Cognitive Subtypes Research Articles

Behavioral variations among vascular cognitive impairment subtypes – A comparative study

Dementia of vascular origin is a distinct variety with a heterogeneous neuropsychological profile. Very few studies have compared the behavioral dysfunction in the large vessel and small vessel vascular dementia (VaD) and studied the association between executive dysfunction and behavioral dysfunction documented in these patients, between the white matter load in small vessel disease (SVD) and the behavioral dysfunction. 76 patients having a modified Hachinski Ischemic Scale score of ≥ 4 were recruited and categorized into a small vessel and large vessel VaD. The Neuropsychiatric Inventory (NPI) score ≥ 4 per domain for defining clinically relevant symptoms and the Clinical Dementia Rating Scale (CDR) for evaluating the severity of dementia were used. Behavioral and Psychological Symptoms of Dementia (BPSD) were present in 66.67% of patients with SVD and 53.57% of those having large vessel disease. Apathy, euphoria, and disinhibition were more common in SVD, while appetite alterations were more common in large vessel disease. Behavioral dysfunction was also associated with executive dysfunction in both the VaD subtypes and with white matter loads in SVD. We conclude that different VaD subtypes have different behavioral profiles. This might help in understanding the underlying pathophysiology, diagnosis and thus better management of this disorder.

The Interaction of Cognitive Profiles and Text-to-Speech Software on Reading Comprehension of Adolescents With Reading Challenges

This study utilized the Simple View of Reading (SVR) model cognitive subtypes to determine the impact of text-to-speech (TTS) software on the reading comprehension of 94 grade 8 students with reading difficulties. Method: paired samples t tests for all four SVR groups were conducted to examine reading comprehension scores under TTS and no-TTS conditions. Results: only those participants with a dyslexic profile (listening comprehension greater than decoding skills), demonstrated significant gains in reading comprehension in the TTS compared to the no-TTS condition; a large effect size (1.58 grade level increase) was found. Furthermore, this group’s literal comprehension improved much more than their inferential comprehension when utilizing TTS. Implications: a one-size fits all approach for the selection of TTS for struggling readers is not recommended. SVR subtyping incorporated into psychoeducational assessments can inform appropriate assignment of TTS to struggling readers.

P 39. Evaluation of cognitive subtypes in Parkinson's disease – Correlations with qEEG power spectra

Introduction. According to the Dual Syndrome Hypothesis cognitive impairment in Parkinson's disease (PD) patients can be divided into two subtypes: The frontal type versus the posterior type. The risk of progression to PD dementia was described to be higher in patients initially presenting with posterior deficits. Additionally, cognitive impairment in PD is related to slowing of EEG background activity. The aim of the present study was to investigate the correlation between different cognitive subtypes and qEEG measures in PD-patients. Methods. Fifty-nine PD-patients completed a comprehensive neuropsychological test battery covering five cognitive domains (Executive Function, Episodic Memory, Attention, Visuo-Spatial Ability, Language). Additionally, a 256-resting-state EEG was recorded. For statistics, Principal Component Analysis was calculated to group the neuropsychological measures into independent factors. Factor scores were further correlated with qEEG power spectra through Pearson“s correlation. Results. From screeplot two factors were derived. Factor 1 consisted of tests measuring constructional praxis, visuo-episodic memory as well as Stroop interference. Factor 2 consisted of tests assessing executive functions, attention, verbal-episodic memory and language. Pearson's correlation with qEEG measures and Factor 2 showed significant positive correlations with Global Alpha_2 Power (10–13 Hz; r = 0.35, p < 0.01) and Global Beta Power (13–30 Hz; r = 0.28; p < 0.05). There was a negative correlation between Factor 2 and Global Theta Power (4–8 Hz; r = −0.31, p < 0.05). No correlation with Factor 1 was found. Conclusion. From Principal Component analysis two factors were derived of our comprehensive neuropsychological test battery. In our sample, fronto-temporal associated neuropsychological measures were meaningfully correlated with qEEG power spectra. In a further step, correlation with connectivity measures of the qEEG power spectra could allow a closer insight into underlying network dynamics.

Absolute Cardiovascular Disease Risk Is Associated With the Incidence of Non-amnestic Cognitive Impairment in Japanese Older Adults.

BackgroundThe estimated absolute cardiovascular disease (CVD) risk level is known to be a useful surrogate marker for future cognitive impairment; however, evidence regarding its predictive validity in terms of cognitive subtypes is limited. We aimed to examine subtype-dependent differences in the associations between absolute CVD risk and the incidence of cognitive impairment in a community-dwelling older Japanese cohort.Methods and ResultsThis study comprised 1,641 cognitively intact older Japanese participants without CVDs at baseline. We estimated absolute CVD risk using WHO region-specific risk estimation charts and included age, sex, diabetes mellitus, smoking, systolic blood pressure, and total cholesterol at baseline, and the CVD risk level was stratified into the three following risk categories: low (<10%), moderate (10 to <20%), and high (≥20%). Objective cognitive screening was performed using a multicomponent neurocognitive test at baseline and follow-up, and the incidence of cognitive impairment over 48 ± 2 months was determined. The incidence of cognitive impairment in low-, moderate-, and high-CVD risk participants was 1.2, 3.0, and 5.4%, respectively, for amnestic subtypes and 5.8, 10.1, and 14.0%, respectively, for non-amnestic subtypes. After adjusting for potential confounding factors, the absolute CVD risk level was significantly associated with non-amnestic impairment but not with amnestic impairment.ConclusionsThe absolute CVD risk estimated using region-specific risk estimation charts in old age is useful to predict incidence of cognitive impairment. Strategies to screen populations at risk of cognitive impairment and to prevent progression to dementia should be cognitive subtype-specific.

Children With Chinese Dyslexia Acquiring English Literacy: Interaction Between Cognitive Subtypes of Dyslexia and Orthographies

This study investigated the impact of Chinese dyslexia subtypes on English literacy skills (i.e., reading fluency and dictation) in Hong Kong children. Eighty-four Cantonese-speaking children officially diagnosed with dyslexia (Mage = 103 months) and 48 age-matched typically developing (TD) children were tested. Cluster analysis with performances on Chinese syllable awareness (CSA), Chinese phonemic awareness (CPA), Chinese phonological memory (CPM), Chinese orthographic awareness (COA), and matrix reasoning (MR) yielded three cognitive subtypes: the phonological deficit (PD) subtype, the orthographic deficit (OD) subtype, and the global deficit (GD) subtype. After controlling for English language experience, age, and gender, all three dyslexia subtype groups performed significantly worse in English word reading fluency and dictation than the TD children. In addition, the PD group performed worse in English PA; the OD group performed worse in English OA; and the GD group performed worse in all English skills except English PM. We compared the level of impairment in literacy between languages and dyslexia subtypes. In word reading fluency, all subtype groups experienced less impairment in English than Chinese, while the OD group showed the largest English advantage. In dictation, only the OD group showed a significant language effect favoring English. The findings suggest that different subtypes of Chinese dyslexia bear different risks for difficulties in English literacy.

Robust Discovery of Mild Cognitive Impairment Subtypes and Their Risk of Alzheimer's Disease Conversion Using Unsupervised Machine Learning and Gaussian Mixture Modeling.

Alzheimer's Disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills. The ability to correctly predict the diagnosis of Alzheimer's disease in its earliest stages can help physicians make more informed clinical decisions on therapy plans. This study aimed to determine whether the unsupervised discovering of latent classes of subjects with Mild Cognitive Impairment (MCI) may be useful in finding different prodromal AD stages and/or subjects with a low MCI to AD conversion risk. Total 18 features relevant to the MCI to AD conversion process led to the identification of 681 subjects with early MCI. Subjects were divided into training (70%) and validation (30%) sets. Subjects from the training set were analyzed using consensus clustering, and Gaussian Mixture Models (GMM) were used to describe the latent classes. The discovered GMM predicted the latent class of the validation set. Finally, descriptive statistics, rates of conversion, and Odds Ratios (OR) were computed for each discovered class. Through consensus clustering, we discovered three different clusters among MCI subjects. The three clusters were associated with low-risk (OR = 0.12, 95%CI = 0.04 to 0.3|), medium-risk (OR = 1.33, 95%CI = 0.75 to 2.37), and high-risk (OR = 3.02, 95%CI = 1.64 to 5.57) of converting from MCI to AD, with the high-risk and low-risk groups highly contrasting. Hence, prodromal AD subjects were present in only two clusters. We successfully discovered three different latent classes among MCI subjects with varied risks of MCI-to-AD conversion through consensus clustering. Two of the discovered classes may represent two different prodromal presentations of Alzheimer´s disease.

Clinical and Objective Cognitive Measures for the Diagnosis of Cognitive Frailty Subtypes: A Comparative Study.

BackgroundCognitive frailty (CF) includes reversible and potentially reversible subtypes; the former is known as concurrent physical frailty (PF) and pre-mild cognitive impairment subjective cognitive decline (pre-MCI SCD), whereas the latter is known as concurrent PF and MCI. The diagnoses of pre-MCI SCD and MCI are based on clinical criteria and various subjective cognitive decline questionnaires. Heterogeneous assessment of cognitive impairment (CI) results in significant variability of CI, CF, and their subtype prevalence in various population-based studies.ObjectiveThis study aimed to compare the classification differences in CI and CF subtypes from PF and normal cognition by applying clinical and objective cognitive criteria. Clinical criteria comprised Fried PF and clinical MCI criteria combined with the SCD questionnaire, whereas objective criteria comprised Fried PF and objective cognitive criteria based on the norm-adjusted six neuropsychological test scores.MethodsOf the 335 volunteers (age ≥ 60 years) in this study, 191 were diagnosed with CI based on clinical cognitive diagnosis criteria, and 144 were identified as robust normal based on objective cognitive assessment from the community-dwelling older adult cohort. Individuals with clinical CI, including 94 with MCI and 97 with pre-MCI SCD, were reclassified into different z-score-derived MCI, pre-MCI SCD, and normal subgroups based on objective cognitive criteria. The classification diagnostic accuracy of normal cognition, PF, pre-MCI, MCI, CF, and CF subtypes based on clinical and objective criteria was compared before and after adjusting for age, sex, and education level.ResultsThe reclassification of objective assessments indicated better performance than that of clinical assessments in terms of discerning CI severity among different subgroups before adjusting for demographic factors. After covariate adjustment, clinical assessments significantly improved the ability to cognitively discriminate normal individuals from those with pre-MCI SCD and MCI but not the z-score-derived pre-MCI SCD and MCI groups from the robust normal group. Furthermore, the adjustment did not improve the ability to discriminate among individuals with reversible CF from those with potentially reversible CF and pre-MCI only SCD from MCI only SCD.ConclusionsObjective criteria showed better performance than clinical criteria in the diagnosis of individuals with CI or CF subtypes. Rapid clinical cognitive screening in combination with normative z-scores criteria is cost effective and sustainable in clinical practice.

Defining Heterogeneous Cognitive Trajectories in Bipolar Disorder: A Perspective.

Bipolar disorder (BD) is a highly disabling mental illness that affects approximately 1% of the global population. Cognitive capacity is a strong predictor of "everyday" functional outcome in BD and should thus be considered a key treatment target. Interventions to improve cognition have been largely unsuccessful, likely due to the substantial heterogeneity inherent to the illness. It is known that 40%-60% of people with BD have cognitive impairment, yet impairment is not "one size fits all"; in fact, the literature supports discrete cognitive subtypes in BD (e.g., intact, globally impaired, and selectively impaired). Gaining a better understanding of these cognitive subtypes, their longitudinal trajectories, and their biological underpinnings will be essential for improving patient outcomes. The prevailing hypothesis for the development of cognitive impairment in BD postulates a stepwise cumulative effect of repeated mood episodes causing wear-and-tear on the brain. However, a paucity of data supports this idea at the group level. We propose that studying heterogeneity longitudinally will allow for clearer delineation of the natural history of cognitive trajectories in BD. In sum, parsing heterogeneity in BD will allow us to identify causal mechanisms and optimize treatment at the level of the individual.

Diet-Cognition Associations Differ in Mild Cognitive Impairment Subtypes.

Cognitive function is not generally associated with diet, and there is debate over that association. Moreover, little is known about such associations with the specific cognitive domains and subtypes of mild cognitive impairment (MCI). We analyzed data of 4309 Chinese adults aged 55 and over from the Community-based Cohort Study on Nervous System Diseases from 2018–2019. Dietary habits were assessed at inclusion using a validated semi-quantitative food frequency questionnaire. Cognitive function of the participants was measured by using the Montreal Cognitive Assessment. Analyses were performed using multiple logistic regression and quantile regression with adjustment for socio-demographic, lifestyle, and health-related factors. Compared with normal cognition participants, those with a worse cognition state were characterized as being an older age and lower economic level. After adjustment for potential factors, participants with higher consumption of rice, legumes, fresh vegetables, fresh fruit, pork, poultry, fish, and nuts tended to have higher scores of global cognitive function and domains, and to have lower odds of MCI, while those with higher consumption levels of wheat and eggs had worse cognition, compared with the corresponding bottom consumption level of each food. Participants with a medium consumption level of beef or mutton had 57% (OR: 1.57, 95%CI: 1.07–2.32) higher odds of aMCI-SD, whereas they had 50% (OR: 0.50, 95%CI: 0.34–0.73) lower odds of naMCI-MD. Similarly, the highest consumption level of dairy was positively associated with the odds of aMCI-SD (OR:1.51, 95%CI:1.00–2.29), but inversely linked to the odds of naMCI-SD (OR: 0.60, 95%CI: 0.38–0.93) and naMCI-MD (OR: 0.49, 95%CI: 0.29–0.82). Most diet global cognitive benefits were observed to be associated with the preexisting higher consumption of rice, legumes, fresh vegetables, fresh fruit, meat, and nuts. In addition, the heterogeneity of associations between the consumption of certain foods and MCI subtypes was observed among Chinese adults aged over 55 years. These cross-sectional observations require validation in prospective studies.

Is executive dysfunction a potential contributor to the comorbidity between basic reading disability and attention-deficit/hyperactivity disorder?

ABSTRACT Our study is one of the few to analyze executive functioning (EF) in a comprehensive, multi-modal fashion as a potential contributor to the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and basic reading disability (RD). We included multiple, traditional, neuropsychological measures of EF, along with the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire, to assess inhibit, shift, working memory (WM), planning, generation fluency, and problem-solving. Participants included 263 children, ages 8–12 years, with RD, ADHD, RD/ADHD, and typically developing controls. When using the traditional measures in a 2 × 2 MANCOVA, we found both RD and ADHD had poor cognitive EF in most areas at the group level, with phonological loop deficits being more specific to RD and behavioral regulation deficits being more specific to ADHD. Children with RD/ADHD performed comparably to those with RD and ADHD alone. Results were similar on the BRIEF. In contrast, only WM predicted both basic reading and inattention when the data were assessed in a continuous fashion. It also explained the correlations between basic reading and inattention, being worthy of longitudinal research to determine if it is a shared contributor to RD/ADHD. When comparing hypotheses as to the nature of RD/ADHD, we found the multiple deficit hypothesis was better supported by our EF data than the phenocopy hypothesis or the cognitive subtype hypothesis.

Apathy is associated with parietal cortical-subcortical dysfunction in ALS

Apathy is the core behavioural feature of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS). Initiation and emotional manifestations of apathy significantly affect patients and carers, particularly in terms of quality of life. As such, the primary aim of the present study was to investigate the prevalence and neural correlates of initiation, and emotional subtypes of apathy in ALS. A total of 109 participants were recruited from a specialised, tertiary referral ALS/FTD clinic. Overall rates of apathy, including cognitive, initiation and emotion subtypes as assessed by the Dimensional Apathy Scale (DAS), were examined and correlated with brain volumes, including voxel-based morphometry on high resolution MRI. Clinically significant apathy ranged between 49% (patient-rated DAS) and 64% (carer-rated DAS), with the most common apathy subtypes being initiation (84–96%) and emotional (74–75%) apathy. The results of the two-way repeated measures ANOVA revealed significant differences across the DAS executive, emotional and initiation subscales (p = .0001). Multivariate analysis using a logistic regression model showed that only initiation; (odds ratio = 3.08, p = .004) and emotional (odds ratio = 2.40, p = .008) apathy were predictive of clinically significant apathy, controlling for education and depression. Increased initiation apathy correlated with reduced grey matter within bilateral superior frontal gyrus and increased emotional apathy correlated with reduced grey matter in prefrontal cortices and right anterior cingulate, previously implicated in apathy. Additional correlations were identified including the angular gyrus (or the temporo-parietal junction), important in reward valuation and subsequent goal-directed behaviour. Taken together, results from the present series highlight the frequency and multi-dimensionality of apathy in ALS. The pathophysiological mechanisms of apathy in ALS may be critically underpinned by neurodegeneration across a distributed brain network, with key roles in task initiation, emotion, reward processing and subsequent goal-directed behaviour.

Frailty and Risk of Dementia in Mild Cognitive Impairment Subtypes.

Risk factors for developing dementia from mild cognitive impairment (MCI) probably differ between MCI subtypes. We investigated how frailty relates to dementia risk in amnestic MCI (a-MCI; n=2,799) and non-amnestic MCI (na-MCI; n=629) in the National Alzheimer's Coordinating Center database. Although higher frailty increased dementia risk for people with either a-MCI or na-MCI, the larger risk was in na-MCI (interaction hazard ratio=1.35 [95% confidence interval=1.15-1.59], p < 0.001). Even after the onset of clinically significant cognitive impairment, poor general health, quantified by a high degree of frailty, is a significant risk for dementia. ANN NEUROL 2021;89:1221-1225.

Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

Prevalence of mild cognitive impairment in surgical menopause: subtypes and associated factors

Objective The aim of this study was to determine the prevalence and associated factors of mild cognitive impairment (MCI) and subtypes, amnestic MCI (aMCI) and non-amnestic MCI (naMCI), in women with surgical menopause. Methods We obtained the database containing information for 200 women with surgical menopause from our previous study. The Montreal Cognitive Assessment – total score, the Montreal Cognitive Assessment – memory index score (MoCA-MIS) and their age, years since menopause, education, medical and surgical history, hormone therapy use, exercise, sleep duration, alcohol use, smoking and family history of dementia were obtained. All participants without the MoCA-MIS were excluded. Result The average age of the 164 participants was 56.3 ± 6.9 years. The prevalence of MCI, aMCI and naMCI was 43.3%, 9.8% and 33.5%, respectively. The duration of education reduced MCI for 93% (95% confidence interval 0.03–0.20) of the women. In late postmenopause, hormone therapy >10 years showed 47% lower prevalence of MCI (age-adjusted odds ratio = 0.53, 95% confidence interval 0.22–1.28). Finally, length of education was the only independent factor associated with MCI and its subtypes. Conclusion We found a high prevalence of MCI and the non-amnestic subtype in women with surgical menopause. Further study is needed to clarify the long-term effects of surgical menopause on cognitive function.

Cognitive subtypes in individuals with essential tremor seeking deep brain stimulation

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET (N = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches (K-means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group (N = 64), Low Memory Multi-Domain group (N = 41), and Cognitively Normal group (N = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Empfehlungen zur neuropsychologischen Diagnostik beim Morbus Parkinson

Presence of mild cognitive impairment is currently the best predictor for the development of Parkinson's disease dementia. Diagnostic criteria for both Parkinson's with mild cognitive impairment and Parkinson's disease dementia have been suggested by the Movement Disorder Society. However, not all cognitive tests recommended are available in the German language with proper standard values. To define evidence-based guidelines for neuropsychological assessment of patients with Parkinson's disease in German. Two systematic literature searches were conducted. First, articles that presented international guidelines (consensus papers or reviews) for the application of standardized neuropsychological assessments for the diagnosis of cognitive impairment in Parkinson's disease were selected. Of those, only neuropsychological assessments in German language with normative values referring either to a German, Austrian, or Swiss population were considered. Second, articles comparing test performances of healthy controls vs. Parkinson's disease and/or different cognitive Parkinson's disease subtypes (e.g. no cognitive impairment, Parkinson's with mild cognitive impairment, Parkinson's disease dementia) were selected. Effect sizes for group differentiation were calculated. Out of 127 full-text articles reviewed, 48 tests were identified during the first literature search. In the second search, 1716 articles were reviewed and 23 papers selected. The strongest effect sizes for group discrimination were revealed for tests assessing executive function, attention, and visuo-cognitive abilities. Based on the results of the two literature searches, consensus guidelines were defined by the authors, allowing for Level-II diagnosis for Parkinson's with mild cognitive impairment and Parkinson's disease dementia. The presented guidelines may have the potential to standardize and improve the neuropsychological assessment of Parkinson's disease patients in German speaking countries.

Aberrant triple-network connectivity patterns discriminate biotypes of first-episode medication-naive schizophrenia in two large independent cohorts.

Schizophrenia is a complex disorder associated with aberrant brain functional connectivity. This study aims to demonstrate the relation of heterogeneous symptomatology in this disorder to distinct brain connectivity patterns within the triple-network model. The study sample comprised 300 first-episode antipsychotic-naive patients with schizophrenia (FES) and 301 healthy controls (HCs). At baseline, resting-state functional magnetic resonance imaging data were captured for each participant, and concomitant neurocognitive functions were evaluated outside the scanner. Clinical information of 49 FES in the discovery dataset were reevaluated at a 6-week follow-up. Differential features between FES and HCs were selected from triple-network connectivity profiles. Cutting-edge unsupervised machine learning algorithms were used to define patient subtypes. Clinical and cognitive variables were compared between patient subgroups. Two FES subgroups with differing triple-network connectivity profiles were identified in the discovery dataset and confirmed in an independent hold-out cohort. One patient subgroup appearing to have more severe clinical symptoms was distinguished by salience network (SN)-centered hypoconnectivity, which was associated with greater impairments in sustained attention. The other subgroup exhibited hyperconnectivity and manifested greater deficits in cognitive flexibility. The SN-centered hypoconnectivity subgroup had more persistent negative symptoms at the 6-week follow-up than the hyperconnectivity subgroup. The present study illustrates that clinically relevant cognitive subtypes of schizophrenia may be associated with distinct differences in connectivity in the triple-network model. This categorization may foster further analysis of the effects of therapy on these network connectivity patterns, which may help to guide therapeutic choices to effectively reach personalized treatment goals.

Gait analysis as a clinical tool for dementia: current perspectives and future challenges

Gait, the way that we walk, requires complex cognitive functions. Gait may be a useful early marker for dementia diagnosis, as gait impairments precede and reflect cognitive decline. Early diagnosis of dementia enables individuals and their families to make informed decisions about their care plans, and allows researchers to understand preclinical and prodromal disease stages, providing novel targets for drug therapies. As such, a range of biomarkers are being developed to improve early and accurate diagnosis, including gait analysis. This editorial will outline how gait analysis can support the clinical diagnosis of dementia, including evidence of unique signatures of gait which can aid the identification of cognitive impairment and discrete dementia disease subtypes, the potential use of wearable technology to assess gait in the clinic and the real world, and key recommendations for the future implementation of gait into the diagnostic toolkit for dementia.

Causal associations of intelligence with schizophrenia and bipolar disorder: A Mendelian randomization analysis.

Intelligence is inversely associated with schizophrenia (SCZ) and bipolar disorder (BD); it remains unclear whether low intelligence is a cause or consequence. We investigated causal associations of intelligence with SCZ or BD risk and a shared risk between SCZ and BD and SCZ-specific risk. To estimate putative causal associations, we performed multi-single nucleotide polymorphism (SNP) Mendelian randomization (MR) using generalized summary-data-based MR (GSMR). Summary-level datasets from five GWASs (intelligence, SCZ vs. control [CON], BD vs. CON, SCZ+BD vs. CON, and SCZ vs. BD; sample sizes of up to 269,867) were utilized. A strong bidirectional association between risks for SCZ and BD was observed (odds ratio; ORSCZ→BD=1.47, p=2.89×10-41, ORBD→SCZ=1.44, p=1.85×10-52). Low intelligence was bidirectionally associated with a high risk for SCZ, with a stronger effect of intelligence on SCZ risk (ORlower intelligence → SCZ=1.62, p=3.23×10-14) than the reverse (ORSCZ→lower intelligence=1.06, p=3.70×10-23). Furthermore, low intelligence affected a shared risk between SCZ and BD (OR lower intelligence → SCZ+BD=1.23, p=3.41×10-5) and SCZ-specific risk (ORlower intelligence → SCZvsBD=1.64, p=9.72×10-10); the shared risk (ORSCZ+BD→lower intelligence=1.04, p=3.09×10-14) but not SCZ-specific risk (ORSCZvsBD→lower intelligence=1.00, p=0.88) weakly affected low intelligence. Conversely, there was no significant causal association between intelligence and BD risk (p>0.05). These findings support observational studies showing that patients with SCZ display impairment in premorbid intelligence and intelligence decline. Moreover, a shared factor between SCZ and BD might contribute to impairment in premorbid intelligence and intelligence decline but SCZ-specific factors might be affected by impairment in premorbid intelligence. We suggest that patients with these genetic factors should be categorized as having a cognitive disorder SCZ or BD subtype.

Metabolic correlates of neuropsychological assessment in behavioral variant frontotemporal dementia

AbstractBackgroundNeuropsychological assessment is an essential tool in the diagnosis and monitoring of patients with neurodegenerative disorders. Cognitive functions underlying neuropsychological tests are complex, and accordingly interpretation is often challenging. In behavioral variant frontotemporal dementia (bvFTD), neural correlates of cognitive testing are largely unknown, and they could be different to other settings such as Alzheimer’s disease (AD). In this study, we aimed to analyze the metabolic underpinnings of neuropsychological test results in a series of patients with bvFTD.MethodSeventy‐two patients with bv‐FTD according to the consensus criteria were included. Patients were examined with a comprehensive neuropsychological protocol and 18F‐FDG‐PET. Voxel‐based analysis was used to study the correlation between regional brain metabolism and cognitive performance of the following tests: Boston Naming Test (BNT), Trail Making Test (TMT), Rey‐Osterrieth Complex Figure, verbal fluency (semantic and phonological), Free and Cued Selective Reminding Test (FCSRT), Stroop Color Word Interference test, Tower of London, and Visual Object and Space Perception Battery (VOSP). Age, sex, and years of education were introduced as nuisance covariates. A healthy control and Alzheimer’s disease groups were also examined with the same protocol for comparison. Neuroimaging analyses were conducted using SPM12.ResultMean age in the bvFTD group was 71.33+/‐7.75 years, and 43 (59.7%) were men. In bvFTD, BNT was positively correlated with the left anterior temporal lobe; FCSRT was correlated with the left frontal cortex; Phonological fluency with left frontal lobe and right superior frontal; semantic fluency with left frontal, temporal and thalamus; TMT‐B was negatively correlated with bilateral medial frontal lobes, especially with the right side; VOSP was correlated with the right frontal lobe.ConclusionWe showed the brain regions associated to the performance of different standardized neuropsychological tests in bvFTD. The differences observed between bvFTD and AD suggests that neural underpinnings underlying these tests are different according to each disease, confirming the multiple cognitive processes involved during performance of each particular test. Overall, our study provides useful information to achieve a better understanding of neuropsychological examination in patients with bvFTD. In addition, these findings could be useful to detect cognitive subtypes within the syndrome of bvFTD.