Processing Speed Tasks Research Articles

Processing speed impairment in chronic inflammatory demyelinating polyneuropathy patients: a cross-sectional study.

There is a lack of evidence of cognitive involvement in chronic inflammatory demyelinating polyneuropathy (CIDP) and, the reports about the involvement of the brain and central nervous system (CNS) are few and controversial. The Five Digit Test (FDT) evaluates processing speed (PS) and executive functions orally. To evaluate the performance on the FDT of CIDP patients with and without CNS (brain/cerebellum) alterations observed on brain Magnetic Resonance Imaging (MRI) scans. The Hospital Anxiety and Depression Scale (HADS, to assess neuropsychiatry symptoms), the Rasch-built Overall Disability Scale (R-ODS; to assess disability), and the FDT (to assess cognition) were applied to 14 CIDP patients and 24 age-matched healthy control subjects. The patients were submitted to routine brain MRI and, according to the results, they were divided into two groups: those with abnormalities on the MRI (CIDPabnl) and those with normal parameters on the MRI (CIDPnl). The FDT data of five CIDPnl patients and nine CIDPabnl subjects were analyzed. Comparisons between the groups were performed for each task of the FDT. We found statistical differences for both groups of CIDP patients in terms of PS, for the patients spent more time performing the PS tasks than the controls. The PS measures were negatively associated with disability scores (reading: r = -0.47; p = 0.003; counting: r = -0.53; p = 0.001). Our data suggested the presence of PS impairment in CIDP patients. Disability was associated with slow PS.

Accounting for retest effects in cognitive testing with the Bayesian double exponential model via intensive measurement burst designs.

Monitoring early changes in cognitive performance is useful for studying cognitive aging as well as for detecting early markers of neurodegenerative diseases. Repeated evaluation of cognition via a measurement burst design can accomplish this goal. In such design participants complete brief evaluations of cognition, multiple times per day for several days, and ideally, repeat the process once or twice a year. However, long-term cognitive change in such repeated assessments can be masked by short-term within-person variability and retest learning (practice) effects. In this paper, we show how a Bayesian double exponential model can account for retest gains across measurement bursts, as well as warm-up effects within a burst, while quantifying change across bursts in peak performance. We also highlight how this approach allows for the inclusion of person-level predictors and draw intuitive inferences on cognitive change with Bayesian posterior probabilities. We use older adults’ performance on cognitive tasks of processing speed and spatial working memory to demonstrate how individual differences in peak performance and change can be related to predictors of aging such as biological age and mild cognitive impairment status.

Associations of genetic liability for Alzheimer’s disease with cognition and eye movements in a large, population-based cohort study

To identify cognitive measures that may be particularly sensitive to early cognitive decline in preclinical Alzheimer’s disease (AD), we investigated the relation between genetic risk for AD and cognitive task performance in a large population-based cohort study. We measured performance on memory, processing speed, executive function, crystallized intelligence and eye movement tasks in 5182 participants of the Rhineland Study, aged 30 to 95 years. We quantified genetic risk for AD by creating three weighted polygenic risk scores (PRS) based on the genome-wide significant single-nucleotide polymorphisms coming from three different genetic association studies. We assessed the relation of AD PRS with cognitive performance using generalized linear models. Three PRS were associated with lower performance on the Corsi forward task, and two PRS were associated with a lower probability of correcting antisaccade errors, but none of these associations remained significant after correction for multiple testing. Associations between age and trail-making test A (TMT-A) performance were modified by AD genetic risk, with individuals at high genetic risk showing the strongest association. We conclude that no single measure of our cognitive test battery robustly captures genetic liability for AD as quantified by current PRS. However, Corsi forward performance and the probability of correcting antisaccade errors may represent promising candidates whose ability to capture genetic liability for AD should be investigated further. Additionally, our finding on TMT-A performance suggests that processing speed represents a sensitive marker of AD genetic risk in old age and supports the processing speed theory of age-related cognitive decline.

Effect of exposure to maternal diabetes during pregnancy on offspring’s brain cortical thickness and neurocognitive functioning

ABSTRACT Little is known about the long-term effects of maternal diabetes during pregnancy (DP), either gestational diabetes or preexisting diabetes (type 1 or type 2), on offspring’s brain morphometry and neurocognitive functioning (NCF). This study examined the effect of prenatal exposure to maternal DP on the brain structure and NCF in children between 9 and 10 years of age. This study used cross-sectional neuroimaging and NCF data from the baseline wave of the Adolescent Brain and Cognitive Development® study. Exposure to maternal DP was assigned from the developmental history questionnaire. Differences in the brain cortical thickness (CTh) and five cognitive abilities (executive function, working and episodic memory, processing speed, and language abilities) were examined in diabetes-exposed and diabetes-unexposed children. Linear mixed effect models and generalized linear models were used to adjust for the effect of confounding variables. A total of 9,967 children (718 diabetes-exposed and 9249 unexposed) were included in the analysis. Diabetes-exposed children had lower whole-brain CTh [mean: exposed vs unexposed = 2.725 mm vs 2.732 mm; difference (95%CI): −0.007 mm (−0.013, −0.001)] compared to unexposed children after adjusting for confounding variables. Diabetes-exposed children had lower CTh in most part of the occipital lobe of both hemispheres, right postcentral gyrus, and left superior parietal cortex. Diabetes-exposed children also had lower scores in processing speed task [mean difference (95%CI): −1.7 (−2.8, −0.6)] and total cognition [mean difference (95%CI): −0.6 (−1.2, −0.02)]. Diabetes-exposed children have reduced CTh and NCF during preadolescence, which might have implications for psychomotor development during later life. Prospective studies are needed to confirm our findings.

Childhood Maltreatment and Its Association with Cognitive Ability in Young People Suspected to Be at Clinical High Risk of Psychosis

Introduction: Childhood maltreatment is associated with both reduced cognitive functioning and the development of psychotic symptoms. However, the specific relationship between childhood maltreatment, cognitive abilities and (pre)psychotic symptoms remains unclear. Therefore, the aim of this study was to investigate the association between childhood maltreatment and tasks of verbal memory and processing speed in a help-seeking sample of an early detection of psychosis service. Methods: A total of 274 participants consisting of 177 clinical high risk (CHR) for psychosis subjects and 97 clinical controls (CC) with subthreshold CHR underwent a battery of neurocognitive assessments measuring the latent variables verbal memory and processing speed. Additionally, the Trauma and Distress Scale (TADS) was administered to assess varying childhood maltreatment subtypes. Structural equation modeling (SEM) was used to examine associations between verbal memory, processing speed, and maltreatment subtypes. Other factors in the model were age, gender, clinical group (CHR or CC), and the presence of different CHR criteria. Results: Physical abuse was associated with lower scores in verbal memory and processing speed. The explained variance in the SEM reached up to 9.5% for verbal memory and 24.9% for processing speed. Both latent variables were each associated with the presence of cognitive-perceptive basic symptoms. Lower verbal memory was additionally associated with the clinical high-risk group, and processing speed capacity was associated with higher age and female gender. Conclusion: Childhood physical abuse in particular was associated with poorer performance on verbal memory and processing speed across both groups of CHR and CC with subthreshold CHR symptoms. This adds to the current literature on reduced cognitive abilities when childhood maltreatment had occurred, albeit subtype dependent. Our findings, together with high prevalence rates of childhood maltreatment in patients with psychosis or CHR states, along with the presence of cognitive deficits in these patients, highlight the importance of not only assessing cognition but also childhood maltreatment in managing these patients. Future research should investigate the specific biological mechanisms of childhood maltreatment on verbal memory and processing speed in CHR subjects, as neurobiological alterations might explain the underlying mechanisms.

Neuropsychological profile of Turner Syndrome in relation to deficits in academic and psychosocial areas. A case report

Introduction Previous reviews reported an association between Turner Syndrome (TS) and a profile of deficits in some neurocognitive domains (visual-spatial domains, mathematics, and executive functions: cognitive flexibility, working memory, cognitive inhibition, and problem solving), although pointing out individual variability.ObjectivesTo describe the neuropsychological profile of a patient with diagnosis of TS and psychosocial difficulties attended at the Service of Psychiatry, Clinical Psychology and Mental Health at La Paz University Hospital (Madrid).MethodsA descriptive study is conducted on a single case of a 11-year-old woman with diagnosis of TS attended by a clinical psychologist at a child-adolescent Mental health center for social, family and academic difficulties. Neuropsychological assessment was completed in October, 2021. The Wechsler Intelligence Scale for Children-Five Edition (WISC-V) and Neuropsychological Assessment of Executive Functions in Children (ENFEN) batteries were administered.ResultsThe full-scale intelligence quotient was observed in the normal range, with lower scores in non-verbal tasks. Deficits (range from z = -2.00 to -1.75) were observed in tests of working memory, processing speed and complex problem-solving tasks. The results showed great variability in other executive functioning tasks (selective attention tasks: from z = -1.75 to -0.75; and cognitive flexibility tasks: from z = -2.25 to 0.25).ConclusionsThe neurocognitive profile described in the literature was partially consistent with the results obtained in this study. The neuropsychological assessment can support the elucidation of clinical diagnostic and therapeutic factors in TS patients with relevant psychosocial or cognitive difficulties.DisclosureNo significant relationships.

No clear associations between subjective memory concerns and subsequent change in cognitive function: the PATH through life study

The literature on subjective memory concerns (SMC) as a predictor for future cognitive decline is varied. Furthermore, recent research has pointed to additional complexity arising from variability in the experience of SMC themselves (i.e. whether they are remitting or sustained over time). We investigated the associations between SMC and objectively measured cognition in an Australian population-based cohort. Four waves (4-year intervals between waves) of data from 1236 participants (aged 62.4 ± 1.5 years, 53% male) were used. We categorized participants as experiencing SMC, when they indicated that their memory problems might interfere with their day-to-day life and/or they had seen a doctor about their memory. SMC was categorized as “no” reported SMC, “remitting”, “new-onset” or “sustained” SMC. Cognitive assessment of immediate and delayed recall, working memory, psychomotor speed, attention and processing speed were assessed using a neuropsychological battery. Eighteen percent of participants were characterised as having SMC: 6% (77) “remitting”, 6% (77) “new-onset” and 6% (69) “sustained” SMC. There was no consistent evidence for an association between SMC and subsequent decline in cognition. However, SMC was associated with poorer performance on contemporaneous tasks of attention and processing speed compared to “no” SMC. Asking about SMC may indicate a current decline in cognitive function but, in this sample at least, did not indicate an increased risk of future decline.

Association of Emerging β-Amyloid and Tau Pathology With Early Cognitive Changes in Clinically Normal Older Adults.

Alzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find the right test to optimize cognitive outcome measures for clinical trials. We sought to identify cognitive measures associated with the earliest detectable signs of emerging Aβ and tau pathology. One hundred twelve clinically normal adults with longitudinal Pittsburgh compound B (PiB)-PET, 18F-flortaucipir (FTP)-PET, and cognitive data for ≥7 years were included from the Harvard Aging Brain Study (HABS). Analyses assessed those initially classified as PiB- (less than Centiloid [CL] 20) and then expanded to include PiB+ individuals up to CL40, the approximate threshold beyond which neocortical tau proliferation begins. Separate linear mixed-effects models assessed the effects of emerging global Aβ (PiB slope) and tau (baseline FTP level and FTP slope) in the entorhinal and inferior temporal (IT) cortices on multiple cognitive tasks and the Preclinical Alzheimer's Cognitive Composite (PACC) over time. Steeper PiB slopes were associated with declining processing speed (Digit Symbol Substitution Test [DSST], Trail Making Test Part A) in those <CL20 and expanded to include learning/memory retrieval (FCSRT-FR], Selective Reminding Test Total Recall [SRT-tr], Logical Memory Immediate Recall) in the <CL40 group. FTP had limited effects under CL20, with only rising right IT FTP slope related to declining FCSRT-FR and SRT-tr learning/memory retrieval. When we expanded to include those initially <CL40, rising FTP level or slope was related to declines across all tasks, and PiB slope effects on memory retrieval but not DSST score were reduced. A composite measure of processing speed and memory retrieval tasks provided the strongest prediction of decline under CL40, while PACC score remained optimal at high levels of Aβ (>CL40). Early, Aβ-mediated cognitive slowing was detected for processing speed measures, while early memory retrieval declines were associated with emerging Aβ and tau pathology. Composites of these measures may help determine whether anti-Aβ or anti-tau therapies administered at the first signs of pathology might preserve cognitive function. This study provides Class I evidence that in clinically normal older adults, emerging PET-detected AD pathology is associated with declining processing speeds and memory retrieval.

Neuropsychological correlates of cerebellar volumes in multiple sclerosis: an MRI volumetric analysis study.

The hallmark of Multiple Sclerosis (MS) pathophysiology is the damage to the myelin sheath around axons. The cerebellum is a predilection site for demyelination with a well-recognized role in motor and a rather understudied contribution to cognitive functions. The aim of this study is to investigate patterns of cerebellar grey and white matter pathology, expressed as reduced volume, as well as cortical thickness and their potential contribution to cognitive performance and disability status of patients with MS. 24 patients with MS underwent extensive neuropsychological assessment using paper and pencil tests and the Brain Health Assessment (BHA) tablet-based battery. Cerebellar lobular volumes and thickness were calculated using a volumetric analysis with automated segmentation of the cerebellum and its lobules. The main findings are a reduction of cerebellar grey matter (CGMV) and white matter volumes (CWMV) in lobule X and a widespread cerebellar cortical thinning in patients. Overall disease severity and neurological disability, assessed with the Expanded Disability Status Severity Scale, was correlated with fatigue and information processing speed tasks, but not with CGMV and CWMV. CWMV and CGMV of lobule I-II was negatively correlated with information processing speed, as well as visuospatial memory tests and, finally, inverse cortical thinning associations were noted between the whole cerebellum, lobule I-II, lobule III, lobule VI, Crus I, lobule VIIIA and information processing speed and verbal fluency tasks. The inverse associations observed may represent a compensatory mechanism activated in MS engaging additional high-level cortical areas functionally interconnected with the damaged cerebellum, in order to cope with the cognitive demands of a task.

Differentiating between Good Readers and Poor Readers: The Role of Linguistic and Cognitive Factors

&#x0D; &#x0D; &#x0D; &#x0D; Attainment of reading ability is one of the most important goals of early elementary education. The goal of the present study was to compare groups of good readers and poor readers on several cognitive and linguistic skills and to determine the influence of these variables in differentiating these two groups of readers. An additional goal was to determine whether there are differences in proportion of boys and girls in groups of good and poor readers. The sample for this study comprised 60 third-grade children divided in two categories, 30 children in the category of good readers and 30 children in the category of poor readers. The results of this study revealed the largest differences between good readers and poor readers were on the phoneme deletion task and processing speed task. Another finding is that more boys than girls were in the group of good readers and more girls than boys in the group of poor readers. It is very important to know which underlying skills best differentiate good and poor readers at certain age. This in turn will lead to creating more effective reading interventions.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Psychosocial Stress Profiles and Cognitive Function in a Racially and Ethnically Diverse Sample of Adults

We developed comprehensive multi-domain profiles of psychosocial stress in urban-dwelling, racially and ethnically diverse adults (age range: 25-65; N=256; 63% Non-Hispanic Black; 25% Hispanic; 9% Non-Hispanic White) and evaluated associations with cognitive function. Participants completed psychosocial stress measures tapping into ten domains and tasks of processing speed, working memory, and episodic memory. Latent profile analyses controlling for age yielded four-profiles: high neighborhood stress, moderate versus high work stress and daily discrimination, and high health and relationship stress. Profiles significantly differed in income, age, and employment status. The profile with moderate work stress and daily discrimination and the profile with high neighborhood stress each had significantly lower working memory than the other profiles. The finding of lower working memory among individuals in the moderate work stress and daily discrimination profile was not due to sociodemographic variables. Results highlight the potentially cumulative influence of different contextual stressors on cognition.

Neuroanatomical Moderators of the Impact of Mild Behavioral Impairment on Cognition

Older adults with mild behavioral impairment (MBI), or the presence of late-life neuropsychiatric symptoms, have a unique cognitive phenotype. However, the neural correlates associated with MBI-related cognitive changes is not well understood. The goal of this study is to examine if specific regions of the brain moderate the relationship between the presence of MBI and performance on tasks of cognition. Data from the National Alzheimer’s Coordinating Center was utilized for this study. Participants (N=1,451) were included in our analyses if they were cognitively healthy or had mild cognitive impairment (MCI). Multiple domains of cognitive performance were evaluated. The neuroanatomical regions included hippocampus, caudal anterior cingulate (ACC), rostral ACC, entorhinal, and parahippocampal gray matter volume; and caudal ACC, rostral ACC, entorhinal, and parahippocampal mean cortical thickness. Hippocampal, entorhinal, and parahippocampal cortical gray matter volume moderated the relationship between MBI and performance on tasks of episodic memory. Left rostral ACC cortical gray matter volume and entorhinal and parahippocampal mean cortical thickness moderated the relationship between MBI and performance on language tasks. Hippocampi cortical gray matter volume also moderated the relationship between MBI and performance on processing speed tasks. Persons with smaller brain sizes in these areas were more negatively affected in these cognitive domains if they had MBI. These results suggest that the association between smaller brain volumes and cognition was stronger among persons with MBI. These findings suggest that older adults with MBI may perform worse on these tasks due to neurodegeneration that is present.

Impact of mild behavioral impairment on longitudinal changes in cognitive performance

AbstractBackgroundRecent research has developed a better appreciation for non‐cognitive factors, such as neuropsychiatric symptoms (NPS), as early indicators for dementia. This has led to the development of criteria for mild behavioral impairment (MBI), or the late‐life onset of NPS. MBI has been associated with a unique cognitive phenotype, but research on longitudinal changes is limited. The goal of this study is to examine if MBI influences changes in cognitive abilities among older adults who are cognitively healthy (CH) or have mild cognitive impairment (MCI).MethodSecondary data analysis of participants (n=17,291) from the National Alzheimer’s Coordinating Center who were CH (n=11,771) or diagnosed with MCI (n=5,520). Almost 25% of the sample met the operationalized diagnostic criteria for MBI (n=4,274). Cognitive performance was evaluated using tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed.ResultsCross‐sectionally, persons with MBI performed worse on tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed compared to people without MBI. There were no significant interactions present between MBI and MCI on any of the tasks. Longitudinally up to 14 years, persons with MBI saw a greater decline on tasks of attention, executive function, language, episodic memory, and processing speed compared to individuals without MBI. Further, older adults with MBI performed significantly worse across time on tasks of executive function, language, and processing speed when compared to CH older adults without MBI. Persons with MBI and MCI performed significantly worse across time on tasks of executive function, language, processing speed, and visuospatial ability when compared to those with only MCI.ConclusionOlder adults with MBI performed worse on all cognitive domains, compared to those without MBI. Additionally, CH older adults with MBI saw a greater decline across time in the domains of executive function, language, and processing speed. In the MCI group, MBI was associated with a greater decline in all of these domains in addition to visuospatial ability. The results provide support for unique cognitive phenotypes for MBI in CH older adults and MCI, that may be indicative of preclinical and prodromal symptoms of dementia.

Factors associated with subjective cognitive decline in older adults in pre‐clinical dementia phases

AbstractBackgroundThe phase of subjective cognitive decline (SCD) has shown inconsistency as a preclinical phase of dementia. Recent data show a greater association with emotional disturbances than cognitive aspects. Our objective was to analyze the factors associated with SCD in preclinical phases of dementia. Recent data show a greater association with emotional disturbances than cognitive aspects. Our objective was to analyze the factors associated with SCD in preclinical phases of dementia.MethodWe evaluated 94 older adults (Mean Age = , SD = ) with the MMSE, the Pfeiffer functional scale and the Yesavage geriatric depression scale. We also used a neuropsychological protocol that included memory, executive function, visuospatial, fluency and processing speed tasks. We applied a principal component analysis (PCA) to reduce dimensionality. Finally, we use logistic regression considering SCD as a dichotomous variable and sociodemographic and components extracted as a predictor.ResultWe observed that 48.35% of the older adults manifest subjective cognitive decline. Regression analysis shows that emotion (OR=1.839, IC95%: 1.268‐2.667) and older age (OR=1.282, IC95%: 1.068‐1.538) are associated with higher risk for SCD. Surprisingly, higher scores in memory factor are associated with an increased risk for SCD (OR=3.243, IC95%: 1.163‐9.038). On the other hand, lexical access factor Is associated with reduced risk of SCD (OR=0.389; IC95%: 0.159‐0.953).ConclusionThe SCD phase seems to be more associated with emotional states than cognitive performance, even older adults with better memory scores shows more complains about their cognitive performance. We suggest to follow‐up the sample and use validated instruments of SCD, neuroimaging data or fluid markers, to deep in the construct and validate its relevance as clinical marker.

Identifying and characterizing patterns of functional decline in memory clinic patients

AbstractBackgroundAlzheimer’s disease and related disorders (ADRD) are characterized by progressive cognitive and functional decline. To improve prognosis, it is important to predict the expected rate of functional decline. In the current study, we sought to uncover patterns of changes in everyday functioning among memory clinic patients, and to explore factors associated with said groups.MethodMemory clinic patients (N=573, 64.7±7.9 years old, 39% female) underwent extensive dementia screening at baseline, and were followed over time (median 1.0 years, range 0.3–6.2 years, N observations=1632). Diagnoses included subjective cognitive decline, mild cognitive impairment, and dementia with varying etiologies. We measured everyday functioning with the Amsterdam Instrumental Activities of Daily Living Questionnaire (A‐IADL‐Q). Longitudinal latent class analysis (LLCA) was used to identify groups of patients based on their rate of change in IADL, including non‐linear trajectories. We subsequently used random forests to explore the associations between the LLCA groups and demographics, neuropsychological test performance, and magnetic resonance imaging rating scales for medial temporal and global atrophy.ResultWe identified six groups: two stable (high and average), three declining (slow, moderate, and fast), and one improving group (see Table 1, Figure 1). All groups differed in baseline A‐IADL‐Q scores, with the declining groups having lower scores. The fast declining group consisted mostly of dementia patients, whereas the high stable group consisted mostly of patients with subjective cognitive decline. The area under the curve of the random forest classification was .95, thus accurately assigning patients to the correct group based on baseline characteristics. The following variables contributed most to the classification of the groups: baseline A‐IADL‐Q score (mean decrease accuracy [MDA]=200.5), a visuospatial task (copy of Rey Complex Figure, MDA=36.6) and a processing speed task (Letter Digit Substitution Task, MDA=18.5). Atrophy rating scales contributed less.ConclusionDifferent trajectories of functional decline were distinguished, and associated with baseline levels of cognitive and daily functioning. Our findings suggest that neuropsychological assessment may provide additional information on future changes in daily functioning. These findings may contribute to a more accurate prognosis of future functional decline, and by extension, future care needs.

Clinical features that differentiate young‐onset AD from young‐onset FTLD: An examination of the NACC UDS 3.0 and FTLD Module

AbstractBackgroundClinicopathologic studies reported that the NACC Uniform Dataset (UDS) 2.0 core measures do not adequately differentiate patients who ultimately died of Frontotemporal Lobar Degeneration (FTLD) from Alzheimer’s disease (AD). The FTLD Module (FTLD‐MOD) assesses core features of behavioral variant FTD (bvFTD) and primary progressive aphasia (PPA). Initial investigations suggest that the FTLD‐MOD improves discrimination between biomarker‐supported bvFTD and typical late‐onset AD, and that clinically diagnosed PPA participants performed worse than bvFTD on all FTLD‐MOD language tasks. However, the utility of these measures in the differential diagnosis of AD vs. major FTLD syndromes in young‐onset cases remains underexplored.MethodWe examined participants with age‐of‐onset &lt; 65 years in the ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) consortium and the Longitudinal Early Onset AD Study (LEADS). 115 bvFTD, 53 semantic variant PPA (svPPA), 29 non‐fluent variant PPA (nfvPPA) and 124 early‐onset AD (eoAD) cases completed the UDS3 and FLTD‐MOD. Linear regression analyses measured group differences in FLTD‐MOD raw scores and UDS3 neuropsychological z‐scores after accounting for group differences in demographic variables and global severity ratings. Alpha was 0.05 with Bonferroni corrections.ResultsParticipants with eoAD demonstrated the most impaired scores on tasks of attention, working memory, and processing speed, including Digit Span Backward (z=‐1.87) and Trails A (z=‐3.82). They also demonstrated difficulty on FTLD‐MOD language tasks with a working memory requirement (sentence repetition raw=3.68/5) and, as expected, memory (story delayed recall z=‐2.4z). svPPA performed the worst on FTLD‐MOD and UDS3 tasks assessing semantic memory, especially naming (all p’s ≤ 0.03). nfvPPA performed worst on sentence reading, sentence repetition, and letter fluency (all p’s ≤ 0.02). Consistent with previous work, these measures differentiate between bvFTD and PPA variants. However, relative to eoAD, bvFTD was equivalent (Trails B: bvFTDz=‐3.8, eoADz=‐3.82; p=0.12) or outperformed (sentence repetition: bvFTD=4.22/5, eoAD=3.68/5; p&lt;0.001) the eoAD group on all tasks.ConclusionsWe undertook this analysis to compare performance of the major young‐onset sporadic AD and FTLD clinical syndromes in the ALLFTD and LEADS studies. Results demonstrate relatively distinct cognitive profiles among eoAD, svPPA, and nfvPPA, but not in bvFTD. Future analyses will include FTLD‐MOD behavioral symptom questionnaires to assess their utility in differentiating bvFTD.

Disrupted functional connectivity in PD with probable RBD and its cognitive correlates

Recent studies associated rapid eye movement sleep behavior disorder (RBD) in Parkinson’s disease (PD) with severe cognitive impairment and brain atrophy. However, whole-brain functional connectivity has never been explored in this group of PD patients. In this study, whole-brain network-based statistics and graph-theoretical approaches were used to characterize resting-state interregional functional connectivity in PD with probable RBD (PD-pRBD) and its relationship with cognition. Our sample consisted of 30 healthy controls, 32 PD without probable RBD (PD-non pRBD), and 27 PD-pRBD. The PD-pRBD group showed reduced functional connectivity compared with controls mainly involving cingulate areas with temporal, frontal, insular, and thalamic regions (p < 0.001). Also, the PD-pRBD group showed reduced functional connectivity between right ventral posterior cingulate and left medial precuneus compared with PD-non pRBD (p < 0.05). We found increased normalized characteristic path length in PD-pRBD compared with PD-non pRBD. In the PD-pRBD group, mean connectivity strength from reduced connections correlated with visuoperceptual task and normalized characteristic path length correlated with processing speed and verbal memory tasks. This work demonstrates the existence of disrupted functional connectivity in PD-pRBD, together with abnormal network integrity, that supports its consideration as a severe PD subtype.

Sharper in the morning: Cognitive sundowning revealed with high‐frequency smartphone testing

AbstractBackgroundIn Alzheimer’s disease (AD), patients and caregivers often report a pattern of increasing cognitive and behavioral difficulties in evening hours, known colloquially as “sundowning.” Here, we describe the first known attempt to capture circadian fluctuations in cognition in humans at risk for AD using a novel smartphone assessment that samples cognition rapidly and repeatedly over a 7‐day period. We hypothesized that cognitive sundowning would manifest among individuals with abnormal AD biomarkers, even in preclinical stages of AD.MethodsOlder adults (N=168, Ages 61‐94 years) were asked to complete 4 brief smartphone‐based testing sessions per day for 7 consecutive days at quasi random intervals throughout the day, from morning until evening. Tests included associate memory, processing speed, and visual working memory tasks (Figure 1). Cerebrospinal fluid biomarkers for beta amyloid (Ab42) and phosphorylated tau181 (ptau) were collected within ∼3 years of smartphone tests. Scores from morning hours (range ∼5am – 12pm) were averaged for comparison with averaged scores from evening hours (after 12pm). Mixed effect models evaluated time of day effects by CSF biomarker status and clinical status.ResultsParticipant characteristics are provided in Table 1. Models with terms for age, gender, education, APOE e4 status, and Clinical Dementia Rating™ Sum of Boxes tested the interaction between time of day and CSF ptau/Ab42 ratio in predicting cognition (Figure 2). Compared to those with normal biomarkers, participants with abnormal CSF ptau/Aβ42 ratio had worse associate memory (p=0.03) and processing speed performance (p=0.026) in evening hours. On processing speed, participants with abnormal ptau/Aβ42 ratios were slower by an average of 700ms in the evening compared to those with normal ptau/Aβ42 ratios tested in morning hours. When models were run in cognitively normal participants only, a similar pattern was observed, confirming the hypothesis that increasing loads of AD pathology result in worse cognitive performance in evening hours prior to symptom onset.ConclusionOur results provide the first known evidence of cognitive sundowning in preclinical and early symptomatic AD and suggest that time of day is an important consideration for studies of cognition in AD populations.

Impact of Visual Discomfort Symptoms On SDMT Performance Among Persons With Multiple Sclerosis

<h3>Research Objectives</h3> To examine how visual discomfort symptoms affect performance on the symbol digit modalities test (SDMT), a visually mediated information processing speed task which is considered a gold standard measure for cognition in multiple sclerosis (MS) research. <h3>Design</h3> Observational, cross-sectional study. <h3>Setting</h3> General community. <h3>Participants</h3> Eighty-seven persons with MS and 30 healthy controls (HCs). <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Visual discomfort questionnaire (VDQ) and SDMT. <h3>Results</h3> Persons with MS reported significantly more severe visual discomfort symptoms on the VDQ than HCs (W = 424, p < 0.001). More severe visual discomfort symptoms was significantly associated with worse SDMT performance (ρ = -0.24, p = 0.011). Specifically, reports of symptoms such as text moving or fading while reading (p = 0.038), blurriness and diplopia (p = 0.055), having to re-read texts (p = 0.076), and slow reading (p = 0.008) were significantly related to SDMT performance, while symptoms related to headache and eye soreness (p = 0.824) and glare (p = 0.961) were not linked to SDMT performance. <h3>Conclusions</h3> Visual discomfort symptoms may impact/interfere with SDMT performance in persons with MS. When determining information processing speed deficits using the SDMT, visual discomfort symptoms need to be considered. <h3>Author(s) Disclosures</h3> Authors declare no conflicts of interest.

Who benefits from computerized cognitive training? Lower processing speed predicts greater cognitive improvement

• How does baseline cognition influence gains from computerized cognitive training? • Depressed young adults with lower processing speed show greater cognitive gains. • Gains were significantly greater in processing speed tasks. • Training type did not affect the relationship between baseline cognition and gains. Computerized cognitive training (CCT) is an intervention used to target cognitive deficits associated with depression, and has been found to improve mood, cognition, and everyday functioning. The aim of the present study is to determine if baseline cognitive presentation predicts improvement in cognition from CCT, and if this improvement varies based on the type of training received. Forty-six young adults with depressive symptoms were recruited as part of a randomized controlled trial studying the effects of CCT on mood, cognition, and everyday functioning. Participants completed training on their mobile devices for 15 min/day, 5 days/week, for 8 weeks. Clinical and neuropsychological assessments were completed at baseline and 8 weeks. Individuals with below average processing speed (PS) scores showed greater improvement in 2 out of 4 PS tasks (Cohen's d range > 1) compared to above average performers. The high and low performers did not differ in change in performance in non-PS tasks. Type of training had no effect. Small college-aged sample. CCT has differential effects on PS depending on baseline cognitive presentation. Individuals with an initial relative PS weakness improve more from CCT than those with higher baseline functioning. This study highlights the importance of identifying individual differences in cognition that may factor into CCT response.