Specific Cognitive Measures Research Articles

Polygenic hazard score predicts synaptic and axonal degeneration and cognitive decline in Alzheimer's disease continuum

BackgroundGrowth associated protein-43 (GAP-43) and neurofilaments light (NFL) are biomarkers of synaptic and axonal injury, and are associated with cognitive decline in Alzheimer's disease (AD) contiuum. We investigated whether Polygenic Hazard Score (PHS) is associated with specific biomarkers and cognitive measures, and if it can predict the relationship between GAP-43, NFL, and cognitive decline in AD. MethodWe enrolled 646 subjects: 93 with AD, 350 with mild cognitive impairment (MCI), and 203 cognitively normal controls. Variables included GAP-43, plasma NFL, and PHS. A PHS of 0.21 or higher was considered high risk while a PHS below this threshold was considered low risk. A subsample of 190 patients with MCI with four years of follow-up cognitive assessments were selected for longitudinal analysis . We assessed the association of the PHS with AD biomarkers and cognitive measures, as well as the predictive power of PHS on cognitive decline and the conversion of MCI to AD. ResultsPHS showed high diagnostic accuracy in distinguishing AD, MCI, and controls. At each follow-up point, high risk MCI patients showed higher level of cognitive impairment compared to the low risk group. GAP-43 correlated with all follow-up cognitive tests in high risk MCI patients which was not detected in low risk MCI patients. Moreover, high risk MCI patients progressed to dementia more rapidly compared to low risk patients. ConclusionPHS can predict cognitive decline and impacts the relationship between neurodegenerative biomarkers and cognitive impairment in AD contiuum. Categorizing patients based on PHS can improve the prediction of cognitive outcomes and disease progression.

A (mérsékelten rizikós) koraszülöttség az IQ hátrány ellenére nem akadályozza az olvasási és helyesírási képességek fejlődését

Background and aims: It is well established that the impacts of prematurity are often long-lasting in the various domains of development, however, the published findings concerning the prevalence, severity, and background of disorders are inconsistent. As yet research into the development of abilities contributing to the academic progress in Hungarian preterm children has been scarce. Our study aimed to find out to what extent prematurity impeded the reading and spelling abilities in school age and to contribute some information on the cognitive background of the performances. Methods: Three groups of 7 – 12 year-old children participated in the study. The target group consisted of moderate-risk preterms. For comparison two groups of full-term children were tested: typically developing good readers and dyslexics. To assess the reading and spelling abilities the Hungarian version of the 3DM (Dyslexia Differential Diagnosis) was used. Cognitive abilities were assessed using the Hungarian adaptation of the WISC-IV and the Rey Complex Figure Test. Results: The reading and spelling performances of the full-term good readers and the preterms did not differ and the preterms scored higher than the dyslexics. The cognitive tests did not offer any direct explanation to this, since the preterms lagged behind the full-term good readers in the WISC-IV full-scale IQ as well as in several specific cognitive measures. The CART Decision Tree served to analyse the relationships, allowing to reveal the interactions and the moderation effects. Discussion: The CHC model as a theoretical framework and the CART Decision Tree statistical analysis proved to be fruitful to disentangle the complex interplay of the cognitive background factors. There are various cognitive paths of acquiring the reading and spelling skills, e.g., in case of relatively lower IQs the sufficient levels of memory and processing speed may ensure success.

Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer's disease, Alzheimer's disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis.

We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer's disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment. Systematic review, Meta-Analysis. We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023. RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included. Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423). The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer's Disease Assessment Scale-Cognitive Subscale (SMD = -0.96 [-1.32, -0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity. The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Effects of photon irradiation in the presence and absence of hindlimb unloading on the behavioral performance and metabolic pathways in the plasma of Fischer rats.

Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures. Methods: A total of 344 male Fischer rats were irradiated with photons (6MeV; 3, 8, or 10Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses. Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3Gy, six metabolites were related to behavioral and cognitive measures. Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.

Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.

The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

The Association of Allergy-Related and Non-Allergy-Related Olfactory Impairment with Cognitive Function in Older Adults: Two Cross- Sectional Studies.

Evidence on the association of Olfactory Impairment (OI) with age-related cognitive decline is inconclusive, and the potential influence of allergy remains unclear. We aimed to evaluate the cross-sectional associations of allergy-related and non-allergy- related OI to cognitive function. We included 2,499 participants from the Health and Retirement Study (HRS)-Harmonized Cognitive Assessment Protocol (HCAP) sub-study and 1,086 participants from the English Longitudinal Study of Ageing (ELSA)-HCAP. The Olfactory Function Field Exam (OFFE) using Sniffin' Stick odor pens was used to objectively assess olfactory function and an olfactory score <6/11 indicated OI. Mini-Mental Status Examination (MMSE) was used to assess global cognitive function and define cognitive impairment (<24/30). A neuropsychologic battery was used to assess five cognitive domains. Compared to non-OI participants, individuals with OI had lower MMSE z-score [βHRS = -0.33, 95% Confidence Interval (CI): -0.41 to -0.24; βELSA = -0.31, -0.43 to -0.18] and higher prevalence of cognitive impairment (Prevalence Ratio (PR)HRS = 1.46, 1.06 to 2.01; PRELSA = 1.63, 1.26 to 2.11). The associations were stronger for non-allergy-related OI (βHRS = -0.36; βELSA = -0.34) than for allergy-related OI (βHRS = -0.26; βELSA = 0.13). Similar associations were observed with domain- specific cognitive function measures. OI, particularly non-allergy-related OI, was related to poorer cognitive function in older adults. Although the current cross-sectional study is subject to several limitations, such as reverse causality and residual confounding, the findings will provide insights into the OI-cognition association and enlighten future attention to non-allergy-related OI for the prevention of potential cognitive impairment.

Integrating Nutrient Biomarkers, Cognitive Function, and Structural MRI Data to Build Multivariate Phenotypes of Healthy Aging

BackgroundResearch in the emerging field of nutritional cognitive neuroscience demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect cognitive performance and brain health. ObjectivesAlthough previous research has primarily examined the bivariate relationship between nutrition and cognition or nutrition and brain health, this study sought to investigate the joint relationship between these essential and interactive elements of human health. MethodsWe applied a state-of-the-art data fusion method, coupled matrix tensor factorization, to characterize the joint association between measures of nutrition (52 nutrient biomarkers), cognition (Wechsler Abbreviated Test of Intelligence and Wechsler Memory Scale), and brain health (high-resolution MRI measures of structural brain volume) within a cross-sectional sample of 111 healthy older adults, with an average age of 69.1 y, 62% being female, and an average body mass index of 26.0 kg/m2. ResultsData fusion uncovered latent factors that capture the joint association between specific nutrient profiles, cognitive measures, and cortical volumes, demonstrating the respects in which these health domains are coupled. A hierarchical cluster analysis further revealed systematic differences between a subset of variables contributing to the underlying latent factors, providing evidence for multivariate phenotypes that represent high and low levels of performance across multiple health domains. The primary features that distinguish between each phenotype were as follows: 1) nutrient biomarkers for monounsaturated and polyunsaturated fatty acids; 2) cognitive measures of immediate, auditory, and delayed memory; and 3) brain volumes within frontal, temporal, and parietal cortexes. ConclusionsBy incorporating innovations in nutritional epidemiology (nutrient biomarker analysis), cognitive neuroscience (high-resolution structural brain imaging), and statistics (data fusion), this study provides an interdisciplinary synthesis of methods that elucidate how nutrition, cognition, and brain health are integrated through lifestyle choices that affect healthy aging.

Association between inflammation and cognition: Triangulation of evidence using a population-based cohort and Mendelian randomization analyses

BackgroundInflammation is associated with cognitive functioning and dementia in older adults, but whether inflammation is related to cognitive functioning in youth and whether these associations are causal remains unclear. MethodsIn a population-based cohort (Avon Longitudinal Study of Parents and Children; ALSPAC), we investigated cross-sectional associations of inflammatory markers (C-reactive protein [CRP], Interleukin-6 [IL-6] and Glycoprotein acetyls [GlycA]) with measures of cold (working memory, response inhibition) and hot (emotion recognition) cognition at age 24 (N = 3,305 in multiple imputation models). Furthermore, we conducted one-sample and two-sample bidirectional Mendelian randomization (MR) analyses to examine potential causal effects of genetically-proxied inflammatory markers (CRP, GlycA, IL-6, IL-6 receptor, soluble IL-6 receptor) on cognitive measures (above) and on general cognitive ability. ResultsIn the ALSPAC cohort, there was limited evidence of an association between standardised inflammatory markers and standardised cognitive measures at age 24 after adjusting for potential confounders (N = 3,305; beta range, −0.02 [95 % confidence interval (CI) −0.06 to 0.02, p = 0.27] to 0.02 [95 % CI −0.02 to 0.05, p = 0.33]). Similarly, we found limited evidence of potential effects of 1-unit increase in genetically-proxied inflammatory markers on standardised working memory, emotion recognition or response inhibition in one-sample MR using ALSPAC data (beta range, −0.73 [95 % CI −2.47 to 1.01, p = 0.41] to 0.21 [95 % CI −1.42 to 1.84, p = 0.80]; or on standardised general cognitive ability in two-sample MR using the latest Genome-Wide Association Study (GWAS) datasets (inverse-variance weighted beta range, −0.02 [95 % CI −0.05 to 0.01, p = 0.12] to 0.03 [95 % CI −0.01 to 0.07, p = 0.19]). ConclusionsOur MR findings do not provide strong evidence of a potential causal effect of inflammatory markers (CRP, IL-6, IL-6 receptor, GlycA) on the cognitive functions examined here. Given the large confidence intervals in the one-sample MR, larger GWAS of specific cognitive measures are needed to enable well-powered MR analyses to investigate whether inflammation causally influences specific cognitive domains.

Classification of Alzheimer's disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: A cross sectional observational study.

Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region. This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.

Cognitive mechanisms underlying decision making involving risk of explicit punishment in male and female rats.

Individuals engage in the process of risk-based decision making on a daily basis to navigate various aspects of life. There are, however, individual differences in this form of decision making, with some individuals exhibiting preference for riskier choices (risk taking) and others exhibiting preference for safer choices (risk aversion). Recent work has shown that extremes in risk taking (e.g., excessive risk taking or risk aversion) are not only cognitive features of neuropsychiatric diseases, but may in fact predispose individuals to the development of such diseases. To better understand individual differences in risk taking, and thus the mechanisms by which they confer disease vulnerability, the current study investigated the cognitive contributions to risk taking in both males and females. Rats were first behaviorally characterized in a decision-making task involving risk of footshock punishment and then tested on a battery of cognitive behavioral assays. Individual variability in risk taking was compared with performance on these tasks. Consistent with prior work, females were more risk averse than males. With the exception of the Set-shifting Task, there were no sex differences in performance on other cognitive assays. There were, however, sex-dependent associations between risk taking and specific cognitive measures. Greater risk taking was associated with better cognitive flexibility in males whereas greater risk aversion was associated with better working memory in females. Collectively, these findings reveal that distinct cognitive mechanisms are associated with risk taking in males and females, which may account for sex differences in this form of decision making.

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition

Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d=0.61), and these improvements were sustained in the continuation phase. This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

Are Adverse Childhood Experiences Associated with Worse Cognitive Function in Older Adults?

Adverse childhood experiences (ACE) are associated with an increased risk for dementia, but this relationship and modifying factors are poorly understood. This study is the first to our knowledge to comprehensively examine the effect of ACE on specific cognitive functions and measures associated with greater risk and resiliency to cognitive decline in independent community-dwelling older adults. Verbal/nonverbal intelligence, verbal memory, visual memory, and executive attention were assessed. Self-report measures examined depression, self-efficacy, and subjective cognitive concerns (SCC). The ACE questionnaire measured childhood experiences of abuse, neglect, and household dysfunction. Over 56% of older adults reported an adverse childhood event. ACE scores were negatively associated with income and years of education and positively associated with depressive symptoms and SCC. ACE scores were a significant predictor of intellectual function and executive attention; however, these relationships were no longer significant after adjusting for education. Follow-up analyses using the PROCESS macro revealed that relationships among higher ACE scores with intellectual function and executive attention were mediated by education. Greater childhood adversity may increase vulnerability for cognitive impairment by impacting early education, socioeconomic status, and mental health. These findings have clinical implications for enhancing levels of cognitive reserve and addressing modifiable risk factors to prevent or attenuate cognitive decline in older adults.

Profiles of Cognitive Change in Preclinical and Prodromal Alzheimer's Disease Using Change-Point Analysis.

Alzheimer's disease (AD) is now understood to have a long preclinical phase in which pathology starts to accumulate in the absence of clinical symptoms. Identifying the temporal stages of accelerated cognitive decline in this phase may help in developing more sensitive neuropsychological tools for early screening of preclinical cognitive decline. Change-point analyses are increasingly used to characterize the temporal stages of accelerated cognitive decline in the preclinical stages of AD. However, statistical comparisons of change-points between specific cognitive measures have not been reported. To characterize and compare the temporal stages of accelerated decline in performance on multiple cognitive tests in a sample of participants from the Baltimore Longitudinal Study on Aging (BLSA) who later developed AD. 165 older adults (baseline age range: 61.1-91.2) from the BLSA developed AD during follow-up. Linear and non-linear mixed models were fit for 11 cognitive measures to determine change-points in rates of decline before AD diagnosis. Bootstrapping was used to compare the timing of change-points across cognitive measures. Change-points followed by accelerated decline ranged from 15.5 years (Standard Error (S.E.) = 1.72) for Card Rotations to 1.9 years (S.E. = 0.68) for the Trail-Making Test Part A before AD diagnosis. Accelerated decline in Card Rotations occurred significantly earlier than all other measures, including learning and memory measures. Results suggest that visuospatial ability, as assessed by Card Rotations, may have the greatest utility as an early predictive tool in identifying preclinical AD.

A double-blind placebo-controlled clinical trial testing the effect of hyperbaric oxygen therapy on brain and cognitive outcomes of mildly cognitively impaired elderly with type 2 diabetes: Study design.

IntroductionType 2 diabetes (T2D) is a risk factor for dementia. Ischemia due to vascular pathology is hypothesized to be an underlying mechanism for this association. Hyperbaric oxygen therapy (HBOT) is a treatment in which oxygen‐enriched air (up to 100%) is administered to patients in a chamber at a pressure above one atmosphere absolute. HBOT is approved for the treatment of T2D ischemic non‐healing wounds. Evidence from animal studies and small clinical trials suggests that HBOT improves hypoxic/ischemic brain injuries, consequently inducing brain angiogensis, leading to cognitive improvement.MethodsWe present the design of the first double‐blind, placebo‐controlled, clinical trial on brain and cognitive outcomes in elderly (n = 154) with T2D and mild cognitive impairment to compare the effects of HBOT versus sham (normal air with 1.1 ATA pressure in the first and last 5 minutes of the session). Eligible candidates are randomized with equal probability to HBOT and sham. Outcomes are assessed before and after treatment, and at 6‐ and 12‐month follow‐up. The primary cognitive outcome is global cognitive change, indexed by a composite sum of z‐scores of four executive functions and four episodic memory tests. The primary neurobiological outcome is cerebral blood flow (CBF; via arterial spin labeling magnetic resonance imaging [ASL‐MRI]) and cerebral glucose utilization via fluorodeoxyglucose positron emission tomography (FDG‐PET). Secondary outcome measures are specific cognitive domains (executive function and episodic memory) and functional measures (Clinical Dementia Rating sum of boxes, activities of daily living). Efficacy analyses will be performed for the intent‐to‐treat sample.DiscussionRecent studies suggest that HBOT induces neuroplasticity and improves cognition in post‐stroke and traumatic brain injury patients. However, its effect on cognition, cerebral blood flow, and brain glucose utilization in T2D patients at high dementia risk is yet to be determined. If effective, this study may provide strong evidence for the brain and cognitive benefits of HBOT in this population.

Attitudes About Cognitive Screening: A Survey of Home Care Physical Therapists

Home care physical therapists (PTs) are inconsistent regarding cognitive screening, possibly because screening tools were traditionally considered the domain of other home care disciplines, or because therapists perceive their dementia training to be inadequate. A cross sectional study was designed to survey home care therapists' attitudes and beliefs about the management of persons with dementia and to find out whether any specific cognitive tools or measures are currently used. A 5-point Likert-type survey was administered to home care PTs via an online survey. Three state home care associations and individual home care agencies agreed to share the survey link. The survey was also made available to American Physical Therapy Association members through the Home Health and Geriatric Section listservs. Two hundred fifty-one PTs opened the survey and 233 completed the survey. Respondents included 180 females and 53 males. Seventy-four had a bachelor's degree (BS), 53 held a master's degree (MS), 104 had achieved a doctor of physical therapy (DPT) or doctor of philosophy (PhD) degree, and 2 did not provide this information. Significant differences were found between those with the highest doctoral degrees and those with master's or bachelor's degrees (P = .01) regarding whether they were qualified to screen (strongly agree, agree) for cognitive deficits. Therapists with the highest degrees also attended continuing education for dementia training more than those with less formal education (P = .042.) Gender differences were found in 2 questions regarding positive outcomes (P = .010 and .42); for both questions, males were more likely to believe that dementia has a negative impact. Eighty-seven percent indicated that PTs are qualified (strongly agree, agree), but only 53% said that they possess the necessary skills (strongly agree, agree) to perform cognitive screens. Specialty certification revealed significant differences in several of the questions. No significance was found for any question regarding years of practice or years in home care. The Mini-Mental State Examination and the Clock Drawing Test were most frequently cited among PTs who conduct cognitive screening. Physical therapists recognize that they are qualified to perform cognitive screening but may need additional training to utilize cognitive findings to enhance interventions and outcomes in home care. More research is needed to determine which screens are most relevant for therapist use and to examine the effect of cognitive screening on therapy outcomes.

Cognitive functioning and quality of life: Diverging views of older adults with Alzheimer and professional care staff.

Staff ratings of quality of life (QOL) in dementia are often lower and more strongly related to the cognitive functioning of the person with dementia than self-ratings. However, cognition-related items in QOL measures and limited cognitive screening measures hamper a clear understanding of the relationship, 2 issues we addressed in the current study. We collected data of 88 pairs of older adults with Alzheimer disease and their professional caregivers in 9 residential care settings. Both self-report and staff report of the QOL of residents were assessed with the Quality of Life in Alzheimer's Disease. Cognitive functioning was assessed with the Mini-Mental State Examination and a battery of specific cognitive measures. Intraclass correlations and a paired sample t test confirmed a discrepancy between self-rating and staff rating, with staff significantly underestimating QOL as experienced by the resident. After removing the possibly confounding memory item of the Quality of Life in Alzheimer's Disease, Mini-Mental State Examination score remained a significant predictor of staff ratings but not self-ratings in regression analyses. Exploratory analyses of specific cognitive measures showed a significant contribution of a memory test of intentional visual association learning in the prediction of staff-rated QOL. Staff reports cannot simply substitute reports of the subjective experience of residents with Alzheimer, so both judgments should be taken into account to form an adequate picture of QOL. Staff might be guided more strongly by a cognitive point of view when evaluating QOL of residents with Alzheimer disease, while the latter might have shifted their evaluation standards to cope adequately with the challenges posed by their disease.

Rethinking Functional Outcome Measures: The Development of a Novel Upper Limb Token Transfer Test to Assess Basal Ganglia Dysfunction.

The basal ganglia are implicated in a wide range of motor, cognitive and behavioral activities required for normal function. This region is predominantly affected in Huntington's disease (HD), meaning that functional ability progressively worsens. However, functional outcome measures for HD, particularly those for the upper limb, are limited meaning there is an imperative for well-defined, quantitative measures. Here we describe the development and evaluation of the Moneybox test (MBT). This novel, functional upper limb assessment was developed in accordance with translational neuroscience and physiological principles for people with a broad disease manifestation, such as HD. Participants with HD (n = 64) and healthy controls (n = 21) performed the MBT, which required subjects to transfer tokens into a container in order of size (Baseline Transfer), value (Complex Transfer) with and without reciting the alphabet (Dual Transfer). Disease specific measures of motor, cognition, behavior, and function were collected. HD patients were grouped into disease stage, from which, discriminative and convergent validity was assessed using Analysis of Variance and Pearson's correlation respectively. Manifest HD participants were slower than pre-manifest and control participants, and achieved significantly lower MBT total scores. Performance in the Complex Transfer and Dual Transfer tasks were significantly different between pre-manifest and stage 1 HD. All MBT performance variables significantly correlated with routinely used measures of motor, cognition, behavior, and function. The MBT provides a valid, sensitive, and affordable functional outcome measure. Unlike current assessments, MBT performance significantly distinguished the subtle differences between the earliest disease stages of HD, which are the populations typically targeted in clinical trials.

The Art Gallery Test: A Preliminary Comparison between Traditional Neuropsychological and Ecological VR-Based Tests.

Ecological validity should be the cornerstone of any assessment of cognitive functioning. For this purpose, we have developed a preliminary study to test the Art Gallery Test (AGT) as an alternative to traditional neuropsychological testing. The AGT involves three visual search subtests displayed in a virtual reality (VR) art gallery, designed to assess visual attention within an ecologically valid setting. To evaluate the relation between AGT and standard neuropsychological assessment scales, data were collected on a normative sample of healthy adults (n = 30). The measures consisted of concurrent paper-and-pencil neuropsychological measures [Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Color Trails Test (CTT)] along with the outcomes from the three subtests of the AGT. The results showed significant correlations between the AGT subtests describing different visual search exercises strategies with global and specific cognitive measures. Comparative visual search was associated with attention and cognitive flexibility (CTT); whereas visual searches involving pictograms correlated with global cognitive function (MoCA).

Cognitive Skills Training for Homeless Transition-Age Youth

Cognitive impairments are common in homeless youth and negatively impact academic and vocational outcomes. We examined the feasibility and efficacy of cognitive interventions provided to 18- to 22-year-old homeless youth living in urban supportive housing. Ninety-one homeless youth were randomized to receive either targeted cognitive training (cognitive remediation) or general cognitive activation (computer skills training). Cognitive and psychological outcomes were assessed at baseline, after 13 and 26 sessions, and 1 month postintervention. A high dropout rate highlighted the feasibility challenges of treating this population. Intent-to-treat analysis found significant improvements across groups in specific and global measures of cognition and psychological distress, with no significant group differences. Transition-age homeless youth show improvements in cognitive and psychological functioning when engaged in interventions that address their cognitive development. This speaks to the malleability of cognitive skills in this cohort and lays the groundwork for future research to address their cognitive health.

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

ObjectiveTo assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment.MethodsWe recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily), lithium (400 mg twice daily, titrated progressively), or remained in a control group (no new medication). The primary efficacy endpoint was change in a global cognitive score (NPZ-7). Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results.ResultsSeventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]): rivastigmine, 0.35 (0.14); lithium, 0.25 (0.40); control, 0.20 (0.44) (p = 0.78). The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48): rivastigmine, –0.47 (0.22) vs –0.11 (0.29), p = 0.06; lithium, –0.50 (0.40) vs –0.26 (0.21), p = 0.22; control, –0.52 (0.34) vs –0.32 (0.52), p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control): information processing speed, 0.35 (0.64) vs –0.13 (0.25), p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33) vs 0.03 (0.74), p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41%) individuals dropped out of the study: 2 (20%) were due to medication-related effects in the rivastigmine group and 4 (36%) in the lithium group. No severe adverse events were reported.ConclusionsThe results from this small randomized trial indicate that transdermal rivastigmine did not provide significant cognitive benefits in people with HAND on stable antiretroviral therapy, even though positive trends were found in specific cognitive domains. Relevant tolerability issues were not observed.