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



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April 2024:

Rare Genetic Variation in Fibronectin 1 (FN1) Protects Against APOEε4 in Alzheimer's Disease

Cell Subtype-Specific Effects of Genetic Variation in the Alzheimer's Disease Brain

Osteopontin Drives Neuroinflammation and Cell Loss in MAPT-N279K Frontotemporal Dementia Patient Neurons

Childhood Engagement in Cognitively Stimulating Activities Moderates Relationships Between Brain Structure and Cognitive Function in Adulthood

March 2024:

Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study

The Matrix Receptor CD44 Is Present in Astrocytes throughout the Human Central Nervous System and Accumulates in Hypoxia and Seizures

Microglia Measured by TSPO PET are Associated with Alzheimer's Disease Pathology and Mediate key Steps in a Disease Progression Model

A Comparative Study of Structural Variant Calling in WGS from Alzheimer's Disease Families

February 2024:

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

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

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

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

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




Updated Safety Results From Phase 3 Lecanemab Study in Early Alzheimer's Disease

Lawrence S. Honig, MD, PhD
Lawrence S. Honig, MD, PhD

The development of FDA-approved disease modifying therapies for Alzheimer's disease (AD) has been a major achievement in neurotherapeutics over the past few years. AD, which is a disease that affects cognition and memory, is caused by excessive beta-amyloid protein in the brain, which is deposited in the form of neuritic plaques, and is associated with the development of neurofibrillary degeneration and neurodegeneration including synaptic and ultimately neuronal cell losses. The clinical effects of AD, with disorientation, amnesia, language and visuospatial problems, and behavioral and functional impairments, places an enormous burden on the 7 million Americans, and others throughout the world, who are affected, and on their families, as well on healthcare systems. The development of therapies that slow the progression of disease has changed neurological care for persons with dementia. The most-used therapy is lecanemab, which is a monoclonal antibody that is administered intravenously and binds with high affinity to soluble beta-amyloid in the form of protofibrils, which are more toxic to neurons than monomeric beta-amyloid or insoluble polymeric forms of beta-amyloid. The drug lecanemab (also known as BAN-2401) is approved for use in the US, China, and Japan, after phase 2 and phase 3 studies proved that it decreased cerebral beta-amyloid levels, resulting in the marked clearance of beta-amyloid deposits known as senile neuritic plaques, and showed clear clinical benefits.

In the late 2010’s, an 18-month, phase 2, dose-finding study of lecanemab, using a Bayesian adaptive design was conducted in 856 participants with mild cognitive impairment (MCI) due to AD and mild dementia due to AD dementia (collectively termed “early AD”). This study showed removal of cerebral amyloid as measured by PET scans, favorable changes in a variety of fluid biomarkers, and evidence of dose-dependent clinical benefits. In the phase 2 study, as in prior studies of anti-amyloid antibodies, there were also side effects, most notably the dose-dependent development of brain edema and brain hemorrhages, called amyloid-related imaging abnormalities (ARIA). Following the phase 2 study, a phase 3, randomized, double-blind, placebo-controlled trial (called Clarity AD) with an open-label extension (OLE) was performed. This study confirmed lecanemab clinical efficacy, with slowing of cognitive and functional decline by a variety of neuropsychological and functional outcome measures, to the extent of 26% to 37% over the 18-month trial period, and resulted in the FDA-approval of the drug, and subsequent approval by regulatory authorities in Japan and China. While overall the drug was well tolerated in these trials, lecanemab treatment was again accompanied by not only some manageable infusion reactions (with greater incidence than in placebo), but also with ARIA-E (ARIA with edema or effusion) and ARIA-H (ARIA marked by microhemorrhages, superficial siderosis, or very rarely macrohemorrhages greater than 1 cm in diameter). ARIA-E and ARIA-H appear to be related to cerebral amyloid angiopathy (CAA), which in turn is significantly related to APOE-ε4 allele dosage.

Figure 1. Timing of ARIA-E events

Figure 1. Timing of ARIA-E events (A) overall and (B) by APOE4 genotype for lecanemab in Core + OLE and placebo in Core.

Now published in Alzheimer’s Research & Therapy, this publication presents detailed safety information from the double-blind Core phase and the OLE of the phase 3 Clarity AD study in early Alzheimer's disease. The data shows the serious adverse events and deaths which occurred during the study, and also more detailed and updated data on the cerebral side effects of ARIA-E and ARIA-H, complementing previously published trial data from the phase 2 and phase 3 Core studies. The phase 3 trial included 1795 participants in the Core phase and 1612 in the Core + OLE phases, with lecanemab showing good tolerability. During the Core phase there was no increase in deaths with lecanemab (0.7% deaths on lecanemab versus 0.8% deaths on placebo), but some increase in serious adverse events (14% on lecanemab vs 11% on placebo). Overall, frequent adverse events more common in the lecanemab group included infusion reactions (24.5%), ARIA-H (16.0%), and ARIA-E (13.6%). ARIA-E and ARIA-H events were predominantly mild-to-moderate in radiological severity; only about one in four ARIA-E events were symptomatic. Major findings are that ARIA-E occurs mostly in the first 3-6 months of therapy, and is much more common in ApoE ε4 homozygotes (33%), than in heterozygotes (11%), or non-carriers (5%); it is usually asymptomatic, and typically resolves over 90 days. ARIA-H microhemorrhages that are “isolated”, which is to say not occurring in the context of ARIA-E, are not clearly increased in incidence in those who received lecanemab treatment (8.7%) compared to those who received placebo (7.7%). Lecanemab treatment did seem to be associated with increase in isolated ARIA-H superficial siderosis, and likely in the rare macrohemorrhages that occurred in less than 0.5% of lecanemab-treated patients. ARIA-H is markedly related to ApoE genotype, with a monotonic increase in microhemorrhages over time, regardless of drug treatment, but occurring much more so in APOE e4 homozygotes, than heterozygotes or non-carriers.

The safety information on lecanemab is important for discussing risks and benefits in patients considering anti-amyloid therapy with lecanemab, and for understanding the FDA-mandated monitoring procedures, including three brain MRI studies in the first seven months of treatment with this drug. As increased numbers of patients receive anti-amyloid therapies, it is most important to have a thorough understanding of the potential risks, and the procedures to mitigate these risks through monitoring by healthcare providers, patients, and caregivers ensuring optimal patient management and care.

Lawrence S. Honig, MD, PhD
Professor of Neurology (in the Gertrude H. Sergievsky Center and the Taub Institute)
lh456@cumc.columbia.edu

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The Broken Alzheimer's Disease Genome

Cláudio Gouveia Roque, PhD   Hemali Phatnani, PhD   
Cláudio Gouveia Roque, PhD    Hemali Phatnani, PhD    Ulrich Hengst, PhD

Genomics and related big data disciplines have revolutionized our understanding of Alzheimer’s disease. However, no single genomic modality, no matter how rich in detail, provides a complete picture of the disease on its own. From genetics to proteomics, all biological layers contribute interconnected pieces of evidence.

Graphical Abstract

Figure. Graphical Abstract

In "The Broken Alzheimer’s Disease Genome," we explore this complementarity and offer a comprehensive overview of how genomic research has advanced our thinking of late-onset Alzheimer’s beyond the classical pathology hallmarks. Our review, now published in Cell Genomics, facilitates an integrated discussion of recent genetic, epigenetic, transcriptomic, and proteomic findings. This broad framing is used deliberately: by thinking holistically rather than narrowly about specific processes, we strived to promote dialogue across subfields. Our emphasis on the synergies among data modalities results in a unique and rich perspective that substantially expands upon prior systematization efforts. We further discuss clinical applications, such as risk prediction tools and biomarkers, and outline how genomics is shaping drug development.

Cláudio Gouveia Roque, PhD
New York Genome Center
croque@nygenome.org

Hemali Phatnani, PhD
Assistant Professor of Neurological Sciences (in Neurology)
hp2286@cumc.columbia.edu

Ulrich Hengst, PhD
Professor of Pathology and Cell Biology (in the Taub Insitute)
uh2112@cumc.columbia.edu

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Personality Traits and Cognitive Reserve—High Openness Benefits Cognition in the Presence of Age-Related Brain Changes

Annabell Coors, PhD    Yaakov Stern, PhD
Annabell Coors, PhD    Yaakov Stern, PhD

It is known that some people are less susceptible to age-related pathological changes in the brain and therefore perform better on cognitive tasks than would be expected given their brain (health) status. These individuals are said to have higher cognitive reserve (CR). It is important to gain a deeper understanding of what sets them apart. We can use this knowledge to learn how to age healthier and to identify individuals who are at increased risk of cognitive decline and need targeted interventions. We hypothesized that personality influences leisure behavior and may therefore be linked to the level of CR.

Personality and Cognitive Domain Scores.

Figure 2. Personality and Cognitive Domain Scores. This forest plot shows how much performance in different cognitive domains (see y-axis) differs per one SD increase in each of the BIG 5 personality dimensions. Associations were adjusted for the cognitive domain-specific brain status variable, age, and sex. Each dot represents the standardized estimate for the association, while the lines around it show the 95%-confidence interval belonging to this estimate. The corresponding values are shown in the column on the right side with significant associations printed in bold. Notably, all dots on the right side of the dotted vertical line indicate that higher values in the respective personality dimension are associated with better cognitive performance in the specific domain, while all dots on the left side indicate that higher values in the respective personality dimension were associated with lower cognitive performance.

Thus, we measured the personality traits openness, conscientiousness, extraversion, agreeableness, and neuroticism with a questionnaire and examined whether they underlie CR throughout adulthood. Leveraging both cross-sectional (N=399) and longitudinal (N=273) data, we assessed the cognitive abilities of healthy individuals between 19 to 80 years old across different cognitive domains (perceptual speed, memory, fluid reasoning, vocabulary). To quantify brain status, we used MRI-derived cortical thickness and volume variables of brain regions associated with cognitive performance.

As recently reported in the journal Neurobiology of Aging, our findings suggest that individuals with higher levels of openness tend to have superior fluid reasoning abilities and vocabulary, even after adjusting for brain status, age, and sex. Moreover, a worse brain status at baseline assessment was associated with decline in perceptual speed only in individuals with lower levels of openness. In individuals with high openness, brain status at baseline was not related to change in perceptual speed. This suggests that high openness - a personality trait characterized by creativity, imagination, and interests in new things - underlies higher CR. Contrary to our expectations, high neuroticism (low emotional stability) did not underlie lower CR. We believe that some previous studies found this association because their study samples included individuals who already had or were on the verge of developing Alzheimer’s disease. Alzheimer’s disease could be a common underlying cause of both high neuroticism and low CR, rather than high neuroticism and low CR being directly related.

The key message of our research project is that it is beneficial to be and remain open to experience, as high openness helps to counteract the negative effects of age-related brain pathology on cognition. Importantly, a person’s personality is not set in stone and can change, especially in response to major life changes such as marriage, divorce, or unemployment. Unfortunately, many people show a decline in openness in older age, which may be due to reduced exposure to new and challenging contexts. For them, engagement in volunteer work or training in new skills and competencies could foster high levels of openness and protect against cognitive decline.

Annabell Coors, PhD
Postdoctoral Research Scientist in the Taub Institute
ac5256@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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