Visual Impairment
Visual impairment refers to any decrease in vision that causes problems not correctable by standard means like corrective lenses, ranging from partial sight loss to complete blindness. This condition can significantly impact an individual’s ability to perform daily activities, such as reading, navigating environments, and recognizing faces, thereby affecting their overall quality of life.
The biological basis of visual impairment is complex and multifaceted, involving intricate processes within the eyes, optic nerves, and the brain’s visual processing centers. Genetic factors play a substantial role in the predisposition and development of many forms of visual impairment. For instance, specific genetic variations, including those in early complement genes, have been linked to visual system degeneration, as observed in conditions like multiple sclerosis[1]. Furthermore, research explores the genomic influences on visual cognition, highlighting the broad genetic underpinnings of visual functions [2]. The genetic architecture can vary from single-gene disorders, where a mutation in one gene causes the condition, to polygenic traits, where multiple genes contribute to the risk or severity.
From a clinical perspective, understanding the genetic and biological mechanisms of visual impairment is crucial for early diagnosis, personalized intervention strategies, and the potential prevention of further vision loss. Early detection can enable timely access to treatments, assistive devices, and rehabilitation services. Beyond the individual clinical impact, visual impairment presents significant social challenges. Affected individuals may encounter barriers in educational attainment, employment opportunities, and full participation in society due to accessibility issues. Consequently, there is a strong social importance in developing supportive policies, advancing assistive technologies, and fostering inclusive environments to empower individuals with visual impairment and enhance their independence and quality of life.
Limitations
Section titled “Limitations”Understanding the genetic and biological underpinnings of visual impairment is subject to several methodological and interpretative limitations that warrant careful consideration. These limitations affect the robustness, generalizability, and completeness of current knowledge in the field.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Genetic studies often face challenges related to sample size, which can limit their statistical power to detect associations, especially for traits influenced by numerous genetic variants with small individual effects[2]. Such limitations can lead to suggestive findings that require replication in much larger cohorts to confirm their validity and prevent the overestimation of effect sizes [2]. The potential for effect-size inflation is particularly relevant in meta-analyses that may not fully account for heterogeneity across different study populations[3].
Furthermore, biases in study design, such as an imbalance in the representation of sexes within cohorts, can introduce confounding factors that impact genetic associations [2]. An uneven gender distribution might obscure or misinterpret sex-specific genetic influences on visual traits, underscoring the necessity for more balanced participant recruitment in future research to enhance the applicability of findings [2]. These methodological constraints collectively influence the reliability and broad utility of identified genetic loci.
Phenotypic Definition and Generalizability
Section titled “Phenotypic Definition and Generalizability”The generalizability of genetic findings for visual traits, including impairment, is often constrained by the demographic characteristics of study populations, which frequently consist predominantly of specific ancestries [2]. This limited diversity can impede the transferability of identified genetic risk factors to other populations, where genetic architectures or environmental interactions may differ significantly [4]. Future research efforts should prioritize the inclusion of more diverse cohorts to ensure that genetic insights are broadly applicable across global populations.
Accurate and consistent phenotyping is crucial for robust genetic association studies, yet variations in how visual traits are measured can substantially influence results [2]. For example, studies on visual perception may not consistently record or categorize complex perceptual states, or may use response protocols that diverge from established methodologies, potentially affecting heritability and association outcomes [2]. Critically, much of the research in this area has focused on visual cognition in individuals with normal or corrected-to-normal visual acuity, which, while valuable for understanding fundamental visual processing, may not directly provide insights into the genetic underpinnings ofvisual impairment itself [2].
Incomplete Genetic Architecture
Section titled “Incomplete Genetic Architecture”The complete genetic architecture of complex visual traits, including visual impairment, remains challenging to fully elucidate. This is partly due to the phenomenon of “missing heritability,” where common genetic variants explain only a fraction of the total phenotypic variation, and difficulties in accurately estimating SNP heritability[2]. This suggests that current genetic models may not fully capture the intricate interplay of genetic factors, including those with smaller effects or less common alleles, contributing to the trait [5].
Further knowledge gaps persist in thoroughly understanding the contributions of rare variants, structural genetic variations, and complex gene-environment interactions, which are often not comprehensively addressed in current genomic analyses. While studies indicate that genetic associations are enriched in gene regulatory regions, the precise mechanisms through which these non-coding variants influence visual function and impairment are still being uncovered [6]. Bridging these gaps necessitates more comprehensive multi-omic approaches and longitudinal studies capable of capturing the dynamic interplay between genetic predispositions and environmental influences throughout an individual’s lifespan.
Variants
Section titled “Variants”Genetic variations in genes such as CFH, ARMS2, TCF7L2, and STK19are associated with various physiological processes that can impact visual health and related conditions. These single nucleotide polymorphisms (SNPs) can alter gene function or expression, contributing to the risk of complex diseases. Genome-wide association studies (GWAS) have been crucial in identifying many such genetic loci across diverse populations[7].
Variants within the CFH (Complement Factor H) and ARMS2(Age-Related Maculopathy Susceptibility 2) genes are particularly notable for their strong association with Age-related Macular Degeneration (AMD), a leading cause of vision loss.CFH encodes a protein that regulates the complement system, a crucial part of the innate immune response. The rs579745 variant in CFHmay influence the efficiency of this regulation, and dysregulation of the complement system is implicated in chronic inflammation that can damage retinal cells. Indeed, early complement genes have been linked to visual system degeneration in conditions like multiple sclerosis[1]. Similarly, the rs36212732 variant in ARMS2 is a major genetic risk factor for AMD, though the precise mechanism by which ARMS2influences retinal health is still under investigation. Both genes contribute significantly to the genetic predisposition for AMD, highlighting the complex interplay of immune regulation and retinal cell function in maintaining visual acuity[8].
The TCF7L2(Transcription Factor 7 Like 2) gene is widely recognized for its strong association with type 2 diabetes. TCF7L2 plays a vital role in the Wnt signaling pathway, which is essential for cell development and metabolism, particularly in regulating insulin secretion and glucose homeostasis. Variants likers7903146 and rs34872471 in TCF7L2are linked to an increased risk of developing type 2 diabetes by affecting pancreatic beta-cell function. Although not directly involved in primary visual impairment, the strong link betweenTCF7L2variants and diabetes carries significant implications for visual health, as diabetic retinopathy is a major complication of diabetes and a leading cause of blindness worldwide[9].
Another gene, STK19(Serine/Threonine Kinase 19), encodes a kinase involved in cellular signaling pathways. While the specific functions of STK19 are still being fully elucidated, kinases are critical enzymes that regulate a vast array of cellular processes, including cell growth, metabolism, and immune responses. Thers387608 variant in STK19may influence the protein’s activity or expression, potentially impacting these fundamental cellular functions. Genetic variations in such ubiquitous regulatory genes can contribute to the overall susceptibility to complex traits, including those that might indirectly affect the integrity and function of the visual system or contribute to other age-related conditions[10].
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs579745 | CFH | degeneration of macula and posterior pole macular degeneration retinopathy visual impairment |
| rs36212732 | ARMS2 | refractive error age-related macular degeneration drug use measurement, macular degeneration visual impairment macular degeneration |
| rs7903146 rs34872471 | TCF7L2 | insulin measurement clinical laboratory measurement, glucose measurement body mass index type 2 diabetes mellitus type 2 diabetes mellitus, metabolic syndrome |
| rs387608 | STK19 | blood protein amount C3a anaphylatoxin des arginine measurement gp41 C34 peptide, HIV measurement rap guanine nucleotide exchange factor 5 measurement ras-related protein Rab-35 measurement |
Defining Visual Impairment and Related Terminology
Section titled “Defining Visual Impairment and Related Terminology”Visual impairment encompasses a spectrum of conditions affecting an individual’s sight, which are broadly referred to as “vision disorders”[2]. A key benchmark in assessing visual status is “visual acuity,” which measures the sharpness of vision and the eye’s ability to discern fine details[2]. The concept of “normal or corrected-to-normal visual acuity” serves as an important operational definition, indicating that an individual’s vision, either naturally or with the aid of corrective lenses, meets standard criteria for unimpaired sight[2]. In research settings, participants are often screened to ensure they have “normal or corrected-to-normal visual acuity,” thereby excluding individuals with pre-existing vision disorders to maintain cohort homogeneity for specific study objectives[2].
Measurement and Diagnostic Approaches for Visual Acuity
Section titled “Measurement and Diagnostic Approaches for Visual Acuity”The precise measurement of visual acuity is fundamental to the diagnosis and classification of visual impairment. One common approach involves specialized software programs like FrACT v3.8.2, which is based on the Freiburg Vision Test[2]. This test employs a Landolt-C optotype, a standardized ring with a gap, presented at a set distance, requiring subjects to identify the orientation of the gap from multiple choices [2]. The software then calculates the individual’s acuity threshold using a method known as “Best Parameter Estimation by Sequential Testing” [2]. Such standardized clinical and research criteria are essential for objectively quantifying visual function and distinguishing between typical vision and various degrees of vision disorders [2].
Causes
Section titled “Causes”Visual impairment is a complex condition influenced by a myriad of factors, including genetic predispositions, age-related physiological changes, co-occurring health conditions, and environmental interactions. Understanding these diverse causal pathways is crucial for comprehensive management and prevention.
Genetic Predisposition and Molecular Pathways
Section titled “Genetic Predisposition and Molecular Pathways”Visual impairment, like many complex traits, often stems from a combination of genetic factors, ranging from single gene disorders to polygenic influences. Research indicates that specific genetic variants, such as “early complement genes,” are associated with “visual system degeneration” in conditions like multiple sclerosis, highlighting the role of immune-related pathways in visual health[1]. The overall genetic architecture of such complex traits is frequently “highly polygenic,” meaning numerous common genetic variants, each with a small effect, collectively contribute to an individual’s susceptibility [5]. Furthermore, “genomic analyses of visual cognition” suggest that genetic factors broadly influence visual processing, indicating that inherited predispositions can impact various aspects of visual function and vulnerability to impairment [2].
Age-Related Changes and Comorbidities
Section titled “Age-Related Changes and Comorbidities”The development and progression of visual impairment are significantly influenced by age and the presence of co-occurring health conditions. Degenerative processes leading to “visual system degeneration” can be exacerbated by increasing “age” and the “disease duration” of underlying conditions, such as multiple sclerosis[1]. In these scenarios, visual impairment emerges not just from primary ocular issues but as a secondary effect or comorbidity of a broader systemic disease. The interplay of genetic predispositions with the aging process and disease progression collectively shapes the trajectory of visual health.
Environmental Modulators and Gene-Environment Interactions
Section titled “Environmental Modulators and Gene-Environment Interactions”Environmental factors and their interactions with an individual’s genetic makeup can modulate the risk and severity of visual impairment. While specific environmental triggers for visual impairment are not detailed in the provided studies, analyses often account for “genetic ancestry” when studying disease associations, which can implicitly reflect population-specific environmental exposures or lifestyle patterns[1]. This suggests that an individual’s inherited genetic background may interact with external factors, influencing susceptibility or resilience to visual conditions. Such gene-environment interactions contribute to the observed variability in visual impairment prevalence and severity across different populations.
Biological Background
Section titled “Biological Background”Visual impairment encompasses a range of conditions that affect an individual’s ability to see, stemming from complex biological mechanisms impacting the eye, optic nerve, and brain. Understanding the biological underpinnings involves exploring genetic predispositions, cellular pathologies, and the intricate neural networks responsible for visual processing. These factors can lead to diverse forms of visual dysfunction, from direct damage to ocular structures to disruptions in how the brain interprets visual information.
Genetic Basis and Regulation of Visual Health
Section titled “Genetic Basis and Regulation of Visual Health”The integrity and function of the visual system are significantly influenced by an individual’s genetic makeup. Research indicates that early complement genes are associated with degeneration within the visual system, particularly in conditions like multiple sclerosis[1]. These genes are crucial for the immune response, suggesting that their dysregulation can directly contribute to the pathological processes that lead to visual impairment[1]. Furthermore, genomic analyses, including genome-wide association studies (GWAS), are instrumental in dissecting the genetic architecture of complex visual traits and visual cognition [2]. Such studies aim to identify specific gene functions and regulatory elements that govern fundamental visual abilities, such as visual acuity, and influence perceptual experiences like binocular rivalry[2].
Cellular and Molecular Pathophysiology of Visual Impairment
Section titled “Cellular and Molecular Pathophysiology of Visual Impairment”Visual impairment often originates from disruptions at the cellular and molecular levels, which can profoundly affect the delicate structures of the visual system. A critical pathophysiological process observed in conditions like optic neuritis is retinal nerve fiber layer axonal loss, a direct cause of visual dysfunction[1]. This cellular damage can be driven by aberrant signaling pathways, potentially involving immune system components regulated by early complement genes, leading to a disturbance in cellular homeostasis and progressive degeneration [1]. Understanding these intricate molecular mechanisms is essential for elucidating the etiology of various forms of visual impairment and for developing targeted interventions.
Organ-Level Effects and Visual System Degeneration
Section titled “Organ-Level Effects and Visual System Degeneration”At the organ level, visual impairment is characterized by specific effects on the eye and its neural connections, leading to a decline in overall visual function. Degeneration of the visual system, notably involving the optic nerve and retina, results in compromised signal transmission from the eye to the brain, which is fundamental for sight[1]. The integrity of the retinal nerve fiber layer is particularly vital, as its health directly correlates with visual acuity and the ability to perceive visual details[1]. These tissue interactions highlight how localized damage within the visual pathway can have widespread consequences for an individual’s ability to process and interpret their visual environment.
Neurological Basis of Visual Cognition
Section titled “Neurological Basis of Visual Cognition”Beyond direct structural damage, visual impairment can also encompass deficits in visual cognition, which involves the complex processing of visual information within the brain. This includes phenomena such as perceptual rivalry, where the brain alternates between different interpretations of ambiguous visual input, and top-down control mechanisms that modulate visual attention and interpretation[2]. The biological mechanisms underlying these cognitive aspects of vision are explored through genomic analyses, revealing how genetic variations can impact the neural circuits responsible for integrating visual stimuli into coherent perceptions [2]. Understanding these intricate brain-level processes is crucial for addressing impairments that affect not just what is seen, but how it is understood.
Neural Signaling and Visual Processing Networks
Section titled “Neural Signaling and Visual Processing Networks”Visual impairment often stems from disruptions in the intricate neural signaling pathways responsible for capturing and interpreting light. This process begins with receptor activation in photoreceptor cells, where light energy is transduced into electrochemical signals via highly specialized G-protein coupled receptor cascades[2]. These initial signals then propagate through complex intracellular signaling cascades, involving various kinases and second messengers, which ultimately regulate gene expression through transcription factor activation, ensuring the continuous adaptation and function of visual neurons. The dynamic interplay of these signaling events, including crucial feedback loops, is essential for sharpening visual acuity and maintaining the fidelity of visual information transmission from the retina to the brain.
Beyond initial light perception, visual impairment can also involve higher-level processing networks within the brain. Visual cognition, encompassing aspects like perceptual rivalry and top-down control, relies on the sophisticated integration of signals across multiple brain regions[2]. This systems-level integration involves extensive pathway crosstalk and network interactions, where different neural circuits communicate and coordinate to construct a coherent visual experience. Hierarchical regulation ensures that visual information is progressively analyzed and interpreted, with emergent properties arising from the collective activity of these interconnected networks, allowing for complex visual tasks and object recognition.
Genetic and Epigenetic Regulatory Mechanisms
Section titled “Genetic and Epigenetic Regulatory Mechanisms”The development, maintenance, and susceptibility to degeneration of the visual system are profoundly influenced by genetic and epigenetic regulatory mechanisms. Gene regulation, controlled by specific transcription factors, dictates the precise expression of genes critical for the formation of photoreceptors, retinal ganglion cells, and optic nerve integrity. Genetic variations, identified through genome-wide association studies across various neurological impairments, can alter these fundamental regulatory pathways, influencing protein synthesis and function within the visual system [11]. Such alterations can lead to structural defects or functional deficiencies that predispose individuals to visual impairment.
Furthermore, post-translational regulation, including protein modification such as phosphorylation, ubiquitination, or glycosylation, plays a crucial role in fine-tuning the activity, localization, and stability of proteins essential for visual function. These modifications can act as molecular switches, rapidly activating or deactivating proteins involved in signaling cascades, synaptic transmission, and cellular maintenance. Disruptions in these regulatory mechanisms can lead to the accumulation of misfolded or dysfunctional proteins, impairing cellular homeostasis and contributing to the pathogenesis of various forms of visual degeneration.
Metabolic Homeostasis and Cellular Resilience
Section titled “Metabolic Homeostasis and Cellular Resilience”Maintaining metabolic homeostasis is critical for the highly energy-demanding cells of the visual system, particularly photoreceptors and neurons in the visual cortex. Efficient energy metabolism, primarily through ATP production, is indispensable for processes such as photoreceptor outer segment renewal, neurotransmitter synthesis, and the maintenance of ion gradients necessary for electrical signaling. Concurrently, robust biosynthesis pathways are required for the continuous production of essential components, including lipids for cell membranes and photopigments for light absorption, ensuring the structural and functional integrity of ocular tissues.
Dysregulation in catabolism, metabolic regulation, and flux control can significantly compromise cellular resilience within the visual system. Imbalances in these pathways can lead to oxidative stress, accumulation of toxic byproducts, or insufficient energy supply, all of which can damage delicate visual cells. While research on systemic metabolic markers, such as plasma lipids, has been linked to other forms of neurodegeneration, their direct impact on visual impairment underscores the broader principle that metabolic health is intertwined with neuronal viability and function[12]. Therefore, maintaining precise metabolic control is vital for protecting against cellular damage and preserving long-term visual acuity.
Immune-Mediated Degeneration and Pathway Dysregulation
Section titled “Immune-Mediated Degeneration and Pathway Dysregulation”Immune-mediated mechanisms represent a significant pathway contributing to visual system degeneration, particularly in neuroinflammatory conditions. The involvement of early complement genes has been specifically associated with visual system degeneration in diseases such as multiple sclerosis[1]. This indicates that an overactive or dysregulated immune response, involving components of the innate immune system, can directly contribute to neuronal damage and loss within the optic nerve and retina.
Such pathway dysregulation often initiates inflammatory cascades that disrupt the delicate microenvironment of the visual system, leading to cellular stress and progressive tissue damage. These inflammatory processes can interfere with signaling pathways, impair metabolic functions, and compromise the structural integrity of neurons and glial cells. Understanding these disease-relevant mechanisms, including any compensatory mechanisms the body employs, is crucial for identifying potential therapeutic targets aimed at modulating immune responses and mitigating neurodegeneration to preserve visual function[1]. The presence of genetic modifiers of disease risk further highlights the complex interplay between genetic predisposition and immune system pathways in determining the onset and progression of visual impairment[11].
Frequently Asked Questions About Visual Impairment
Section titled “Frequently Asked Questions About Visual Impairment”These questions address the most important and specific aspects of visual impairment based on current genetic research.
1. If my parents have vision problems, will I definitely get them too?
Section titled “1. If my parents have vision problems, will I definitely get them too?”Not necessarily. While genetic factors play a substantial role in the predisposition and development of many forms of visual impairment, it’s not always a direct inheritance. Some conditions are single-gene disorders, but many are polygenic, meaning multiple genes contribute, and the severity can vary greatly.
2. Could my vision problems start really young because of my genes?
Section titled “2. Could my vision problems start really young because of my genes?”Yes, genetic factors can indeed predispose individuals to visual impairment from an early age. Understanding the genetic basis is crucial for early diagnosis, which can lead to timely access to treatments, assistive devices, and rehabilitation services, potentially preventing further vision loss.
3. Why did my vision get worse so fast compared to my friend’s, even with similar issues?
Section titled “3. Why did my vision get worse so fast compared to my friend’s, even with similar issues?”Differences in how quickly vision deteriorates can be influenced by your unique genetic architecture. Visual impairment can be a polygenic trait, where various genes contribute to the risk or severity, explaining why progression can vary significantly between individuals.
4. Can knowing my genetic risks help doctors treat my specific vision issues better?
Section titled “4. Can knowing my genetic risks help doctors treat my specific vision issues better?”Absolutely. Understanding the genetic and biological mechanisms of your visual impairment is crucial for personalized intervention strategies. This knowledge allows for more targeted treatments and can help in the potential prevention of further vision loss tailored specifically to your genetic profile.
5. Does my genetic makeup make it harder for me to do everyday things like read or recognize faces?
Section titled “5. Does my genetic makeup make it harder for me to do everyday things like read or recognize faces?”Yes, genetic factors can significantly influence visual functions, making it harder to perform daily activities. Research explores the genomic influences on visual cognition, indicating that your genes can broadly underpin how well your visual system processes information needed for tasks like reading and recognizing faces.
6. Can my lifestyle choices actually overcome my family’s history of vision problems?
Section titled “6. Can my lifestyle choices actually overcome my family’s history of vision problems?”While genetics play a significant role, the exact interplay between your genes and environmental factors, including lifestyle, is complex and still being fully understood. While specific gene-environment interactions are knowledge gaps, lifestyle choices can sometimes influence the expression or progression of genetically predisposed conditions.
7. Does my family’s ethnic background affect my risk for certain vision problems?
Section titled “7. Does my family’s ethnic background affect my risk for certain vision problems?”Yes, your ancestry can matter. Genetic findings for visual traits are often studied in populations of specific ancestries, and these findings may not apply universally. Different populations can have unique genetic architectures or environmental interactions that influence visual impairment risk.
8. My sibling has perfect vision, but I struggle with mine. Why the difference?
Section titled “8. My sibling has perfect vision, but I struggle with mine. Why the difference?”Even within the same family, genetic predispositions can manifest differently. Visual impairment can be influenced by a complex interplay of many genes (polygenic traits), where you and your sibling might have inherited different combinations of genetic variants that affect your individual risk and vision development.
9. Does getting a genetic test help me plan for my future with vision issues?
Section titled “9. Does getting a genetic test help me plan for my future with vision issues?”Yes, genetic insights are valuable for future planning. Early diagnosis through understanding your genetic predispositions can lead to personalized intervention strategies and a better understanding of potential progression. This allows for proactive measures and access to supportive resources.
10. Could my other health conditions, like multiple sclerosis, be linked to my vision problems genetically?
Section titled “10. Could my other health conditions, like multiple sclerosis, be linked to my vision problems genetically?”Yes, there can be genetic links between other health conditions and visual impairment. For example, specific genetic variations, such as those in early complement genes, have been associated with visual system degeneration observed in conditions like multiple sclerosis.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Fitzgerald KC et al. “Early complement genes are associated with visual system degeneration in multiple sclerosis.”Brain, 2019, PMID: 31289819.
[2] Chen B et al. “Genomic analyses of visual cognition: perceptual rivalry and top-down control.” J Neurosci, 2018, PMID: 30242048.
[3] St Pourcain, B. et al. “Common variation contributes to the genetic architecture of social communication traits.” Mol Autism, 2013.
[4] Jia, P. et al. “Genome-wide association study of HIV-associated neurocognitive disorder (HAND): A CHARTER group study.” Am J Med Genet B Neuropsychiatr Genet, 2017.
[5] Fransen E et al. “Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment.”Eur J Hum Genet, 2015, PMID: 24939585.
[6] Kalra, G. et al. “Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty.” PLoS Genet, 2020.
[7] Hoffmann TJ et al. “A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.”PLoS Genet, 2016.
[8] Nagtegaal AP et al. “Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment.”Sci Rep, 2019.
[9] Wells HRR et al. “GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank.” Am J Hum Genet, 2019.
[10] Bakken, TE et al. “Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.” Proc Natl Acad Sci U S A, 2012.
[11] Pottier, C., et al. “Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.”Lancet Neurol, 2018, PMID: 29724592.
[12] Lutz, M. W., et al. “Analysis of pleiotropic genetic effects on cognitive impairment, systemic inflammation, and plasma lipids in the Health and Retirement Study.”Neurobiol Aging, 2019, PMID: 31201950.