Cognitive Subtypes Research Articles

Global assessment, cognitive profile, and characteristics of mild cognitive impairment in Parkinson's disease.

Cognitive deficits are evident throughout the course of Parkinson's disease (PD), with 24% of patients experiencing subtle cognitive disturbances at the time of diagnosis, and with up to 80% of patients developing PD dementia (PDD) at advanced stages of the disease PD patients with mild cognitive impairment (MCI), an at-risk phenotype of PDD, present with heterogeneous clinical characteristics that complicate the management of PD. This study aims to examine the characteristics of PD-MCI by using the Movement Disorder Society (MDS) diagnostic criteria and evaluate the validity of global cognitive scales in identifying PD-MCI. Seventy-nine (79) PD patients completed neuropsychological assessments and a comprehensive cognitive battery. PD-MCI was classified according to the level 2 MDS task force criteria. Mini-Mental State Examination (sMMSE), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Cognitive Rating Scale (PDCRS) were examined against a level 2 dichotomised PD-MCI diagnosis. Characteristics of PD-MCI were evaluated using logistic regression analysis. Twenty-seven patients met criteria for PD-MCI (34%). The MoCA and PDCRS demonstrated high validity to screen for PD-MCI. Impairments in multiple cognitive domains were observed in 77.8% of PD-MCI patients. There were significantly more males in the PD-MCI group compared to PD patients without MCI (p<0.01). PD patients with MCI exhibited impairments in the attention/working memory, executive function and memory domains. Heterogeneous cognitive characteristics in PD warrant further investigation into specific cognitive subtypes to advance understanding and effective evaluation of PD-MCI.

Cognitive subtyping of university students with dyslexia in a semi-transparent orthography: what can weaknesses and strengths tell us about compensation?

Developmental dyslexia is characterized by a profile of reading- and writing-related difficulties which stands out as a core deficit in phonological processing. Although these difficulties seem to persist into adulthood, it is still an open question to what extent they are immune, or not, to the extensive training resulting from extended schooling. The main objective of this study was to explore the heterogeneity of the cognitive profile of European Portuguese highly literate adults with dyslexia. Thirty-one university students diagnosed with dyslexia during childhood and their matched skilled adult control readers were assessed through a battery of reading and cognitive tests. A cluster analysis of data obtained from participants with dyslexia identified two profile groups. While Cluster 1 grouped participants with clear phonological deficits and concomitant reading difficulties, Cluster 2 showed better performance on most of the core skills associated with reading and also better general cognitive abilities, suggesting that these dyslexic readers have partially resolved their phonological constraints along the development, probably due to the systematic exposure to reading and writing. As Cluster 2 matched typical readers in general cognitive abilities, it might also be the case that cognitive strengths associated with general intelligence worked as protective factors, helping students to strategically compensate for their reading difficulties. Overall, these results suggest that both mechanisms–partial remediation of the core phonological deficit and adoption of compensatory strategies supported by general cognitive skills–might contribute together to improving the reading performance of highly literate adults with dyslexia.

Social cognition and apathy between two cognitive subtypes of schizophrenia: Are there the same or different profiles?

ObjectiveCognitive impairment is an essential feature of schizophrenia, and it involves a broad array of nonsocial and social cognitive domains. This study aimed to examine whether there are the same or different social cognition profiles between two cognitive subtypes of schizophrenia. MethodThere were one hundred and two chronic and institutionalized patients with schizophrenia from two referral tracks. One group is “Cognitively Normal Range” (CNR) (N = 52), and another group is “Below Normal Range” (BNR) (N = 50). We assessed or collected their apathy, emotional perception judgment, facial expression judgment, and empathy by the Apathy Evaluation Scale, the International Affective Picture System, the Japanese and Caucasian Facial Expression of Emotion, and the Interpersonal Reactivity Index, respectively. ResultsWe found different impairment profiles depending on the cognitive subtypes of the patient with schizophrenia. Surprisingly, the CNR presented impairments in apathy, emotional perception judgment, facial expression judgment, and empathy and feature impairment in empathy and affective apathy. In contrast, even though the BNR had significant neurocognition impairments, they had almost intact empathy with significantly impaired cognitive apathy. Both groups' global deficit scores (GDSs) were comparable, and all reached at least a mild impairment level. ConclusionsThe CNR and the BNR had similar abilities in emotional perception judgment and facial emotion recognition. They also had differentiable deficits in apathy and empathy. Our findings provide important clinical implications for neuropsychological pathology and treatment in schizophrenia.

Biopsychosocial frailty and mild cognitive impairment subtypes: Findings from the Italian project on the epidemiology of Alzheimer's disease (IPREA).

Frailty is a critical intermediate status of the aging process including physical, cognitive, and psychosocial phenotypes. We operationalized a biopsychosocial frailty construct, estimating its association with mild cognitive impairment (MCI) and its subtypes. In 1980, older individuals from the population-based Italian PRoject on the Epidemiology of Alzheimer's disease (IPREA), we investigated cross-sectional associations among biopsychosocial frailty, MCI, and its subtypes. Participants with biopsychosocial frailty showed an increased odds ratio (OR) of MCI [OR: 4.36; 95% confidence interval (CI): 2.60-7.29; Fisher's exact p<0.01], particularly for nonamnestic MCI single domain (naMCI-SD, OR:3.28; 95% CI: 1.35-7.97; Fisher's exact p=0.02) and for nonamnestic MCI multiple domain (naMCI-MD, OR:6.92; 95% CI: 3.37-14.21; Fisher's exact p<0.01). No statistically significant associations between amnestic MCI single or multiple domain and biopsychosocial frailty were observed. In a large, older Italian cohort, a biopsychosocial frailty phenotype was associated with MCI, in particular, could be associated with some of its subtypes, that is, naMCI-SD, and naMCI-MD.

A graph theoretic approach to neurodegeneration: five data-driven neuropsychological subtypes in mild cognitive impairment

ABSTRACT Mild cognitive Impairment (MCI) is notoriously heterogenous in terms of clinical presentation, neuroimaging correlates, and subsequent progression. Predicting who will progress to dementia, which type of dementia, and over what timeframe is challenging. Previous work has attempted to identify MCI subtypes using neuropsychological measures in an effort to address this challenge; however, there is no consensus on approach, which may account for some of the variability. Using a hierarchical community detection approach, we examined cognitive subtypes within an MCI sample (from the Alzheimer’s Disease Neuroimaging Initiative [ADNI] study). We then examined whether these subtypes were related to biomarkers (e.g., cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. We identified five communities (i.e., cognitive subtypes) within the MCI sample: 1) predominantly memory impairment, 2) predominantly language impairment, 3) cognitively normal, 4) multidomain, with notable executive dysfunction, 5) multidomain, with notable processing speed impairment. Community membership was significantly associated with 1) cortical volume in the hippocampus, entorhinal cortex, and fusiform cortex; 2) FDG PET hypometabolism in the posterior cingulate, angular gyrus, and inferior/middle temporal gyrus; and 3) conversion to dementia at follow up. Overall, community detection as an approach appears a viable method for identifying unique cognitive subtypes in a neurodegenerative sample that were linked to several meaningful biomarkers and modestly with progression at one year follow up.

Detection of Cognitive Subtypes of Schizophrenia (with Assessment of Perceptual Disorders). A Pilot Study

Background: the heterogeneity of schizophrenia impedes our efforts to provide adequate treatment. One step toward optimizing treatment is to deepen our understanding of cognitive variety in this disorder. Perhaps due to this heterogeneity, although visual impairment is a frequent symptom of schizophrenia, many studies show inconsistent data. The aim of our study was to identify homogeneous groups of patients with schizophrenia based on susceptibility to the Ponzo illusion, cognitive impairment degree (BACS T-score) and severity of mental state during therapy (Total PANSS score) and to examine the relationship between clinical parameters and the value of the illusion. Patients and methods: a prospective six-week observational study included 30 patients with the paranoid form of schizophrenia in the second week of stable antipsychotic monotherapy, 11 of whom dropped out due to exclusion criteria. At the second and eighth weeks of treatment, patients were assessed for susceptibility to the Ponzo illusion, cognitive impairment using a battery of BACS tests, and severity of mental status during a semi-structured interview using the PANSS scale. Results: the cluster analysis identified 2 clusters of patients who differed in their susceptibility to the Ponzo illusion. Patients in the first cluster (n = 9) with a significantly higher score on negative PANSS symptoms and marked cognitive impairment in the second and eighth weeks of therapy were prone to overestimate the Ponzo illusion, while patients in the second cluster (n = 10) were less susceptible to the Ponzo illusion. Conclusions: this study allowed us to identify two clusters of patients differing in the severity of cognitive and visual impairments, the relationship of susceptibility to Ponzo illusion with such clinical indicators as negative and cognitive symptoms was demonstrated, which confirms the informative value of using the visual illusion methodology as a marker of mental state.

Social Cognition and Apathy between Two Cognitive Subtypes of Schizophrenia: Are There the Same or Different Profiles?

Social Cognition and Apathy between Two Cognitive Subtypes of Schizophrenia: Are There the Same or Different Profiles?

Genetic and Structural Brain Correlates of Cognitive Subtypes Across Youth at Family Risk for Schizophrenia and Bipolar Disorder.

Cognitive impairment is an important feature of Schizophrenia (SZ) and Bipolar Disorder (BP) with severity across the two disorders characterized by significant heterogeneity. Youth at family risk for SZ and BP were clustered based on cognitive function and examined in terms of the clinical, genetic, and brain imaging correlates of cluster membership. One hundred sixty participants, 32 offspring of patients with SZ, 59 offspring of patients with BP and 69 offspring of healthy control parents underwent clinical and cognitive assessments, genotyping and structural MRI. K-means clustering was used to group family risk participants based on cognitive measures. Clusters were compared in terms of cortical and subcortical brain measures as well as polygenic risk scores. Participants were grouped in 3 clusters with intact, intermediate, and impaired cognitive performance. The intermediate and impaired clusters had lower total brain surface area compared with the intact cluster, with prominent localization in frontal and temporal cortices. No between-cluster differences were identified in cortical thickness and subcortical brain volumes. The impaired cluster also had poorer psychosocial functioning and worse PRS-COG compared with the other 2 clusters and with offspring of healthy control parents, while there was no significant between-cluster difference in terms of PRS-SZ and PRS-BP. PRS-COG predicted psychosocial functioning, yet this effect did not appear to be mediated by an effect of PRS-COG on brain area. Stratification based on cognition may help to elucidate the biological underpinnings of cognitive heterogeneity across SZ and BP risk.

Writing Disorders of Children With Developmental Dyslexia in Japanese: Scale Construction and Examination of Cognitive Deficits and Subtypes

本研究は，小学校教員に対する質問紙調査により，（1）日本語のディスレクシア児の書字に関する特徴的な認知障害を包括的に検討すること，（2）それらの認知障害を測定する尺度を作成し，その信頼性・妥当性を検討すること，（3）日本語のディスレクシアの書字障害にはどのようなサブタイプが存在するのかを明らかにすること，（4）各々のサブタイプは読み書き能力とどのように関係しているのかを検討することを目的とした。書字特性の因子分析の結果から，日本語のディスレクシア児では書字に関して4つの主要な認知障害――心的辞書障害，視覚性障害，音韻性障害，書字運動障害――が存在すること，および，これらの認知障害を測定する「ディスレクシア児の書字障害尺度」（WDS-DC）は，信頼性・妥当性が高いことが示唆された。さらに，クラスタ分析により発達性書字障害のサブタイプを分析したところ，重度多重障害群，中度多重障害群，視覚処理障害群が存在することが示唆され，重度多重障害群と中度多重障害群は全ての文字種の読み書き能力において，視覚処理障害群，ボーダー群，障害なし群より低いことが示された。

Determinants of cognitive impairment in multiple system atrophy: Clinical and genetic study.

Classically, cognitive impairment (CI) was not considered as a paramount feature of multiple system atrophy(MSA) in both parkinsonian(MSA-P) and cerebellar(MSA-C) motor-subtypes. Yet, growing evidence indicates currently the commonness of such deficits among MSA patients in different populations. Our aim was to evaluate the cognitive profile of MSA Tunisian patients and to analyze the underlying clinical and genetic determinants. In a retrospective cross-sectional study, clinically-diagnosed MSA patients were included. All subjects underwent clinical and neuropsychological assessments to characterize their cognitive profile. The associations with their APOE genotype status were analyzed. Determinant of CI were specified. We included 71 MSA patients. Female gender(sex-ratio = 0.65) and MSA-P subtype(73%) were predominant. Mean age of disease onset was 59.1years. CI was found in 85.7% of patients(dementia in 12.7% and Mild cognitive impairment(MCI) in 73% of patients mainly of multiple-domain amnestic type(37.3%)). Mean MMSE score was lower among MSA-P compared to MSA-C(23.52 vs. 26.47;p = 0.027). Higher postural instability gait disorder(PIGD) and MDS-UPDRS-III scores were noted in demented MSA patients(p = 0.019;p = 0.015 respectively). The main altered cognitive domain was attention(64.8%). Executive functions and mood disorders were more affected in MSA-P(p = 0.029,p = 0.035 respectively). Clinical and neurophysiological study of dysautonomia revealed no differences across cognitive subtypes. APOE genotyping was performed in 51 MSA patients with available blood samples. Those carrying APOEε4 had 1.32 fold higher risk to develop CI, with lower MMSE score(p = 0.0001). Attention and language were significantly altered by adjusting the p value to APOEɛ4 carriers(p = 0.046 and p = 0.044 respectively). Executive dysfunction was more pronounced among MSA-PAPOEε4 carriers(p = 0.010). In this study, the main determinants of CI in Tunisian MSA patients were MSA-P motor-subtype, mainly of PIGD-phenotype, disease duration and APOEε4 carrying status, defining a more altered cognitive phenotype. This effect mainly concerned executive, attention and language functions, all found to be more impaired in APOEε4 carriers with variable degrees across MSA motor-subtypes.

Coping in Mid- to Late Life and Risk of Mild Cognitive Impairment Subtypes and Dementia: A JPHC Saku Mental Health Study.

The relationship between coping in mid- to late life and cognitive functions remains unclear. To investigate the relationship between habitual coping behaviors of a large Japanese population in their mid- to late-lives and their risk of cognitive decline 15 years later. Overall 1,299 participants were assessed for coping behaviors (in 2000) and cognition (2014-2015). We used the Stress and Coping Inventory to assess the frequency of six coping behaviors (i.e., consulting, planning, positive reappraisal, avoidance, fantasizing, and self-blame). Logistic regression analyses were conducted to examine odds ratios (ORs) for the diagnosis of mild cognitive impairment (MCI), MCI subtypes (single- and multiple-domain MCI), and dementia for coping behaviors. Among the eligible 1,015 participants (72.6 [SD = 5.5] years old in 2014-2015), the numbers for cognitively normal, single-domain MCI, multiple-domain MCI, and dementia were 650 (64.0%), 116 (11.4%), 213 (21.0%), and 36 (3.5%), respectively. Among the six coping behaviors, avoidant coping was significantly associated with noticeable cognitive decline (multiple-domain MCI and dementia). This association remained significant after adjusting for sex, age, education, diagnosis of current major depressive disorder, past history of ischemic heart disease, diabetes, regular alcohol consumption, and smoking (OR = 2.52, 95% CI = 1.23 to 5.15). No significant association with other coping behaviors was found. Avoidant coping in mid- and late life is associated with cognitive decline among older people.

Serum Homocysteine, Vitamin B12, Folate, and Their Association with Mild Cognitive Impairment and Subtypes of Dementia.

Although elevated levels of homocysteine (Hcy) are associated with cognitive impairment and dementia, the relevance of Hcy, vitamin B12, and folate levels to subtypes of dementia are still unknown. To investigate the changes of Hcy, vitamin B12, and folate levels in mild cognitive impairment (MCI) and subtypes of dementia including Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and Lewy body dementia (LBD), and their relationships with cognitive function and magnetic resonance imaging (MRI) markers. We measured serum levels of Hcy, vitamin B12, and folate in 257 subjects. Each subject underwent cognitive function assessment and brain MRI test. The Fazekas and temporal lobe atrophy (MTA) visual rating scales were used to assess the degree of white matter hyperintensities and MTA, respectively. Serum levels of Hcy was higher and vitamin B12 was lower in AD, VaD, FTD, and LBD groups than cognitively normal controls. No significant differences of folate levels were found among 6 groups. Hcy levels were positively correlated with MTA total score in AD (r = 0.448, p < 0.001). Vitamin B12 levels were positively correlated with MoCA in VaD (r = 0.497), and negatively correlated with MTA total score in AD (r = - 0.325) (ps < 0.05). Hyperhomocysteinemia may increase the risk of AD (OR = 2.744), VaD (OR = 3.600), and FTD (OR = 3.244) in the adjusted model (ps < 0.05). Hcy and vitamin B12 levels are associated with MTA in AD. Vitamin B12 levels are associated with general cognition in VaD. Hyperhomocysteinemia is a risk factor for not only AD and VaD but also FTD.

Identifying and revealing different brain neural activities of cognitive subtypes in early course schizophrenia.

BackgroundCognitive subtypes of schizophrenia may exhibit different neurobiological characteristics. This study aimed to reveal the underlying neurobiological features between cognitive subtypes in the early course of schizophrenia (ECS). According to prior studies, we hypothesized to identify 2–4 distinct cognitive subtypes. We further hypothesized that the subtype with relatively poorer cognitive function might have lower brain spontaneous neural activity than the subtype with relatively better cognitive function.MethodCognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Resting-state functional magnetic resonance imaging scanning was conducted for each individual. There were 155 ECS individuals and 97 healthy controls (HCs) included in the subsequent analysis. Latent profile analysis (LPA) was used to identify the cognitive subtypes in ECS individuals, and amplitude of low-frequency fluctuations (ALFFs) was used to measure brain spontaneous neural activity in ECS individuals and HCs.ResultsLPA identified two cognitive subtypes in ECS individuals, containing a severely impaired subtype (SI, n = 63) and a moderately impaired subtype (MI, n = 92). Compared to HCs, ECS individuals exhibited significantly increased ALFF in the left caudate and bilateral thalamus and decreased ALFF in the bilateral medial prefrontal cortex and bilateral posterior cingulate cortex/precuneus (PCC/PCu). In ECS cognitive subtypes, SI showed significantly higher ALFF in the left precentral gyrus (PreCG) and lower ALFF in the left PCC/PCu than MI. Furthermore, ALFFs of left PreCG were negatively correlated with several MCCB cognitive domains in ECS individuals, while ALFF of left PCC/PCu presented opposite correlations.ConclusionOur findings suggest that differences in the brain spontaneous neural activity of PreCG and PCC/PCu might be the potential neurobiological features of the cognitive subtypes in ECS, which may deepen our understanding of the role of PreCG and PCC/PCu in the pathogenesis of cognitive impairment in schizophrenia.

Imaging markers of cerebral amyloid angiopathy and hypertensive arteriopathy differentiate Alzheimer disease subtypes synergistically

BackgroundBoth cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are related to cognitive impairment and dementia. This study aimed to clarify CAA- and HA-related small vessel disease (SVD) imaging marker associations with cognitive dysfunction and Alzheimer disease (AD) subtypes.MethodsA sample of 137 subjects with clinically diagnosed late-onset AD identified from the dementia registry of a single center from January 2017 to October 2021 were enrolled. Semi-quantitative imaging changes (visual rating scale grading) suggestive of SVD were analyzed singularly and compositely, and their correlations with cognitive domains and AD subtypes were examined.ResultsPatients with typical and limbic-predominant AD subtypes had worse cognitive performance and higher dementia severity than minimal-atrophy subtype patients. Deep white matter hyperintensity (WMH) presence correlated inversely with short-term memory (STM) performance. The three composite SVD scores correlated with different cognitive domains and had distinct associations with AD subtypes. After adjusting for relevant demographic factors, multivariate logistic regression (using minimal-atrophy subtype as the reference condition) revealed the following: associations of the typical subtype with periventricular WMH [odds ratio (OR) 2.62; 95% confidence interval (CI), 1.23–5.57, p = 0.012], global SVD score (OR 1.67; 95%CI, 1.11–2.52, p = 0.009), and HA-SVD score (OR 1.93; 95%CI, 1.10–3.52, p = 0.034); associations of limbic-predominant subtype with HA-SVD score (OR 2.57; 95%CI, 1.23–5.37, p = 0.012) and most global and domain-specific cognitive scores; and an association of hippocampal-sparing subtype with HA-SVD score (OR 3.30; 95%CI, 1.58–6.85, p = 0.001).ConclusionComposite SVD imaging markers reflect overall CAA and/or HA severity and may have differential associations with cognitive domains and AD subtypes. Our finding supports the possibility that the clinical AD subtypes may reflect differing burdens of underlying CAA and HA microangiopathologies.

Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data

BackgroundParkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. MethodsCross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. ResultsOur multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. ConclusionsThree distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.

235 Phenotypes of cognitive dysfunction in adults with atopic dermatitis

Importance: Atopic Dermatitis (AD) was recently shown to be associated with cognitive dysfunction in adults. Yet, little is known about the patterns of cognitive deficits experienced by patients suffering from AD. Objective: To investigate the phenotypes of cognitive deficits and their predictors in adults with AD. Methods: A prospective dermatology practice-based study was performed using questionnaires and evaluation by a dermatologist (n=195). Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8-item Short-Form. Results: Latent class analyses identified 4 major cognitive subtypes in adults with AD: normal cognition (71.88%), concentration deficit (14.64%), moderate cognitive impairment (CI; 7.71%), and severe CI (5.77%). Patients with severe CI at baseline were more likely to have persistent CI over time (60.06%) than those with moderate CI (25.39%) or concentration deficit (0.00%). Patients with a concentration deficit, moderate, and severe CI were more likely to have moderate-severe SCORing AD (SCORAD; 77.78%, 90.48% and 75.00% vs 59.05%; p=0.03), moderate depression (Patient Health Questionnaire [PHQ]-9; 35.71%, 50.00% and 83.33% vs 8.57% PHQ9; p<0.0001), and severely impacted quality of life (Dermatology Life Quality Index [DLQI]; 57.14%, 57.14% and 66.67% vs 27.86%; p= 0.008) compared to those with normal cognitive function. Patients with moderate and severe CI additionally reported more severe skin pain (38.10% and 83.33% vs 19.39%; p<0.0001). Conclusions: Three distinct phenotypes of cognitive dysfunction were identified in adults with AD. The occurrence of depression, a severely impacted quality of life and skin pain increased with increasing levels of cognitive dysfunction.

Systematic review of data-driven cognitive subtypes in Parkinson disease.

Recent application of the mild cognitive impairment concept to Parkinson disease (PD) has proven valuable in identifying patients at risk of dementia. However, it has sparked controversy regarding the existence of cognitive subtypes. The present review evaluates the current literature pertaining to data-driven subtypes of cognition in PD. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, systematic literature searches for peer-reviewed articles on the topic of cognitive subtyping in PD were performed. Twenty-two relevant articles were identified in the systematic search. Subtype structures showed either a spectrum of severity or specific domains of impairment. Domain-specific subtypes included amnestic/nonamnestic, memory/executive, and frontal/posterior dichotomies, as well as more complex structures with less definitive groupings. Preliminary longitudinal evidence showed some differences in cognitive progression among subtypes. Neuroimaging evidence provided insight into distinct patterns of brain alterations among subtypes. Recurring phenotypes in the literature suggest strong clinical relevance of certain cognitive subtypes in PD. Although the current literature is limited, it raises critical questions about the utility of data-driven methods in cognitive research. The results encourage further integration of neuroimaging research to define the latent neural mechanisms behind divergent subtypes. Although there is no consensus, there appears to be growing consistency and inherent value in identifying cognitive subtypes in PD.

Social cognitive heterogeneity in schizophrenia: A cluster analysis

This study examined social cognitive heterogeneity in Norwegian sample of individuals with schizophrenia (n = 82). They were assessed with three social cognitive tests: Emotion in Biological Motion (emotion processing), Relationships Across Domains (social perception), and Movie for the Assessment of Social Cognition (theory of mind). Hierarchical and k-means cluster analyses using standardized scores on these three tests provided two clusters. The first cluster (68 %) had mild social cognitive impairments (<0.5 standard deviations below healthy comparison participants). The second cluster (32 %) had severe social cognitive impairments (>2 standard deviations below healthy comparison participants). Validity of the two social cognitive subgroups was indicated by significant differences in functioning, symptom load and nonsocial cognition. Our study shows that social cognitive tests can be used for clinical and cognitive subtyping. This is of potential relevance for treatment.

Interactive effects of polygenic risk and cognitive subtype on brain morphology in schizophrenia spectrum and bipolar disorders

Grey matter volume (GMV) may be associated with polygenic risk for schizophrenia (PRS-SZ) and severe cognitive deficits in people with schizophrenia, schizoaffective disorder (collectively SSD), and bipolar disorder (BD). This study examined the interactive effects of PRS-SZ and cognitive subtypes of SSD and BD in relation to GMV. Two-step cluster analysis was performed on 146 clinical cases (69 SSD and 77 BD) assessed on eight cognitive domains (verbal and visual memory, executive function, processing speed, visual processing, language ability, working memory, and planning). Among them, 55 BD, 51 SSD, and 58 healthy controls (HC), contributed to focal analyses of the relationships between cognitive subtypes, PRS-SZ and their interaction on GMV. Two distinct cognitive subtypes were evident among the combined sample of cases: a ‘cognitive deficit’ group (CD; N = 31, 20SSD/11BD) showed severe impairment across all cognitive indices, and a ‘cognitively spared’ (CS; N = 75; 31SSD/44BD) group showed intermediate cognitive performance that was significantly worse than the HC group but better than the CD subgroup. A cognitive subgroup-by-PRS-SZ interaction was significantly associated with GMV in the left precentral gyrus. Moderation analyses revealed a significant negative relationship between PRS-SZ and GMV in the CD group only. At low and average (but not high) PRS-SZ, larger precentral GMV was evident in the CD group compared to both CS and HC groups, and in the CS group compared to HCs. This study provides evidence for a relationship between regional GMV changes and PRS-SZ in psychosis spectrum cases with cognitive deficits, but not in cases cognitively spared.

Motoric Cognitive Risk Syndrome, Subtypes and 8-Year All-Cause Mortality in Aging Phenotypes: The Salus in Apulia Study.

Background: This study aims to establish the key clinical features of different motoric cognitive risk (MCR) subtypes based on individual quantitative measures of cognitive impairment and to compare their predictive power on survival over an 8-year observation time. Methods: We analyzed data from a population-based study of 1138 subjects aged 65 years and older in south Italy. These individuals were targeted and allocated to subtypes of the MCR phenotype according to the slowness criterion plus one other different cognitive domain for each characterized phenotype (Subjective Cognitive Complaint [SCC]; Global Function [Mini Mental State Examination (MMSE) < 24]; or a combination of both). Clinical evaluation and laboratory assays, along with a comprehensive battery of neuropsychological and physical tests, completed the sample investigation. Results: MCR prevalence was found to be 9.8% (n = 112), 3.6% (n = 41), 3.4% (n = 39) and 1.8% (n = 21) for the MCR, MCR-GlobalFunction, MCR-StructuredSCC and MCR-SCC and GlobalFunction, respectively. Univariate Cox survival analysis showed an association only of the MCR-GlobalFunction subtype with an almost three-fold increased risk of overall death as compared to the other counterparts (HR 2.53, 95%CI 1.28 to 4.99) over an 8-year observation period. Using Generalized Estimating Equations (GEE) for clustered survival data, we found that MCR males had an increased and significant mortality risk with respect to MCR female subjects. Conclusions: MCR phenotypes assigned to the MMSE cognitive domain are more likely to have an increased risk of overall mortality, and gender showed a huge effect on the risk of death for MCR subjects over the 8-year observation.