year Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER).MethodFINGER targeted 60–77‐year‐old general population at‐risk and without dementia or substantial cognitive impairment. Measures of physical function (activities of daily living (ADL), hand grip strength, physical performance, Fried’s frailty phenotype index and self‐rated health) from baseline and 2‐year visits were used. Baseline neuroimaging measures, MRI (hippocampus, total gray matter volumes, Alzheimer’s disease (AD) signature cortical thickness) were available for 115‐132 participants and PiB‐PET (composite score) for 44‐48 participants. Linear and logistic regressions were used to test the cross‐sectional associations and the impact of baseline imaging measures on changes in physical function. Models were adjusted for site, sex and education.ResultCross‐sectionally, higher ADL were associated with higher hippocampus volume (β = 0.18 p = 0.048), total gray matter volume (β = 0.15 p = 0.005) and AD signature cortical thickness (β = 0.25 p = 0.006) while stronger hand grip and was associated with higher total gray matter volume (β = 0.20 p = 0.041) significantly. Baseline imaging measures were associated with changes in physical function: higher baseline hippocampus volume was associated with maintenance/improvement in the ADL (OR = 0.56 p = 0.039) while lower hippocampus at baseline predicted poorer physical performance over time (OR = 1.66 p = 0.036).ConclusionHigher brain integrity is associated with better physical function while lower baseline brain integrity predicts poorer physical function over time.

Effects of hearing intervention on cognitive decline: Results of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized trial

AbstractBackgroundHearing loss is associated with greater cognitive decline and incident dementia. Whether hearing intervention could reduce cognitive decline in older adults with hearing loss is unknown.MethodThe ACHIEVE study is a randomized trial (NCT03243422) of 70‐84 year‐old adults with untreated hearing loss and free from substantial cognitive impairment that took place at four U.S. sites. Participants were recruited from two study populations: 1) a group of adults participating in a longstanding observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and 2) a group of healthy de novo community volunteers. Participants were randomised (1:1) to hearing intervention (HI; audiological counseling and provision of hearing aids) or a successful aging health education control intervention (SA; sessions with a health educator on chronic disease prevention). The primary intention‐to‐treat endpoint was 3‐year change in a global cognition standardized factor score from a comprehensive neurocognitive battery.Result977 participants (238 ARIC, 739 de novo) underwent randomisation; 490 were assigned to HI and 487 to SA control. Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than the de novo group. In the primary analysis combining the ARIC and de novo groups, 3‐year cognitive change (in S.D. units) was not significantly different between HI and SA control (HI: ‐0·200 [95% CI: ‐0·256,‐0·144]; SA: ‐0·202 [‐0·258,‐0·145]; Difference 0·002 [‐0·077,0·081],p = 0·96). However, prespecified analyses demonstrated significant differences in the effect of HI on cognitive change between the ARIC and de novo group (p interaction = 0·010). In the ARIC group, HI was associated with a 48% reduction in 3‐year cognitive change compared to SA control (HI: ‐0·211 [‐0·349,‐0·073]; SA: ‐0·402 [‐0·536, ‐0·267]; Difference 0·191 [0·022,0·360,p = 0·027]). In the de novo group, cognitive change was not significantly different between HI and SA control (HI: ‐0·213 [‐0·277,‐0·148]; SA: ‐0·151 [‐0·215,‐0·087]; Difference ‐0·061 [‐0·151,0·028,p = 0·18]). The rate of cognitive change among control participants was observed to be 2.7‐fold faster in the ARIC versus de novo group.ConclusionHearing intervention may have a significant effect on reducing cognitive change over 3 years in populations of older adults at increased risk for cognitive decline.

Digitally supported lifestyle program to promote brain health among older adults (LETHE pilot trial) – Study design and progress

AbstractBackgroundDementia prevention is a global public health priority. The FINGER multimodal lifestyle intervention is the only intervention model so far that has demonstrated significant cognitive and other health benefits in at‐risk older adults. LETHE proposes a new multimodal precision prevention approach where FINGER intervention is complemented with digital tools to optimize intervention delivery, personalize recommendations based on individual risk profile, and support risk factor self‐management. The multinational 2‐year randomized controlled LETHE pilot trial aims to test the feasibility of a digitally supported, adapted FINGER intervention among older adults at risk of cognitive decline and dementia.MethodA total of 160 individuals aged 60‐77 years and with risk factors for dementia but no substantial cognitive impairment are recruited at four sites (Austria, Finland, Italy, Sweden; N = 40 per country). Digital readiness and experience with smart devices are required. Participants are randomized 1:1 to 1) structured multimodal lifestyle intervention (dietary guidance, exercise, cognitive training, vascular/metabolic risk management, social stimulation, sleep/stress management) where in‐person individual and group‐based activities are supported with the LETHE smartphone app developed in the project; or 2) self‐guided lifestyle intervention (regular health advice and access to a simplified app with no personalized/interactive content). Both groups wear a smartwatch to gather passive data (e.g., activity, sleep). Primary outcomes are retention rate, adherence to intervention and engagement with the app, and change in dementia risk based on validated risk scores (CAIDE, LIBRA). Secondary outcomes are lifestyle changes and changes in cognition, stress‐related symptoms, sleep, health‐related quality of life, and health literacy. Participant experiences will also be explored. The LETHE Advisory Board (members of the public) provided feedback on the trial protocol.ResultTrial is registered at ClinicalTrials.gov (NCT05565170), and ethical approval has been obtained in each country. Recruitment started in September 2022 and will be completed in Spring 2023. Updates and results on study progress will be presented.ConclusionLETHE pilot trial will inform about the feasibility of technological solutions and a digitally assisted lifestyle program to support brain health among older adults. If proved to induce sustained behavioural changes, digital tools could offer potential for large‐scale, cost‐effective dementia prevention programs.

Association between physical function and neuroimaging measures in a 2‐year multidomain lifestyle randomized controlled trial

AbstractBackgroundThis exploratory study investigated associations between physical function and neuroimaging biomarkers: brain magnetic resonance imaging (MRI) and Pittsburgh compound B‐positron emission tomography (PiB‐PET) measures during the 2‐year Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER).MethodFINGER targeted 60–77‐year‐old general population at‐risk and without dementia or substantial cognitive impairment. Measures of physical function (activities of daily living (ADL), hand grip strength, physical performance, Fried’s frailty phenotype index and self‐rated health) from baseline and 2‐year visits were used. Baseline neuroimaging measures, MRI (hippocampus, total gray matter volumes, Alzheimer’s disease (AD) signature cortical thickness) were available for 115‐132 participants and PiB‐PET (composite score) for 44‐48 participants. Linear and logistic regressions were used to test the cross‐sectional associations and the impact of baseline imaging measures on changes in physical function. Models were adjusted for site, sex and education.ResultCross‐sectionally, higher ADL were associated with higher hippocampus volume (ß = 0.18 p = 0.048), total gray matter volume (ß = 0.15 p = 0.005) and AD signature cortical thickness (ß = 0.25 p = 0.006) while stronger hand grip and was associated with higher total gray matter volume (ß = 0.20 p = 0.041) significantly. Baseline imaging measures were associated with changes in physical function: higher baseline hippocampus volume was associated with maintenance/improvement in the ADL (OR = 0.56 p = 0.039) while lower hippocampus at baseline predicted poorer physical performance over time (OR = 1.66 p = 0.036).ConclusionHigher brain integrity is associated with better physical function while lower baseline brain integrity predicts poorer physical function over time.

Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial

Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0·200 [95% CI -0·256 to -0·144] in the hearing intervention group and -0·202 [-0·258 to -0·145] in the control group; difference 0·002 [-0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. US National Institutes of Health.

Neuropathologic correlates of cerebral microbleeds in community-based older adults

Cerebral microbleeds (CMBs) appearing as hypointense foci on T2*-weighted magnetic resonance images are small hemorrhages that have been linked to cognitive decline and increased mortality. However, the neuropathologic correlates of CMBs in community-based older adults are poorly understood. The present study investigated the association of age-related neuropathologies with CMBs in community-based older adults. Cerebral hemispheres from 289 participants of the Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and Rush Alzheimer’s Disease Clinical Core underwent ex vivo MRI and detailed neuropathologic examination. Following Bonferroni correction, CMBs in the cerebrum overall and in the frontal lobe were associated with cerebral amyloid angiopathy, CMBs in the frontal lobe were also associated with arteriolosclerosis, and CMBs in the basal ganglia showed a borderline significant association with microinfarcts. These findings suggest that CMBs can aid in the prediction of small vessel disease in community-based older adults. Finally, CMBs were not associated with dementia, suggesting that CMBs in community-based older adults may not be linked to substantial cognitive impairment.

Characteristics of traumatic brain injury models: from macroscopic blood flow changes to microscopic mitochondrial changes.

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model. A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of > 2 mm is used to induce severe brain injury. However, the different effects and underlying mechanisms of these two model types have not been proven. This study investigated the changes in cerebral blood flow, differences in the degree of cortical damage, and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3, 4, and 5 m/s. We also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute (7 days) and chronic phases (30 days). The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased, and swelling and bulging of brain tissue, increased vascular permeability, and large-scale exudation occurred. In the 2 mm group, the main pathological changes were decreased cerebral blood flow, brain tissue loss, and cerebral vasospasm occlusion in the injured area. Substantial motor and cognitive impairments were found on day 7 after injury in the 2 mm group; at 30 days after injury, the motor function of the 2 mm group mice recovered significantly while cognitive impairment persisted. Transcriptome sequencing showed that compared with the 1 mm group, the 2 mm group expressed more ferroptosis-related genes. Morphological changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7, the mitochondria in both groups shrank and the vacuoles became larger; on day 30, the mitochondria in the 1 mm group became larger, and the vacuoles in the 2 mm group remained enlarged. By analyzing the proportion of mitochondrial subgroups in different groups, we found that the model mice had different patterns of mitochondrial composition at different time periods, suggesting that the difference in the degree of damage among traumatic brain injury groups may reflect the mitochondrial changes. Taken together, differences in mitochondrial morphology and function between the 1 and 2 mm groups provide a new direction for the accurate classification of traumatic brain injury. Our results provide reliable data support and evaluation methods for promoting the establishment of standard mouse controlled cortical impingement model guidelines.

Out-of-Level Cognitive Testing of Children with Special Educational Needs

Abstract: Children with special educational needs in the area of learning (SEN-L) have severe learning disabilities and often exhibit substantial cognitive impairments. Therefore, standard assessment instruments of basic cognitive abilities designed for regular school children are frequently too complex for them and, thus, unable to provide reliable proficiency estimates. The present study evaluated whether out-of-level testing with the German version of the Cognitive Abilities Test using test versions developed for younger age groups might suit the needs of these children. Therefore, N = 511 children with SEN-L and N = 573 low achieving children without SEN-L attending fifth grades in Germany were administered four tests measuring reasoning and verbal comprehension that were designed for fourth graders. The results showed that children with SEN-L exhibited significantly more missing responses than children without SEN-L. Moreover, three of the four tests were still too difficult for them. Importantly, no substantial differential response functioning was found for children with and without SEN-L. Thus, out-of-level testing might represent a feasible strategy to assess basic cognitive functioning in children with SEN-L. However, comparative interpretations would require additional norms or linked test versions that place results from out-of-level tests on a common metric.

Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology.

0762 Baseline characteristics: Solriamfetol’s effect on cognitive Health in Apnea participants during a Randomized Placebo-controlled study (SHARP)

Abstract Introduction Patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) may experience cognitive impairment. Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor approved in the US and EU to treat EDS associated with OSA. The objective of this study is to assess whether solriamfetol reduces cognitive impairment in patients with EDS associated with OSA. Methods This phase 4, randomized, double-blind, placebo-controlled, crossover trial (NCT04789174) is enrolling adults with OSA and associated EDS (Epworth Sleepiness Scale score >10) and impaired cognitive function defined by an age-adjusted scaled score ≤8 on the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) Coding subtest and a score ≥9 on the British Columbia–Cognitive Complaints Inventory (BC-CCI). Participants are randomized (1:1) to 2 weeks of placebo or solriamfetol (75 mg/day for 3 days, then 150 mg/day) during treatment period 1. After a 1-week washout, participants crossover to receive 2 weeks of the opposite treatment during treatment period 2. Assessments at baseline and after each treatment period include Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding administered 2, 4, 6, and 8 hours post-dose and the BC-CCI. The primary endpoint is change from baseline after each treatment period in the average of 2- and 4-hour post-dose RBANS Coding scores. A secondary endpoint is change from baseline after each treatment period in BC-CCI score. Target enrollment range is 116‒164 participants, pending interim analysis. Enrollment is ongoing; baseline characteristics to date are reported. Results As of October 20th, 2021, 33 participants have been randomized across 20 study sites in North America and Europe. In the intent-to-treat population to date (n=33), mean±SD age is 53.0±10.4, mean±SD BMI is 31.6±4.5, 64% are male, 70% are White (Black or African American, 24%; Asian, 6%), and most (91%) are not Hispanic or Latino. The mean±SD WAIS-IV Coding subtest age-correct scaled score is 6.7±1.3 at baseline, which is below previously observed scores in healthy individuals. Conclusion This ongoing study is the first to examine solriamfetol’s impact on cognitive impairment in participants with OSA. Participants enrolled to date reflect the typical demographics of patients with OSA and demonstrate substantial cognitive impairment. Support (If Any) Jazz Pharmaceuticals

Neuropsychological Performance Among Individuals at Clinical High-Risk for Psychosis vs Putatively Low-Risk Peers With Other Psychopathology: A Systematic Review and Meta-Analysis.

Youth at clinical high-risk (CHR) for psychosis present with neuropsychological impairments relative to healthy controls (HC), but whether these impairments are distinguishable from those seen among putatively lower risk peers with other psychopathology remains unknown. We hypothesized that any excess impairment among CHR cohorts beyond that seen in other clinical groups is minimal and accounted for by the proportion who transition to psychosis (CHR-T). We performed a systematic review and meta-analysis of studies comparing cognitive performance among CHR youth to clinical comparators (CC) who either sought mental health services but did not meet CHR criteria or presented with verified nonpsychotic psychopathology. Twenty-one studies were included representing nearly 4000 participants. Individuals at CHR showed substantial cognitive impairments relative to HC (eg, global cognition: g = -0.48 [-0.60, -0.34]), but minimal impairments relative to CC (eg, global cognition: g = -0.13 [-0.20, -0.06]). Any excess impairment among CHR was almost entirely attributable to CHR-T; impairment among youth at CHR without transition (CHR-NT) was typically indistinguishable from CC (eg, global cognition, CHR-T: g = -0.42 [-0.64, -0.19], CHR-NT: g = -0.09 [-0.18, 0.00]; processing speed, CHR-T: g = -0.59 [-0.82, -0.37], CHR-NT: g = -0.12 [-0.25, 0.07]; working memory, CHR-T: g = -0.42 [-0.62, -0.22], CHR-NT: g = -0.03 [-0.14, 0.08]). Neurocognitive impairment in CHR cohorts should be interpreted cautiously when psychosis or even CHR status is the specific clinical syndrome of interest as these impairments most likely represent a transdiagnostic vs psychosis-specific vulnerability.

Serum Thioredoxin-80 is associated with age, ApoE4, and neuropathological biomarkers in Alzheimer\u2019s disease: a potential early sign of AD

BackgroundThioredoxin-80 (Trx80) is a cleavage product from the redox-active protein Thioredoxin-1 and has been previously described as a pro-inflammatory cytokine secreted by immune cells. Previous studies in our group reported that Trx80 levels are depleted in Alzheimer’s disease (AD) brains. However, no studies so far have investigated peripheral Trx80 levels in the context of AD pathology and whether could be associated with the main known AD risk factors and biomarkers.MethodsTrx80 was measured in serum samples from participants from two different cohorts: the observational memory clinic biobank (GEDOC) (N = 99) with AD CSF biomarker data was available and the population-based lifestyle multidomain intervention trial Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (N = 47), with neuroimaging data and blood markers of inflammation available. The GEDOC cohort consists of participants diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and AD, whereas the FINGER participants are older adults at-risk of dementia, but without substantial cognitive impairment. One-way ANOVA and multiple comparison tests were used to assess the levels of Trx80 between groups. Linear regression models were used to explore associations of Trx80 with cognition, AD CSF biomarkers (Aβ42, t-tau, p-tau and p-tau/t-tau ratio), inflammatory cytokines, and neuroimaging markers.ResultsIn the GEDOC cohort, Trx80 was associated to p-tau/t-tau ratio in the MCI group. In the FINGER cohort, serum Trx80 levels correlated with lower hippocampal volume and higher pro-inflammatory cytokine levels. In both GEDOC and FINGER cohorts, ApoE4 carriers had significantly higher serum Trx80 levels compared to non-ApoE4 carriers. However, Trx80 levels in the brain were further decreased in AD patients with ApoE4 genotype.ConclusionWe report that serum Trx80 levels are associated to AD disease stage as well as to several risk factors for AD such as age and ApoE4 genotype, which suggests that Trx80 could have potential as serum AD biomarker. Increased serum Trx80 and decreased brain Trx80 levels was particularly seen in ApoE4 carriers. Whether this could contribute to the mechanism by which ApoE4 show increased vulnerability to develop AD would need to be further investigated.Trial registrationClinicalTrials.govNCT01041989. Registered on 4 January 2010—retrospectively registered

Brain amyloid load and cognitive trajectories in older individuals at risk for dementia

AbstractBackgroundMost studies have so far investigated the cognitive performances and amyloid status on brain PET scans in cognitively normal, cognitively impaired, or individuals with dementia. In this study associations between brain amyloid status and changes in cognitive performance over time in an at‐risk older general population without dementia or substantial cognitive impairment were evaluated.MethodForty‐eight individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in the 11C‐Pittsburgh compound B (PiB)‐positron emission tomography (PET) exploratory sub‐study. Participants were categorized as amyloid+ or amyloid– after baseline PET scans were assessed visually by two experienced readers. A comprehensive cognitive Neuropsychological Test Battery (NTB) was used to assess cognitive performance at baseline, 12‐ and 24‐month follow‐up. The Prospective and Retrospective Memory Questionnaire was used to measure subjective cognitive complaints (SCCs) during the study. Changes in cognitive functions during the 2‐year study were compared across baseline amyloid groups using mixed effects regression models with maximum likelihood estimation.ResultThe mean age for all participants (n=48) was 71.4 years, and 22 participants (45%) were female. At baseline, 20 participants (42%) had amyloid+ PET scans and amyloid positivity was associated with lower NTB executive function (estimate = ‐0.38, 95% CI= ‐0.70 – ‐0.05, p=0.03). Interaction terms between baseline amyloid+ status and time were significant for NTB total score (estimate=‐0.10, 95% CI= ‐0.20 – ‐0.01, p=0.04) and NTB memory score (estimate = ‐0.18, 95% CI= ‐0.34 – ‐0.03, p=0.02). No significant associations were observed between amyloid positivity and change in NTB executive function score or NTB processing speed score. Furthermore, amyloid status was not significantly related to SCCs.ConclusionResults from this study suggest that positive amyloid status is likely to reduce cognitive abilities over time. Interestingly, in this very early at‐risk stage before the onset of substantial impairment or dementia, amyloid status was related to poorer trajectories in global cognition and memory over time, but not to subjective cognitive complaints. However, future studies with larger sample sizes and longer follow up period will be needed to further investigate the impact of amyloid accumulation.

Parenting Stress, Self-Efficacy, and Involvement: Effects on Spoken Language Ability Three Years After Cochlear Implantation.

This study evaluated associations among parenting stress, self-efficacy, and involvement in relation to spoken language outcomes in young children 3 years following cochlear implantation. Cross-sectional. Six university tertiary medical centers. One hundred sixty-four young children with bilateral, severe-to-profound sensorineural hearing loss who had 3 years of experience with a CI; children with substantial cognitive impairments were excluded from the study. Family Stress Scale (FSS), Scale of Parental Involvement and Self-Efficacy (SPISE), Oral and Written Language Scales (OWLS). Correlations were of moderate strength between FSS scores and SPISE scores (Parental Self-Efficacy, r = -0.45, p < 0.01, Parental Involvement r = -0.32, p < 0.01). As hypothesized, parents reporting higher levels of stress reported lower perceptions of self-efficacy and involvement. In addition, results showed that family stress had a direct, negative effect on spoken language (-4.43 [95% confidence interval: -6.97; -1.89]). After controlling for maternal education and activation age, parental self-efficacy mediated the negative effect between family stress and spoken language (indirect effect = -1.91 [3.45; -0.69]; proportion mediated = 0.43). No mediating effects were found for parental involvement. These findings highlight the need for parenting interventions that focus on reducing stressors and increasing parents' perceptions of self-efficacy in families of children using cochlear implants. Integration of mental health screening and tailored parenting interventions in CI clinics may increase parental self-efficacy and involvement, with measurable benefits in the child's use of spoken language.

Cognitive assessment for older adults with cancer: A Young International Society of Geriatric Oncology and Nursing & Allied Health Interest Group initiative

Cancer is a disease that mostly affects older adults around the world and the incidence is expected to increase further due to the aging of the world population [ [1] Pilleron S. Sarfati D. Janssen-Heijnen M. et al. Global cancer incidence in older adults, 2012 and 2035: a population-based study. Int J Cancer. 2019; 144: 49-58 Crossref PubMed Scopus (162) Google Scholar ]. Cognitive impairment is also common in the older adult population, and can span in severity from Mild Cognitive Impairment (MCI) to dementia. Dementia is a prevalent condition, occurring in 5–7% in older adults aged 60 years and older and this prevalence is also expected to increase due to the aging of the population [ [2] Prince M. Bryce R. Albanese E. Wimo A. Ribeiro W. Ferri C.P. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013; 9 (63–75.e62) Abstract Full Text Full Text PDF Scopus (2840) Google Scholar ]. Dementia, also referred to as major neurocognitive disorder in the DSM-5, is diagnosed when an older adult has substantial cognitive impairment in one or more cognitive domains that interferes with independence in daily activities [ [3] Brodaty H. Aerts L. Crawford J.D. et al. Operationalizing the diagnostic criteria for mild cognitive impairment: the salience of objective measures in predicting incident dementia. Am J Geriatr Psychiatry. 2017; 25: 485-497 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ]. Whereas, MCI is an early stage of memory loss that is defined as: a) a cognitive complaint or concern, ideally corroborated by an informant, b) objective evidence of cognitive impairment that is abnormal for their age on standardized testing (usually defined as 1–2 standard deviations below normal on the test used); and c) no significant impact on function [ [3] Brodaty H. Aerts L. Crawford J.D. et al. Operationalizing the diagnostic criteria for mild cognitive impairment: the salience of objective measures in predicting incident dementia. Am J Geriatr Psychiatry. 2017; 25: 485-497 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ]. There is no clear data on how many older adults with MCI develop dementia as rates vary between clinical and population samples, but reversal to normal function is also possible [ [3] Brodaty H. Aerts L. Crawford J.D. et al. Operationalizing the diagnostic criteria for mild cognitive impairment: the salience of objective measures in predicting incident dementia. Am J Geriatr Psychiatry. 2017; 25: 485-497 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ]. MCI incidence varies widely but meta-analyses showed ranges per 1000 person-years from 22.5 (5.1–51.4) for ages 75-79y, 40.9 (7.7–97.5) for ages 80-84y, to 60.1 (6.7–159.0) for ages 85 and older [ [4] Gillis C. Mirzaei F. Potashman M. Ikram M.A. Maserejian N. The incidence of mild cognitive impairment: a systematic review and data synthesis. Alzheimers Dement (Amst). 2019; 11: 248-256 Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar ]. In older adults with pre-existing MCI or dementia who are subsequently diagnosed with cancer, cognitive impairment can lead to challenges in cancer care, including later diagnosis, receive less treatment, having more complications during their cancer treatment and have shorter cancer survival [ [5] Hopkinson J.B. Milton R. King A. Edwards D. People with dementia: what is known about their experience of cancer treatment and cancer treatment outcomes? A systematic review. Psychooncology. 2016; 25: 1137-1146 Crossref PubMed Scopus (26) Google Scholar ]. A prior study using the Surveillance, Epidemiology and End Results (SEER) database reported a prevalence of precancer diagnosis of dementia of 7.4% in patients with breast cancer, 10.0% for colon cancer, and 5.1% for prostate cancer [ [6] Raji M.A. Kuo Y.F. Freeman J.L. Goodwin J.S. Effect of a dementia diagnosis on survival of older patients after a diagnosis of breast, colon, or prostate cancer: implications for cancer care. Arch Intern Med. 2008; 168: 2033-2040 Crossref PubMed Scopus (96) Google Scholar ].

Prefrontal cortex alterations in major depressive disorder, generalized anxiety disorder and their comorbidity during a verbal fluency task assessed by multi-channel near-infrared spectroscopy

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid with each other, and both associated with substantial cognitive impairments; however, it is still unclear whether their impairments are neurobiologically similar or distinct. This study aims to investigate the cognitive functions of the prefrontal cortex (PFC) in patients with MDD and GAD during the verbal fluency task (VFT) using functional near-infrared spectroscopy (fNIRS). Fifty-two patients with MDD, fifty-one patients with GAD, fifty-two patients with the comorbidity of MDD and GAD (CMG), and forty-seven healthy controls (HC) participated in the study. Significant hypoactivation in the left ventrolateral and the left dorsolateral PFC was common in all patient groups when compared to HCs, suggesting a shared etiology. Furthermore, MDD patients showed significant hypoactivation at the right frontal pole cortex (FPoC) when compared to HCs and significant hypoactivation at the middle FPoC when compared to the CMG patients. Our work is the first fNIRS study to reveal the shared and unique neurobiological profiles of MDD, GAD and their comorbidity under the same standard experimentation condition, suggesting fNIRS holds promise as an adjutant to assist clinical diagnosis.

Challenges to Understanding the Role of Cognition in the Assessment of Activities of Daily Living in Patients with Spinal Cord Injury: A Narrative Literature Review

<h3>Research Objectives</h3> When working in acute rehabilitation settings with physically compromised populations, including patients with spinal cord injury (SCI), assessing one's ability to manage basic and instrumental activities of daily living (ADLs) is a crucial component of treatment and discharge planning. Neurocognitive diagnoses, in particular, are predicated on the extent to which one's cognitive deficits negatively impact ADLs. However, parsing apart the relative contribution of cognitive versus physical changes on ADLs can be particularly challenging in patients with SCI as decline in ADLs may be attributable to motor limitations, cognitive decline, or both. This narrative review sought to investigate the existing literature regarding cognitive assessment and the role of cognition in functional assessment in SCI <h3>Design</h3> Narrative literature review. <h3>Setting</h3> N/A. <h3>Participants</h3> N/A. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> N/A. <h3>Results</h3> Robust empirical data suggest substantial cognitive impairment in individuals with SCI. However, there is a lack of standardized cognitive assessments designed for use specifically with this population. Further, few studies have been published assessing the role of cognition in functional assessment of patients post-SCI, and those reviewed suggest that current functional measures with cognitive components have limited ecological validity. This can ultimately result in a lack of convergence among one's cognitive status, motor limitations, and ability to function independently post-discharge. <h3>Conclusions</h3> While many of the existing measures of functional assessment in SCI speak to the general capacity of physical recovery and level of physical functioning post-injury, few address ability to resume daily activities following discharge from a cognitive perspective. This lack of inclusion of cognition in functional assessment presents challenges for rehabilitation psychologists and neuropsychologists in making accurate diagnoses and treatment plans while working with patients with new onset cognitive difficulties, particularly within the context of physical disability such as SCI. <h3>Author(s) Disclosures</h3> None.

Corticosteroids for COVID-19 symptoms and quality of life at 1 year from admission.

The long‐term evolution of COVID‐19 is unknown, making it necessary to study the persistence of symptoms over time and their impact on quality of life in people who have had the disease. We analyzed these aspects 1 year after admission for COVID‐19 and explored the influence of treatment with systemic corticosteroids during the acute phase of the illness. This observational cohort study took place in a tertiary hospital in March and April 2021 and included people admitted due to infection with SARS‐CoV‐2 in March, April, or May 2020. We excluded patients who had died, were unreachable or had substantial cognitive impairment. A telephone survey was undertaken to assess the presence of symptoms related to COVID‐19 and to administer the SF‐36 quality of life questionnaire. Other variables collected were demographic and clinical data along with the treatment received and the evolution over time. We analyzed 76 patients, including 44 who did not receive corticosteroids and 32 who did. Most symptoms were less frequent in the group that received corticosteroids, with statistically significant differences for headache, dysphagia, chest pain, and depression. These patients also showed significantly better outcomes in the SF‐36 domains for “bodily pain” and “mental health.” Corticosteroids administered in the acute phase of COVID‐19 could attenuate the presence of long‐term symptoms and improve patients’ quality of life.