Discovering Modality of Cognitive Function Using Clustering Analysis

Abstract In this study with Long Life Family Study (LLFS) participants, we aimed to identify patterns of performance on cognitive function assessments as specific cognitive signatures. We hypothesize that such signatures can be correlated with biomarkers and clinical outcomes. More than 4,700 LLFS participants were administered, at enrollment, a series of neuropsychological tests that measure various cognitive domains. We performed a cluster analysis to group LLFS subjects into clusters characterized by combinations of six neuropsychological test scores. The analysis resulted in 10 clusters of varying size with different cognitive signatures that (1) significantly correlated with physical and pulmonary function, and 31 blood biomarkers and (2) predicted mortality and incident medical events such as dementia, cardiovascular diseases, etc. We conclude that cluster analysis of multiple neuropsychological tests discovers cognitive signatures that are more specific than individual cognitive domains and that these can be correlated with blood biomarkers, incident medical outcomes and mortality.

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INTEGRATIVE ANALYSIS OF LONGITUDINAL CHANGES OF NEUROPSYCHOLOGICAL TESTS IN LONG LIFE FAMILY STUDY PARTICIPANTS

Innovation in Aging ◽

10.1093/geroni/igy023.1510 ◽

2018 ◽

Vol 2 (suppl_1) ◽

pp. 404-405

Author(s):

P Sebastiani ◽

S L Andersen ◽

B Sweigart ◽

S Cosentino ◽

B Thyragajan ◽

...

Keyword(s):

Neuropsychological Tests ◽

Family Study ◽

Integrative Analysis ◽

Longitudinal Changes ◽

Long Life ◽

Study Participants

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Determining Filipino Normative Data for a Battery of Neuropsychological Tests: The Filipino Norming Project (FNP)

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000500519 ◽

2019 ◽

Vol 9 (2) ◽

pp. 260-270

Author(s):

Jacqueline Cotoong Dominguez ◽

Thien Kieu Thi Phung ◽

Ma. Fe Payno de Guzman ◽

Krizelle Cleo Fowler ◽

Macario Reandelar Jr ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neuropsychological Tests ◽

Normative Data ◽

Neuropsychological Test ◽

Test Battery ◽

Cognitive Domains ◽

Neuropsychological Test Battery ◽

The Mean ◽

Effect Of Age

Background: Filipino normative data for neuropsychological tests are lacking. Objectives: This study aimed to determine the Filipino normative data for the Filipino Norming Project (FNP) Neuropsychological Battery, combining the Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog) and the Neuropsychological Test Battery from the Uniform Dataset of Alzheimer’s Disease Center (UDS-ADC). Methods: We recruited participants 60 years and older with normal cognition (MMSE score of 25 and above and did not fulfill criteria for dementia according to DSM-IV criteria). Psychologists administered the tests to the study participants. We conducted multivariate analyses to study the effect of age, gender, and education on test performance. Results: A total of 191 participants underwent the FNP Neuropsychological Test Battery. The mean age was 68.8 years (SD 5.4). The majority were female (84.1%). The mean score of ADAS-Cog was 9.98 (SD 4.74). The effect of education was prominent throughout the cognitive domains tested while the effect of age was limited to a few cognitive domains. The mean ADAS-Cog scores were 11.80 ± 4.40 for primary education, 9.93 ± 5.08 for secondary, and 8.15 ± 3.95 for tertiary. On average, women scored 2.75 points lower than men and performed better on the verbal components. Men performed better on the constructional praxis component. The same effect of education and gender was observed for the UDS-ADC. Conclusion: For the first time, normative data are available for the ADAS-Cog and UDS-ADC for a Filipino older population. This study stresses the importance of establishing population-specific normative data, taking into account the specific sociocultural and linguistic context of that population.

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Changes of Regional Neural Activity Homogeneity in Preclinical Alzheimer’s Disease: Compensation and Dysfunction

Frontiers in Neuroscience ◽

10.3389/fnins.2021.646414 ◽

2021 ◽

Vol 15 ◽

Author(s):

Zhen Zhang ◽

Liang Cui ◽

Yanlu Huang ◽

Yu Chen ◽

Yuehua Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Frontal Lobe ◽

Temporal Lobe ◽

Neural Activity ◽

Neuropsychological Tests ◽

Parietal Lobe ◽

Neuropsychological Test ◽

Potential Biomarker

IntroductionSubjective cognitive decline (SCD) is the preclinical stage of Alzheimer’s disease and may develop into amnestic mild cognitive impairment (aMCI). Finding suitable biomarkers is the key to accurately identifying SCD. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies on SCD patients showed functional connectivity disorders. Our goal was to explore whether local neurological homogeneity changes in SCD patients, the relationship between these changes and cognitive function, and similarities of neurological homogeneity changes between SCD and aMCI patients.Materials and Methods37 cases of the healthy control (HC) group, 39 cases of the SCD group, and 28 cases of the aMCI group were included. Participants underwent rs-fMRI examination and a set of neuropsychological test batteries. Regional homogeneity (ReHo) was calculated and compared between groups. ReHo values were extracted from meaningful regions in the SCD group, and the correlation between ReHo values with the performance of neuropsychological tests was analyzed.ResultsOur results showed significant changes in the ReHo among groups. In the SCD group compared with the HC group, part of the parietal lobe, frontal lobe, and occipital lobe showed decreased ReHo, and the temporal lobe, part of the parietal lobe and the frontal lobe showed increased ReHo. The increased area of ReHo was negatively correlated with the decreased area, and was related to decrease on multiple neuropsychological tests performance. Simultaneously, the changed areas of ReHo in SCD patients are similar to aMCI patients, while aMCI group’s neuropsychological test performance was significantly lower than that of the SCD group.ConclusionThere are significant changes in local neurological homogeneity in SCD patients, and related to the decline of cognitive function. The increase of neurological homogeneity in the temporal lobe and adjacent area is negatively correlated with cognitive function, reflecting compensation for local neural damage. These changes in local neurological homogeneity in SCD patients are similar to aMCI patients, suggesting similar neuropathy in these two stages. However, the aMCI group’s cognitive function was significantly worse than that of the SCD group, suggesting that this compensation is limited. In summary, regional neural activity homogeneity may be a potential biomarker for identifying SCD and measuring the disease severity.

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Association Between APOE Alleles and Change of Neuropsychological Tests in the Long Life Family Study

Journal of Alzheimer s Disease ◽

10.3233/jad-201113 ◽

2021 ◽

Vol 79 (1) ◽

pp. 117-125

Author(s):

Mengtian Du ◽

Stacy L. Andersen ◽

Nicole Schupf ◽

Mary F. Feitosa ◽

Megan S. Barker ◽

...

Keyword(s):

Older Adults ◽

Cognitive Function ◽

Test Scores ◽

Healthy Aging ◽

Family Study ◽

Apoe Genotype ◽

Cognitive Test ◽

Cross Sectional ◽

Long Life ◽

E4 Allele

Background: The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective: To test whether APOE genotype is associated with change of cognitive function in older adults. Methods: We used Bayesian hierarchical models to test the association between APOE alleles and change of cognitive function. Six longitudinally collected neuropsychological test scores were modelled as a function of age at enrollment, follow-up time, gender, education, field center, birth cohort indicator (≤1935, or >1935), and the number of copies of ɛ2 or ɛ4 alleles. Results: Out of 4,587 eligible participants, 2,064 were male (45.0%), and age at enrollment ranged from 25 to 110 years, with mean of 70.85 years (SD: 15.75). We detected a significant cross-sectional effect of the APOE ɛ4 allele on Logical Memory. Participants carrying at least one copy of the ɛ4 allele had lower scores in both immediate (–0.31 points, 95% CI: –0.57, –0.05) and delayed (–0.37 points, 95% CI: –0.64, –0.10) recall comparing to non-ɛ4 allele carriers. We did not detect any significant longitudinal effect of the ɛ4 allele. There was no cross-sectional or longitudinal effect of the ɛ2 allele. Conclusion: The APOE ɛ4 allele was identified as a risk factor for poorer episodic memory in older adults, while the APOE ɛ2 allele was not significantly associated with any of the cognitive test scores.

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A Hypothesis-Generating Study Using Electrophysiology to Examine Cognitive Function in Colon Cancer Patients

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz051 ◽

2019 ◽

Vol 35 (2) ◽

pp. 226-232 ◽

Cited By ~ 1

Author(s):

Stanley Hughwa Hung ◽

Sumeet Mutti Jaswal ◽

Sarah Elizabeth Neil-Sztramko ◽

Julia W Y Kam ◽

Negin Niksirat ◽

...

Keyword(s):

Colon Cancer ◽

Cognitive Function ◽

Cancer Patients ◽

Sustained Attention ◽

Test Performance ◽

Neuropsychological Tests ◽

Neuropsychological Test ◽

Mind Wandering ◽

Event Related Potential ◽

Change In Mean

Abstract Introduction The purpose of this study was to describe the trajectory of cognitive function using neuropsychological tests and electrophysiological measures in individuals receiving 5FU/oxaliplatin chemotherapy for colon cancer. Methods A total of 10 participants were tested at baseline (within 3 weeks of starting chemotherapy), 6 months (coinciding with the end of chemotherapy treatment), and 12 months (approximately 6 months post-chemotherapy). Participants completed neuropsychological tests and electrophysiology recordings of P300 event-related potential (ERP) elicited by a sustained attention to response task paired with experience sampling of attentional states (subjective reports of on-task or mind wandering). Results No change in mean neuropsychological test performance was observed. Comparison of mean P300 ERP amplitudes as a function of attentional states (on-task vs. mind wandering) revealed no main effect of attentional state observed at baseline or 6 months, but a significant effect of attention was observed at 12 months, consistent with effects observed in healthy individuals. Conclusions Future studies can consider sustained attention constructs when studying cognitive function in colon cancer patients.

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Pathway Analysis of Leisure Activity and Cognitive Function in the Long Life Family Study

Innovation in Aging ◽

10.1093/geroni/igaa057.1618 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 501-501

Author(s):

Nicole Roth ◽

Paola Sebastiani ◽

Stephanie Cosentino ◽

Nicole Schupf ◽

Thomas Perls ◽

...

Keyword(s):

Cognitive Function ◽

Cognitive Reserve ◽

Family Study ◽

Verbal Learning ◽

Family Members ◽

Leisure Activity ◽

Cognitive Test ◽

Long Life ◽

Age And Sex ◽

Familial Longevity

Abstract Familial longevity and greater involvement in activities purported to build cognitive reserve (e.g. education, cognitively stimulating leisure activity) have both been associated with better cognitive function in later life, yet little is known about how these protective factors relate with one another. In this work, we modeled the associations among familial longevity, proxies of cognitive reserve, and cognitive function in the Long Life Family Study (LLFS). We assessed cognitive function using a comprehensive battery of neuropsychological tests (i.e. Digit-Spans, California Verbal Learning Test, Rey-Osterrieth Complex Figure, phonemic fluency, category fluency, Word Generation, DKEFS Sorting Test, and logical memory) in a subset of LLFS family members and a referent cohort (N=314, mean age 75.7±14.6 years). To model these associations, we used a series of Bayesian hierarchical regression pathways that incorporate a random effect for family relatedness, adjusted by age and sex. All continuous variables were rescaled and bounded to be approximately between (0,1) in order to standardize regression coefficients and to allow for an asymmetrical beta-distribution. Controlling for education level, age, and sex, referents had greater engagement in late-life cognitive activities compared to LLFS family members, β=0.38 (95% CI: 0.18 to 0.57). In turn, those with higher markers of cognitive reserve exhibited better neuropsychological performance. Despite LLFS family members having lower participation in cognitively stimulating leisure activities, there were no differences between LLFS family members and referents on cognitive test performance. These results suggest long-lived family members may have more unique pathways (i.e. genetic/environmental) that preserve cognition later in life.

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Empirical Evidence for Cognitive Subgroups in Body Dysmorphic Disorder

10.1101/2020.06.29.20143073 ◽

2020 ◽

Author(s):

Amy Malcolm ◽

Sarah N. Brennan ◽

Sally A. Grace ◽

Toni D. Pikoos ◽

Wei Lin Toh ◽

...

Keyword(s):

Working Memory ◽

Social Cognition ◽

Cognitive Function ◽

Cognitive Functioning ◽

Clustering Analysis ◽

Body Dysmorphic Disorder ◽

Visual Learning ◽

List Type ◽

Healthy Controls ◽

Cognitive Domains

AbstractObjectiveCurrent understanding of cognitive functioning in body dysmorphic disorder (BDD) is limited, owing to few studies, small sample sizes, and assessment across only limited cognitive domains. Existing research has also shown inconsistent findings, with both intact and impaired cognition reported in BDD, which might point toward cognitive heterogeneity in the disorder. This study aimed to examine the cognitive profile of BDD in a large sample across eight cognitive domains, and to explore whether cognitive subgroups might be identified within BDD.MethodsCognitive domains of inhibition/flexibility, working memory, speed of processing, reasoning and problem-solving, visual and verbal learning, attention/vigilance and social cognition were assessed and compared between 65 BDD patients and 70 healthy controls. Then, hierarchical clustering analysis was conducted on the BDD group’s cognitive data.ResultsGroup-average comparisons demonstrated significantly poorer cognitive functioning in BDD than healthy controls in all domains except for attention/vigilance and social cognition. Cluster analysis identified two divergent cognitive subgroups within our BDD cohort characterised by i) broadly intact cognitive function with mild selective impairments (72.3%), and ii) broadly impaired cognitive function (27.7%). However, the clusters did not significantly differ on clinical parameters or most sociodemographic characteristics.ConclusionCognitively diverse subgroups were identified within BDD, yet these were obscured in group-average comparisons. However, subgroup profiles of cognitive functioning seem unrelated to the clinical presentation of BDD. Further research into the underlying mechanisms of cognition in BDD is warranted.Significant OutcomesCognitive function varies widely among people with body dysmorphic disorder (BDD) and includes subgroups characterised by broadly intact or broadly impaired cognitive profiles.However, reduced performances in visual learning and working memory as relative to healthy participants were identified across both BDD cognitive subgroups to differing degrees.Clinical characteristics were not significantly different among the two BDD cognitive subgroups; what role cognitive functioning may play in the aetiology or presentation of BDD remains unclear.LimitationsThe output of clustering analysis is sensitive to the choice of variables entered and requires replication with analogous measures of cognition.Psychiatric comorbidities and medications could have impacted cognitive performances in the BDD group in an unaccounted-for manner.Data availability statementAuthor elects to not share data.

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An Evaluation of DNA Methyltransferase 1 (DNMT1) Single Nucleotide Polymorphisms and Chemotherapy-Associated Cognitive Impairment: A Prospective, Longitudinal Study

Scientific Reports ◽

10.1038/s41598-019-51203-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Alexandre Chan ◽

Angie Yeo ◽

Maung Shwe ◽

Chia Jie Tan ◽

Koon Mian Foo ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cancer Patients ◽

Dna Methyltransferase ◽

Dna Methyltransferases ◽

Breast Cancer Patients ◽

Prospective Longitudinal Study ◽

Cognitive Domains ◽

Prospective Longitudinal

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.

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The Ten Point Clock Test: A Quick Screen and Grading Method for Cognitive Impairment in Medical and Surgical Patients

The International Journal of Psychiatry in Medicine ◽

10.2190/5a0f-936p-vg8n-0f5r ◽

1994 ◽

Vol 24 (3) ◽

pp. 229-244 ◽

Cited By ~ 144

Author(s):

Peter J. Manos ◽

Rae Wu

Keyword(s):

Cognitive Impairment ◽

Cognitive Deficits ◽

Neuropsychological Tests ◽

Medical Center ◽

Neuropsychological Test ◽

Hospitalized Patients ◽

Surgical Patients ◽

Tertiary Referral Center ◽

The Mean ◽

State Examination

Objective: The objective of this study was to evaluate the clinical utility of the ten point clock test in screening for and grading cognitive deficits in medical and surgical patients. Method: The setting was the hospital and clinics of Virginia Mason Medical Center, a tertiary referral center. Consecutive samples of hospitalized patients, and clinic outpatients—with and without a dementia—were administered the ten point clock test as well as a number of other neuropsychological tests and measures of cognitive impairment. Results: Clock scores correlated with neuropsychological test scores and with the mini-mental state examination. They were stable from rater to rater, and from day to day in stable patients. The mean clock score of elderly outpatient controls was 8.5, significantly different from the mean of 5.5 scored by patients with a dementia. A cut off score of seven identified 76 percent of outpatients with dementia and 78 percent of elderly controls. Clock scores correlated well with nurses' ratings of their inpatients' cognitive deficits (Spearman's rs = −0.61). The test was easy to administer, even to hospitalized patients. Conclusions: The ten point clock test is reliable, valid, and useful as a quick screen and grading method for cognitive deficits in medical and surgical patients.

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Neuropsychological Test Performance in Framingham: A Descriptive Study

Psychological Reports ◽

10.1177/0033294187060003-201.1 ◽

1987 ◽

Vol 60 (3_part_2) ◽

pp. 1023-1040

Author(s):

Mary E. Farmer ◽

Lon R. White ◽

Steven J. Kittner ◽

Edith Kaplan ◽

Elizabeth Moes ◽

...

Keyword(s):

Test Performance ◽

Neuropsychological Tests ◽

Language Skills ◽

Community Sample ◽

Neuropsychological Test ◽

Descriptive Study ◽

Community Dwelling ◽

Abstract Thinking ◽

Framingham Study ◽

Hearing Impairments

In 1976–1978, a battery of eight neuropsychologic tests was administered to 2,123 participants in the Framingham Study aged 55 to 89 yr. The battery was designed to sample multiple areas of cognitive function including language skills, memory, learning, reproduction of designs, attention, and abstract thinking. Performance is described for several groups in this population: a large community-dwelling sample, those with hearing impairments, and those with documented strokes. Performance is described by age, sex, and education strata for the community sample. This normative information should be useful for interpreting individual test performance on neuropsychological tests.

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