Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER
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TaubCONNECT Research Perspective:
February 2024



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January 2024:

Risk of Alzheimer's Disease is Associated with Longitudinal Changes in Plasma Biomarkers in the Multi-Ethnic Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP) Cohort


ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease


Benchmarking of Deep Neural Networks for Predicting Personal Gene Expression from DNA Sequence Highlights Shortcomings


TaubCONNECT Research Perspectives: Best Poster Presentations Taub Institute Retreat November 2023


December 2023:

Objective Physical Function in the Alzheimer's Disease Continuum: Association with Cerebrospinal Fluid Biomarkers in the ALBION Study

Racial/Ethnic Disparities in Misidentification of Dementia in Medicare Claims: Results from the Washington Heights-Inwood Columbia Aging Project

Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition in a Sample of Community-Dwelling Older Adults with Dementia

Effects of Lithium on Serum Brain-Derived Neurotrophic Factor in Alzheimer's Patients with Agitation


November 2023:

2023 Taub Institute Grants for Emerging Research (TIGER) Awardees!


September 2023:

Rie1 and Sgn1 Form an RNA-Binding Complex that Enforces the Meiotic Entry Cell Fate Decision

Memory and Language Cognitive Data Harmonization Across the United States and Mexico

Education as a Moderator of Help Seeking Behavior in Subjective Cognitive Decline

August 2023:

Nerve Growth Factor Receptor (Ngfr) Induces Neurogenic Plasticity by Suppressing Reactive Astroglial Lcn2/Slc22a17 Signaling in Alzheimer's Disease

Multicellular Communities are Perturbed in the Aging Human Brain and Alzheimer's Disease

Simple Topological Task-based Functional Connectivity Features Predict Longitudinal Behavioral Change of Fluid Reasoning in the RANN Cohort

The Neuropathological Landscape of Hispanic and non-Hispanic White Decedents with Alzheimer Disease

July 2023:

Caspase-9 Inhibition Confers Stronger Neuronal and Vascular Protection Compared to VEGF Neutralization in a Mouse Model of Retinal Vein Occlusion

The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study Design and Methodology

Heart Failure-Induced Cognitive Dysfunction is Mediated by Intracellular Ca2+ Leak Through Ryanodine Receptor Type 2

June 2023:

Evaluation of Plasma Biomarkers for A/T/N Classification of Alzheimer Disease Among Adults of Caribbean Hispanic Ethnicity

Dietary Flavanols Restore Hippocampal-Dependent Memory in Older Adults with Lower Diet Quality and Lower Habitual Flavanol Consumption

Survey of Neuroanatomic Sampling and Staining Procedures in Alzheimer Disease Research Center Brain Banks

May 2023:

Polygenic Risk Score Penetrance & Recurrence Risk in Familial Alzheimer Disease

Effects of Brain Maintenance and Cognitive Reserve on Age-related Decline in Three Cognitive Abilities

High School Quality is Associated with Cognition 58 Years Later

Older Adults Compensate for Switch, but not Mixing Costs, Relative to Younger Adults on an Intrinsically Cued Task Switching Experiment

April 2023:

Glucocorticoid-Driven Mitochondrial Damage Stimulates Tau Pathology

A Global View of the Genetic Basis of Alzheimer Disease

ARIA in Patients Treated with Lecanemab (BAN2401) in a Phase 2 Study in Early Alzheimer's Disease

March 2023:

CREB3L2-ATF4 Heterodimerization Defines a Transcriptional hub of Alzheimer's Disease Gene Expression Linked to Neuropathology

Healthy Lifestyle Behaviors and Biological Aging in the US National Health and Nutrition Examination Surveys 1999-2018

February 2023:

Microglia Reactivity Entails Microtubule Remodeling from Acentrosomal to Centrosomal Arrays

Genuine Selective Caspase-2 Inhibition with new Irreversible Small Peptidomimetics

Costs During the Last Five Years of Life for Patients with Clinical and Pathological Confirmed Diagnosis of Lewy Body Dementia and Alzheimer's Disease


January 2023:

Histopathology of the Cerebellar Cortex in Essential Rremor and Other Neurodegenerative Motor Disorders: Comparative Analysis of 320 Brains

The Caribbean-Hispanic Alzheimer's Disease Brain Transcriptome Reveals Ancestry-Specific Disease Mechanisms

Comparison of Amyloid Burden in Individuals with Down Syndrome Versus Autosomal Dominant Alzheimer's Disease: A Cross-Sectional Study

Neuronal Membrane Proteasomes Regulate Neuronal Circuit Activity in Vivo and are Required for Learning-Induced Behavioral Plasticity

December 2022:

A Systemic Cell Stress Signal Confers Neuronal Resilience Toward Oxidative Stress in a Hedgehog-Dependent Manner

RNA Methyltransferase NSun2 Deficiency Promotes Neurodegeneration through Epitranscriptomic Regulation of Tau Phosphorylation

Cell Type-Specific Changes Identified by Single-Cell Transcriptomics in Alzheimer's Disease

Brain Aging Among Racially and Ethnically Diverse Middle-Aged and Older Adults

Association of Subjective Cognitive Decline With Progression to Dementia in a Cognitively Unimpaired Multiracial Community Sample

November 2022:

First Place: CREB3L2-ATF4 Heterodimerization Defines a Transcriptional Hub of Alzheimer's Disease Gene Expression Linked to Neuropathology

First Place: Neuroproteasome Localization and Dysfunction Modulate Pathology in Alzheimer's Disease

October 2022:

Clearance of an Amyloid-Like Translational Repressor is Governed by 14-3-3 Proteins

Diet Moderates the Effect of Resting State Functional Connectivity on Cognitive Function

Longitudinal Patterns of Cortical Atrophy on MRI in Patients With Alzheimer Disease With and Without Lewy Body Pathology

September 2022:

Crosstalk Between Acetylation and the Tyrosination/Detyrosination Cycle of α-Tubulin in Alzheimer's Disease

Deep Learning of MRI Contrast Enhancement for Mapping Cerebral Blood Volume from Single-Modal Non-Contrast Scans of Aging and Alzheimer's Disease Brains

Socioeconomic Status, Biological Aging, and Memory in a Diverse National Sample of Older US Men and Women

August 2022:

Retromer Deficiency in Tauopathy Models Enhances the Truncation and Toxicity of Tau

Aβ42 Oligomers Trigger Synaptic Loss Through CAMKK2-AMPK-Dependent Effectors Coordinating Mitochondrial Fission and Mitophagy

July 2022:

GW5074 Increases Microglial Phagocytic Activities: Potential Therapeutic Direction for Alzheimer's Disease

Cerebral Amyloid Angiopathy Interacts with Neuritic Amyloid Plaques to Promote Tau and Cognitive Decline

Amyloid, Cerebrovascular Disease, and Neurodegeneration Biomarkers Are Associated with Cognitive Trajectories in a Racially and Ethnically Diverse, Community-Based Sample

June 2022:

Genotype-Phenotype Correlation of T Cell Subtypes Reveals Senescent and Cytotoxic Genes in Alzheimer's Disease

Single Cell/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer's Disease

May 2022:

FMNL2 Regulates Gliovascular Interactions and Is Associated with Vascular Risk Factors and Cerebrovascular Pathology in Alzheimer’s Disease

Molecular Insights into Cell Type-Specific Roles in Alzheimer's Disease: Human Induced Pluripotent Stem Cell-Based Disease Modeling

Effects of Eph/Ephrin Signalling and Human Alzheimer's Disease-Associated EphA1 on Drosophila Behaviour and Neurophysiology

April 2022:

Progranulin Mutations in Clinical and Neuropathological Alzheimer's Disease

Wolframin is a Novel Regulator of Tau Pathology and Neurodegeneration

Clinical Trajectories at the End of Life in Dementia Patients With Alzheimer Disease and Lewy Body Neuropathologic Changes

March 2022:

Homotypic Fibrillization of TMEM106B Across Diverse Neurodegenerative Diseases

Correlation of Plasma and Neuroimaging Biomarkers in Alzheimer's Disease

Probing the Proteome to Explore Potential Correlates of Increased Alzheimer's-Related Cerebrovascular Disease in Adults with Down Syndrome

February 2022:

Tubulin Tyrosination Regulates Synaptic Function and is Disrupted in Alzheimer's Disease

Pyramidal Tract Neurons Drive Amplification of Excitatory Inputs to Striatum Through Cholinergic Interneurons

Associations Between Neuropsychiatric Symptoms and Neuropathological Diagnoses of Alzheimer Disease and Related Dementias

Longitudinal Associations Between Racial Discrimination and Hippocampal and White Matter Hyperintensity Volumes Among Older Black Adults

The Penalty of Stress - Epichaperomes Negatively Reshaping the Brain in Neurodegenerative Disorders

January 2022:

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A Resource for Genetic Discovery

Atlas of RNA Editing Events Affecting Protein Expression in Aged and Alzheimer's Disease Human Brain Tissue

The Neuronal Retromer can Regulate Both Neuronal and Microglial Phenotypes of Alzheimer's Disease

Deep Learning Improves Utility of Tau PET in the Study of Alzheimer's Disease

December 2021:

Predictors of Incident Mild Cognitive Impairment and Its Course in a Diverse Community-Based Population

Atlas of RNA Editing Events Affecting Protein Expression in Aged and Alzheimer's Disease Human Brain Tissue

Integration of GWAS and Brain Transcriptomic Analyses in a Multiethnic Sample of 35,245 Older Adults Identifies DCDC2 Gene as Predictor of Episodic Memory Maintenance

November 2021:

KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer's Disease

Characterization of Mitochondrial DNA Quantity and Quality in the Human Aged and Alzheimer's Disease Brain

Self-Awareness for Financial Decision Making Abilities is Linked to Right Temporal Cortical Thickness in Older Adults

October 2021:

An Immune Response Characterizes Early Alzheimer's Disease Pathology and Subjective Cognitive Impairment in Hydrocephalus Biopsies

MEF2C Common Genetic Variation Is Associated With Different Aspects of Cognition in Non-Hispanic White and Caribbean Hispanic Non-demented Older Adults

Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults

Age of Onset of Huntington's Disease in Carriers of Reduced Penetrance Alleles

September 2021:

Traversing the Aging Research and Health Equity Divide: Toward Intersectional Frameworks of Research Justice and Participation

Epigenomic Features Related to Microglia are Associated with Attenuated Effect of APOE ε4 on Alzheimer's Disease Risk in Humans

Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease

August 2021:

Neuropsychological Predictors of Severe Functional Dependency in a Multiethnic Community Cohort of Individuals with Alzheimer's Disease

Midlife Vascular Factors and Prevalence of Mild Cognitive Impairment in Late-Life in Mexico

Effect of Aerobic Exercise on White Matter Tract Microstructure in Young and Middle-Aged Healthy Adults

July 2021:

Quantifying Age-Related Changes in Brain and Behavior: A Longitudinal Versus Cross-Sectional Approach

The Association Between Sex and Risk of Alzheimer's Disease in Adults with Down Syndrome

June 2021:

Marked Mild Cognitive Deficits in Humanized Mouse Model of Alzheimer's-Type Tau Pathology

Rapid ATF4 Depletion Resets Synaptic Responsiveness after cLTP

Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics

Vascular-Derived SPARC and SerpinE1 Regulate Interneuron Tangential Migration and Accelerate Functional Maturation of Human Stem Cell-Derived Interneurons

May 2021:

PAC1 Receptor–Mediated Clearance of Tau in Postsynaptic Compartments Attenuates Tau Pathology in Mouse Brain

Socioeconomic and Psychosocial Mechanisms Underlying Racial/Ethnic Disparities in Cognition Among Older Adults

Recognition Memory and Divergent Cognitive Profiles in Prodromal Genetic Frontotemporal Dementia

April 2021:

Association Between Early Psychotic Symptoms and Alzheimer's Disease Prognosis in a Community-Based Cohort

Complexity and Graded Regulation of Neuronal Cell-Type-Specific Alternative Splicing Revealed by Single-Cell RNA Sequencing

The Microtubule Cytoskeleton at the Synapse & The Synaptic Life of Microtubules

Distinct Cortical Thickness Patterns Link Disparate Cerebral Cortex Regions to Select Mobility Domains

March 2021:

Optimizing Subjective Cognitive Decline to Detect Early Cognitive Dysfunction

The AD Tau Core Spontaneously Self-Assembles and Recruits Full-Length Tau to Filaments

Olfactory Impairment is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease

Race/ethnicity and Gender Modify the Association Between Diet and Cognition in U.S. Older Adults: National Health and Nutrition Examination Survey 2011-2014

Insights Into the Role of Diet and Dietary Flavanols in Cognitive Aging: Results of a Randomized Controlled Trial

February 2021:

Plasma P-Tau181, P-Tau217, and Other Blood-Based Alzheimer's Disease Biomarkers in a Multi-Ethnic, Community Study

Pathogenic Role of Delta 2 Tubulin in Bortezomib-Induced Peripheral Neuropathy




Glucocorticoid Stress Hormones Stimulate Vesicle-Free Tau Secretion and Spreading in the Brain

Dr. Waites
Clarissa Waites, PhD

Exposure to stressful life events and elevated levels of glucocorticoids (GCs), the primary hormones associated with stress, are recognized as significant risk factors for Alzheimer’s disease (AD). A pivotal pathological link between stress and AD appears to be the protein Tau. Stress and elevated GC levels induce Tau pathologies similar to those observed in AD, such as Tau hyperphosphorylation and oligomerization. Moreover, experimental reductions in Tau have been found to offer protection against the neurotoxic effects and cognitive deficits induced by amyloid beta and stress in animals, underscoring the pivotal role of Tau in the neurodegenerative processes linked to AD and prolonged stress.

A hallmark of AD-related Tau pathology is its distinctive pattern of spread among regions of the brain that are anatomically connected, specifically from the entorhinal cortex to the hippocampus, and then to the prefrontal cortex. This pattern of Tau dissemination is closely linked to the degree of cognitive dysfunction observed in AD patients and is considered a critical factor in the disease’s advancement. For more than a decade, research in this area has primarily concentrated on the role of vesicles in the distribution of Tau, yet the vast majority of Tau secreted by neurons ( ~ 90%) is vesicle-free. This non-vesicular secretion pathway and its impact on the spread of Tau pathology are not well understood. Additionally, the exact mechanisms by which stress and GCs may facilitate Tau’s pathological spread remain to be clarified.

Figure. Glucocorticoids induce Tau spreading in the brain, which is blocked by an inhibitor of Tau oligomerization.

Figure. Glucocorticoids induce Tau spreading in the brain, which is blocked by an inhibitor of Tau oligomerization. A-B) Images of human Tau (hTau) spreading in the mouse hippocampus. GFP labels AAV-infected neurons, hTau immunostaining labels neurons with hTau, hTau+/GFP- neurons indicate Tau spreading. The synthetic glucocorticoid dexamethasone (DEX) induces hTau spreading within (A) and beyond (B) hippocampal area CA1, where AAV was injected (see schematic diagram). EGCG, an inhibitor of Tau oligomerization and type 1 unconventional protein secretion, prevents DEX-induced spreading. Yellow boxes indicate enlarged regions. Size bars, 25 um. C-E) Quantification of Tau spreading based on hTau+/GFP- neurons per mm2 (C), GFP/hTau colocalization (D), and maximum spreading distance from the injection site (E). ***P<0.001, ****P<0.0001, one-way ANOVA with multiple comparisons.

In the current study, recently published in Cell Death & Disease, we explored the impact of GCs on Tau secretion and its spread in mouse hippocampal neurons and ex vivo brain slices. We discovered that GCs trigger the release of primarily vesicle-free Tau, a process that is dependent on neural activity and glycogen synthase kinase 3β (GSK3β), occurring via type 1 unconventional protein secretion (UPS). Furthermore, we found that GC treatment enhances Tau spread across the hippocampus, an effect that can be mitigated by blocking Tau aggregation and type 1 UPS using the catechin epigallocatechin gallate. These results suggest that increased levels of GCs facilitate the propagation of Tau, offering insights into how stress and GCs may accelerate cognitive decline in AD.

Clarissa Waites, PhD
Associate Professor of Pathology and Cell Biology and Neuroscience
cw2622@cumc.columbia.edu

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Whole Genome-Wide Sequence Analysis of Long-Lived Families (Long-Life Family Study) Identifies MTUS2 Gene Associated with Late-Onset Alzheimer's Disease

Sandra Barral Rodriguez, PhD

Sandra Barral, PhD

The Long-Life Family Study (LLFS) is an international collaborative study designed to examine the genetic and non-genetic factors associated with exceptional longevity. Previous studies examining the health of LLFS participants have shown that this cohort appears to be healthier than random cohorts of the same age/sex, including lower rates of dementia and memory decline. This exceptionally healthy cohort provides a unique opportunity to investigate the genetic contributions to Late Onset Alzheimer’s Disease (LOAD).

Our study examined the association between whole genome sequence variants and LOAD in 3,475 LLFS members. We further investigated whether the observed LOAD associated LLFS variants generalize to cohorts characterized by different risk of dementia: high risk populations (familial LOAD and Down Syndrome), Alzheimer’s disease referral-base cohort, and population-based cohorts. As recently reported in Alzheimer’s & Dementia, we identified several genetic variants within the MTUS2 gene significantly associated with LOAD. The association was also observed in the six independent cohorts considered and become significantly stronger within high Aβ42/40 ratio compared to lower amyloid ratio.

Figure 1.Manhattan plot of Seq-GWAS results in LLFS cohort.

Figure 1. Manhattan plot of Seq-GWAS results in LLFS cohort. The X-axis represents the genomic position for each of the SNPs analyzed; Y-axis represents the -log10 transformed p-values. The red line indicates the genome-wide significance threshold (p < 5 × 10−8). GWAS, genome-wide association studies; LLFS, Long-Life Family Study; SNP, single nucleotide polymorphism.

MTUS2 is a plus end tracking protein implicated in the development and function of the nervous system. It is expressed in brain during development and adulthood. RNA-seq analysis of more than 1,100 individuals’ post-mortem brains from the Accelerating Medicines Partnership for Alzheimer’s disease (AMP-AD) consortium demonstrated significant change in MTUS2 gene expression when comparing LOAD cases and cognitively healthy samples. Our results support MTUS2 as a novel LOAD risk locus. Future functional validation analyses will be needed to further investigate the role of MTUS2 in LOAD pathology.

Sandra Barral, PhD
Associate Professor of Neurogenetics (in Neurology, the Taub Institute, and the Gertrude H. Sergievsky Center) at CUMC
smb2174@cumc.columbia.edu

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In Vivo Tau is Associated with Change in Memory and Processing Speed, but Not Reasoning, in Cognitively Unimpaired Older Adults

Sharon Sanz Simon, PhD    Yaakov Stern, PhD
Sharon Sanz Simon, PhD    Yaakov Stern, PhD

In vivo neuroimaging biomarkers of tau and amyloid-β pathology have become essential tools in research into normal cognitive aging and preclinical Alzheimer’s disease (AD), as deposition of both proteins begins several years before clinical symptoms emerge. Despite the well-accepted involvement of amyloid-β and tau pathology in AD, questions remain regarding the role of these proteins in age-related cognitive decline. For instance, previous studies found normal aging is associated with the deposition of tau pathology in the medial temporal lobe (MTL) and neocortex even in the absence of or in the context of low amyloid-β pathology. This condition has been termed primary age-related tauopathy and there is still debate as to whether this is part of the AD spectrum or is part of “normal” aging. Previous work reported that tau pathology in transentorhinal regions precedes amyloid-β deposition and tau PET studies indicate a close relationship between patterns of early tau deposition and cognitive impairment.

Figure 4. Scatterplot diagrams illustrating the relationship between tau PET uptake

Figure 4. Scatterplot diagrams illustrating the relationship between tau PET uptake [ 18F-MK-6240] and memory change across brain regions. (A–D) The associations considering regional tau uptake (meta-ROIs). (E) A forest plot representing the unstandardized betas and 95% interval confidence for each linear regression considering 36 brain areas. The results highlighted (*) are not corrected for multiple comparisons. All regressions accounted for age at follow-up, sex/gender, education, and baseline memory performance. Abbreviations: C/P, cingulate/parietal lobe; LTL, lateral temporal lobe; MTL, medial temporal lobe; ROI, region of interest; SUVR, standardized uptake value ratio.

Tau accumulation has been associated with longitudinal cognitive decline, typically in episodic memory. Due to the initial tau accumulation in the MTL, memory has been the domain typically investigated; however, few studies suggest tau accumulation to be associated with a decline in global cognition, executive functions, and speed processing. Therefore, the impact of early tau accumulation on cognitive trajectories beyond memory in cognitively unimpaired older adults still needs to be further characterized and understood, particularly with second-generation tau tracers. For instance, the tracer 18F-MK-6240 is a PET ligand for imaging neurofibrillary tangles in vivo that has shown favorable imaging characteristics and spatial distributions consistent with the neuropathological staging of neurofibrillary tangles in AD in preliminary studies. Studies evaluating 18F-MK-6240 in humans have indicated high affinity to neurofibrillary tangles in AD, minimal off-target binding in the brain, and the presence of extra-axial signals in some cases. In addition, the tracer 18F-MK-6240 was shown to predict cognitive decline in cognitively unimpaired older adults.

Figure 5. Scatterplot diagrams illustrating the relationship between tau PET

Figure 5. Scatterplot diagrams illustrating the relationship between tau PET [ 18F-MK-6240] and processing speed change across brain regions. (A–D) The associations considering regional tau uptakes (meta-ROIs). (E) A forest plot representing the unstandardized betas and 95% interval confidence for each linear regression considering different 36 brain areas. The results highlighted (*) are not corrected for multiple comparisons. All regressions accounted for age at follow-up, sex/ gender, education, and baseline memory performance. Abbreviations: C/P, cingulate/parietal lobe; LTL, lateral temporal lobe; MTL, medial temporal lobe; ROI, region of interest; SUVR, standardized uptake value ratio.

Using data from the ongoing, longitudinal Reference Ability Neural Network Study, we evaluated the association of late-life tau deposition with retrospective cognitive change considering cognitive domains well established to decline with aging: episodic memory, speed processing, and reasoning. For tau quantification, a set of regions of interest (ROIs) was selected a priori: (1) total-ROI comprising selected areas, (2) medial temporal lobe-ROI, (3) lateral temporal lobe-ROI and (4) cingulate/parietal lobe-ROI. Using a sample of 41 cognitively healthy older adults, we found that higher levels of 18F-MK-6240 in brain regions linked to Alzheimer's disease—namely, the medial temporal lobe, cingulate, and parietal regions—were associated with faster declines in episodic memory and processing speed, but not in reasoning ability. This association persisted even when adjusting for demographic variables (like age, sex, and education), baseline cognitive function, and amyloid-β levels. As recently reported in Neurobiology of Aging, our findings highlight the role of pathological tau in areas susceptible to early buildup in driving cognitive changes seen in Alzheimer's disease, even in older adults without cognitive impairments and who have low amyloid-β levels. Despite the small sample size of the present study, our findings suggest that memory and processing speed declines typically seen in normal aging may be partly due to tau accumulation, emphasizing the importance of exploring long-term relationships between tau buildup and cognitive abilities beyond memory.

Sharon Sanz Simon, PhD
Associate Research Scientist (in the Taub Institute and the Gertrude H. Sergievsky Center)
sss2278@cumc.columbia.edu

Yaakov Stern, PhD
Florence Irving Professor of Neuropsychology (in Neurology, Psychiatry, the Gertrude H. Sergievsky Center, and the Taub Institute)
ys11@cumc.columbia.edu

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The Effects of Insufficient Sleep and Adequate Sleep on Cognitive Function in Healthy Adults

Molly Zimmerman, PhD   Adam M. Brickman, PhD    Marie-Pierre St-Onge, PhD, CCSH, FAHA
Molly Zimmerman, PhD   Adam Brickman, PhD    Marie-Pierre St-Onge, PhD, CCSH, FAHA

Sleep is essential for maintaining overall health and plays a pivotal role in cognitive processes vital for day-to-day functioning and overall quality of life, such as attention, memory, language, and executive functioning. Despite the focus on the negative cognitive effects of sleep deprivation, there has been little investigation into the impact of sleep consistency or the continuous achievement of sufficient sleep. Conducting such studies could broaden our knowledge of overall sleep health and potentially highlight a crucial target for treatment aimed at enhancing well-being.

In the current study, led by Dr. Molly Zimmerman, Professor of Psychology at Fordham University, in collaboration with Dr. Marie-Pierre St-Onge, Director of the Center for Excellence for Sleep & Circadian Research at Columbia, we assessed the cognitive effects of both insufficient and adequate sleep in 65 healthy adults, using a randomized, experimental approach. Our study also considered the potential influence of practice effects, which are improvements in test performance due to familiarity with the tasks rather than genuine cognitive gains. Differentiating between changes in cognition due to sleep quality and those due to repeated exposure to tests is crucial for accurate interpretation of the impact of sleep on cognitive function. We hypothesized that periods of insufficient sleep would lead to poorer cognitive performance compared to periods of adequate sleep, beyond the improvements attributed to task familiarity.

Fig. 2. Differences in performance on the List Sorting Working Memory test from the NIH Toolbox across the four study visits.

Figure 2. Differences in performance on the List Sorting Working Memory test from the NIH Toolbox across the four study visits. The improved score from the baseline of the first condition (B1) to the baseline of the second condition (B2) indicates a practice effect. Following the adequate sleep condition, participants showed greater improvement than what would be expected with practice. However, following the insufficient sleep condition, participants did not improve as much as would be expected with practice; there were no statistical differences between B1 and performance following the insufficient sleep condition. Values plotted are means (SE) derived from the repeated measures analysis of variance models.

As recently reported in Sleep Health, we found that maintaining adequate sleep consistently led to improvements in cognitive function, specifically working memory and response inhibition, surpassing the improvements that typically come from practice alone. Conversely, when individuals experienced consistently insufficient sleep, their ability to improve on cognitive function tests through practice was diminished compared to their performance with adequate sleep. These results contribute to our understanding of how various aspects of sleep quality and duration (including both the lack of sufficient sleep and the continuous maintenance of adequate sleep patterns) affect cognitive abilities. The findings indicate that ensuring a stable, consistent sleep schedule of at least 7 hours per night can enhance working memory and response inhibition in healthy adults.

Adam Brickman, PhD
Professor of Neuropsychology (in Neurology, the Taub Institute, and the Gertrude H. Sergievsky Center)
amb2139@cumc.columbia.edu

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