Could differential under-reporting of loneliness between men and women bias the gender-specific association between loneliness duration and rate of memory decline? A probabilistic bias analysis of effect modification.

Gender is an observed effect modifier of the association between loneliness and memory aging. However, this effect modification may be a result of information bias due to differential loneliness under-reporting by gender. We applied probabilistic bias analyses to examine whether effect modification of the loneliness-memory decline relationship by gender is retained under three simulation scenarios with various magnitudes of differential loneliness under-reporting between men and women. Data were from biennial interviews with adults aged 50+ in the US Health and Retirement Study from 1996-2016 (5,646 women and 3,386 men). Loneliness status (yes vs. no) was measured from 1996-2004 using the CES-D loneliness item and memory was measured from 2004-2016. Simulated sensitivity and specificity of the loneliness measure were informed by a validation study using the UCLA Loneliness Scale as a gold standard. The likelihood of observing effect modification by gender was higher than 90% in all simulations, although the likelihood reduced with an increasing difference in magnitude of the loneliness under-reporting between men and women. The gender difference in loneliness under-reporting did not meaningfully affect the observed effect modification by gender in our simulations. Our simulation approach may be promising to quantify potential information bias in effect modification analyses.

Occupation, Retirement Age, and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study.

INTRODUCTION: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. METHODS: Current or most recent occupation at ARIC baseline (1987-89; ages 45-64y) was categorized based on 1980 US census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n=14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999-2007 was classified as occurring before or after age 70 (n=7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990-92) to visit 5 (2011-2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. RESULTS: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in White women but slower decline in Black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in White men and women and in Black men. Results did not change substantially after accounting for attrition. CONCLUSION: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in White participants and in Black men. Further research should explore reasons for the observed associations and race-sex differences.

Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial).

OBJECTIVES: To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia. METHODS: The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist. RESULTS: The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6-month follow-up, with a difference in change between MPH and placebo of 2.8 lb (95% confidence interval, CI: 0.7, 4.9 lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow-up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post-baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period. CONCLUSIONS: MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.

Does education moderate gender disparities in later-life memory function? A cross-national comparison of harmonized cognitive assessment protocols in the United States and India.

INTRODUCTION: We compared gender disparities in later-life memory, overall and by education, in India and the United States (US). METHODS: Data (N = 7443) were from harmonized cognitive assessment protocols (HCAPs) in the Longitudinal Aging Study of India-Diagnostic Assessment of Dementia (LASI-DAD; N = 4096; 2017-19) and US Health and Retirement Study HCAP (HRS-HCAP; N = 3347; 2016-17). We derived harmonized memory factors from each study using confirmatory factor analysis. We used multivariable-adjusted linear regression to compare gender disparities in memory function between countries, overall and by education. RESULTS: In the United States, older women had better memory than older men (0.28 SD-unit difference; 95% CI: 0.22, 0.35). In India, older women had worse memory than older men (-0.15 SD-unit difference; 95% CI: -0.20, -0.10), which attenuated with increasing education and literacy. CONCLUSION: We observed gender disparities in memory in India that were not present in the United States, and which dissipated with education and literacy.

Cross-national comparisons of later-life cognitive function using data from the Harmonized Cognitive Assessment Protocol (HCAP): Considerations and recommended best practices.

The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross-national comparisons of risk factor associations using HCAP data. Because existing and planned HCAP studies provide cognition data representing an estimated 75% of the global population ≥65 years of age, these recommended best practices will support high-quality comparative analyses of cognitive aging around the world. The principles described in this perspective are applicable to any researcher aiming to integrate or compare harmonized data on cognitive outcomes and their risk and protective factors across diverse populations.

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

BACKGROUND: We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). METHODS: Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses. RESULTS: APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (ßε4×age = -0.44, p = 0.03), orientation (ßε4×age = -0.07, p = 0.01), and language/fluency (ßε4×age = -0.07, p = 0.01), as well as in females for memory (ßε4×male = 0.17, p = 0.02) and language/fluency (ßε4×male = 0.12, p = 0.03). DISCUSSION: APOE Îµ4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals. HIGHLIGHTS: APOE Îµ4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education.

Considerations for the use of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in cross-country comparisons of cognitive aging and dementia.

INTRODUCTION: Informant reports are a critical component of dementia diagnoses, but the comparability of informant reports across countries is not well understood. METHODS: We compared the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) using population-representative surveys in the United States (N = 3183), England (N = 1050), and India (N = 4047). RESULTS: Analyses of regression splines and comparisons of model fit showed strong associations between IQCODE and objective cognition at low cognitive functioning in the United States and England; in India, the association was weaker but consistent over the range of cognition. Associations between IQCODE score and informant generation (analysis of variance [ANOVA] p = 0.001), caregiver status (p < 0.001), and years known by the informant (p = 0.015) were different across countries after adjusting for objective cognition. DISCUSSION: In India, the IQCODE was less sensitive to impairments at the lowest levels of cognitive functioning. Country-specific adjustments to IQCODE scoring based on informant characteristics may improve cross-national comparisons. HIGHLIGHTS: Associations between IQCODE and cognitive testing were similar in the United States and England but differed in India. In India, the IQCODE may be less sensitive to impairments among those with low cognition and no education. Informant characteristics may differentially impact informant reports of decline across countries. Adjustments or culturally sensitive adaptations may improve cross-national comparability.

Lifetime occupational skill and later-life cognitive function among older adults in the United States, Mexico, India, and South Africa.

INTRODUCTION: We conducted a cross-national comparison of the association between main lifetime occupational skills and later-life cognitive function across four economically and socially distinct countries. METHODS: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women. RESULTS: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa. DISCUSSION: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association. HIGHLIGHTS: No studies have examined cross-national differences in the association of occupational skill with cognition. We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa. The association of occupational skill with cognitive function varies by country and gender.

Patterns of cognitive domain abnormalities enhance discrimination of dementia risk prediction: The ARIC study.

INTRODUCTION: The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated. METHODS: We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models. RESULTS: Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk). DISCUSSION: By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression. HIGHLIGHTS: Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.

Sensory and motor deficits as contributors to early cognitive impairment.

INTRODUCTION: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI). METHODS: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function. RESULTS: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%). DISCUSSION: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI. HIGHLIGHTS: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI.

Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV.

Cognitive disorders are prevalent in people with HIV (PWH) despite antiretroviral therapy. Given the heterogeneity of cognitive disorders in PWH in the current era and evidence that these disorders have different etiologies and risk factors, scientific rationale is growing for using data-driven models to identify biologically defined subtypes (biotypes) of these disorders. Here, we discuss the state of science using machine learning to understand cognitive phenotypes in PWH and their associated comorbidities, biological mechanisms, and risk factors. We also discuss methods, example applications, challenges, and what will be required from the field to successfully incorporate machine learning in research on cognitive disorders in PWH. These topics were discussed at the National Institute of Mental Health meeting on "Biotypes of CNS Complications in People Living with HIV" held in October 2021. These ongoing research initiatives seek to explain the heterogeneity of cognitive phenotypes in PWH and their associated biological mechanisms to facilitate clinical management and tailored interventions.

Measurement of Prevalent Versus Incident Dementia Cases in Epidemiologic Studies.

Because dementia is progressive, incident cases are on average milder than prevalent cases, affecting the performance of cognitive tests and questions on functional limitations (i.e., cognition/functional limitation items) used for dementia assessment. Longitudinal studies assess incident cases, while cross-sectional studies assess prevalent cases, but differences are not typically considered when researchers select items to include in studies. We used longitudinal data from the Religious Orders Study and Memory and Aging Project (ROSMAP) (n = 3,446) collected between 1994 and 2021 to characterize differences in associations between items (cognition: 35 items; functional limitations: 14 items) and incident or prevalent dementia using multinomial regression models with generalized estimating equations, controlling for ROSMAP cohort (Religious Orders Study or Memory and Aging Project), age, sex, race, and education. The association between a given item and incident dementia was significantly weaker than the association between the same item and prevalent dementia for 46 of 49 items. However, there was variability, with larger differences for some items, including naming a pencil (prevalence odds ratio = 0.02 (95% confidence interval: 0.02, 0.03); incidence odds ratio = 0.10 (95% confidence interval: 0.06, 0.17); P for difference < 0.001). Important differences exist in the performance of cognition/functional limitation items for measurement of incident versus prevalent dementia. Differences can inform the choice of items for cross-sectional studies of prevalent cases or longitudinal studies of incident cases, leading to reduced misclassification and increased statistical power.

Linear linking for related traits (LLRT): A novel method for the harmonization of cognitive domains with no or few common items.

Harmonization means to make data comparable. Recent efforts to generate comparable data on cognitive performance of older adults from many different countries around the world have presented challenges for direct comparison. Neuropsychological instruments vary in many respects, including language, administration techniques and cultural differences, which all present important obstacles to assumptions regarding the presence of linking items. Item response theory (IRT) methods have been previously used to harmonize cross-national data on cognition, but these methods rely on linking items to establish the shared metric. We introduce an alternative approach for linking cognitive performance across two (or more) groups when the fielded assessments contain no items that can be reasonably considered linking items: Linear Linking for Related Traits (LLRT). We demonstrate this methodological approach in a sample from a single United States study split by educational attainment, and in two sets of cross-national comparisons (United States to England, and United States to India). All data were collected as part of the Harmonized Cognitive Assessment Protocol (HCAP) and are publicly available. Our method relies upon strong assumptions, and we offer suggestions for how the method can be extended to relax those assumptions in future work.

Associations between circulating cell-free mitochondrial DNA, inflammatory markers, and cognitive and physical outcomes in community dwelling older adults.

BACKGROUND: Dementia and frailty are common age-related syndromes often linked to chronic inflammation. Identifying the biological factors and pathways that contribute to chronic inflammation is crucial for developing new therapeutic targets. Circulating cell-free mitochondrial DNA (ccf-mtDNA) has been proposed as an immune stimulator and potential predictor of mortality in acute illnesses. Dementia and frailty are both associated with mitochondrial dysfunction, impaired cellular energetics, and cell death. The size and abundance of ccf-mtDNA fragments may indicate the mechanism of cell death: long fragments typically result from necrosis, while short fragments arise from apoptosis. We hypothesize that increased levels of necrosis-associated long ccf-mtDNA fragments and inflammatory markers in serum are linked to declines in cognitive and physical function, as well as increased mortality risk. RESULTS: Our study of 672 community-dwelling older adults revealed that inflammatory markers (C-Reactive Protein, soluble tumor necrosis factor alpha, tumor necrosis factor alpha receptor 1 [sTNFR1], and interleukin-6 [IL-6]) positively correlated with ccf-mtDNA levels in serum. Although cross-sectional analysis revealed no significant associations between short and long ccf-mtDNA fragments, longitudinal analysis demonstrated a connection between higher long ccf-mtDNA fragments (necrosis-associated) and worsening composite gait scores over time. Additionally, increased mortality risk was observed only in individuals with elevated sTNFR1 levels. CONCLUSION: In a community dwelling cohort of older adults, there are cross-sectional and longitudinal associations between ccf-mtDNA and sTNFR1 with impaired physical and cognitive function and increased hazard of death. This work suggests a role for long ccf-mtDNA as a blood-based marker predictive of future physical decline.

Application and validation of an algorithmic classification of early impairment in cognitive performance.

OBJECTIVE: Due to the long prodromal period for dementia pathology, approaches are needed to detect cases before clinically recognizable symptoms are apparent, by which time it is likely too late to intervene. This study contrasted two theoretically-based algorithms for classifying early cognitive impairment (ECI) in adults aged ≥50 enrolled in the Baltimore Longitudinal Study of Aging. METHOD: Two ECI algorithms were defined as poor performance (1 standard deviation [SD] below age-, sex-, race-, and education-specific means) in: (1) Card Rotations or California Verbal Learning Test (CVLT) immediate recall and (2) ≥1 (out of 2) memory or ≥3 (out of 6) non-memory tests. We evaluated concurrent criterion validity against consensus diagnoses of mild cognitive impairment (MCI) or dementia and global cognitive scores using receiver operating characteristic (ROC) curve analysis. Predictive criterion validity was evaluated using Cox proportional hazards models to examine the associations between algorithmic status and future adjudicated MCI/dementia. RESULTS: Among 1,851 participants (mean age = 65.2 ± 11.8 years, 50% women, 74% white), the two ECI algorithms yielded comparably moderate concurrent criterion validity with adjudicated MCI/dementia. For predictive criterion validity, the algorithm based on impairment in Card Rotations or CVLT immediate recall was the better predictor of MCI/dementia (HR = 3.53, 95%CI: 1.59-7.84) over 12.3 follow-up years. CONCLUSIONS: Impairment in visuospatial ability or memory may be capable of detecting early cognitive changes in the preclinical phase among cognitively normal individuals.

Measurement differences in the assessment of functional limitations for cognitive impairment classification across geographic locations.

INTRODUCTION: The measurement of dementia in cross-national contexts relies on the assessment of functional limitations. We aimed to evaluate the performance of survey items on functional limitations across culturally diverse geographic settings. METHODS: We used data from the Harmonized Cognitive Assessment Protocol Surveys (HCAP) in five countries (total N = 11,250) to quantify associations between items on functional limitations and cognitive impairment. RESULTS: Many items performed better in the United States and England compared to South Africa, India, and Mexico. Items on the Community Screening Instrument for Dementia (CSID) had the least variability across countries (SD = 0.73 vs. 0.92 [Blessed] and 0.98 [Jorm IQCODE]), but also the weakest associations with cognitive impairment (median odds ratio [OR] = 2.23 vs. 3.01 [Blessed] and 2.75 [Jorm IQCODE]). DISCUSSION: Differences in cultural norms for reporting functional limitations likely influences performance of items on functional limitations and may affect the interpretation of results from substantive studies. HIGHLIGHTS: There was substantial cross-country variation in item performance. Items from the Community Screening Instrument for Dementia (CSID) had less cross-country variability but lower performance. There was more variability in performance of instrumental activities of daily living (IADL) compared to activities of daily living (ADL) items. Variability in cultural expectations of older adults should be taken into account. Results highlight the need for novel approaches to assessing functional limitations.

Resilient Adaptation Strategies: Unveiling Older Adults' Coping Dynamics Amidst the COVID-19 Pandemic.

Older adults, who are particularly vulnerable to coronavirus disease 2019 (COVID-19), exhibit less stress and greater well-being than their younger peers. However, there have been no in-depth explorations of adaptive coping strategies among this population, nor has the role of frailty status been addressed. The current study examined stress and coping in 30 U.S. older adults (mean age = 81 years, range = 68 to 95 years) amidst the COVID-19 pandemic, uncovering themes of: (1) Pandemic Stresses: stresses experienced during the pandemic centered around social isolation and concern for others' well-being; (2) Resilience: older adults proved highly adaptable, with lifetime experience as a stress buffer; and (3) Silver Linings: older adults reported positive by-products, such as reconnecting with and a renewed appreciation for life and nature. Motivation for change and change itself centered around creating value and meaning in the present, especially around social isolation. Findings challenge existing ageist stereotypes, give insight into interventional design, and highlight the importance of ensuring infrastructural and societal support. [Journal of Gerontological Nursing, 49(12), 32-39.].

How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts.

The association between sex/gender and aging-related cognitive decline remains poorly understood because of inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to differential selection by dropout and death between men and women. We aimed to evaluate the impact of selection by dropout and death on the association between sex/gender and cognitive decline. We first compared the statistical methods most frequently used for longitudinal data, targeting either population estimands (marginal models fitted by generalized estimating equations) or subject-specific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 population-based studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996-2009), Personnes Âgées QUID (PAQUID; 1988-2014), the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (2003-2016), the Three-City Study (Bordeaux only; 1999-2016), the Washington Heights-Inwood Community Aging Project (WHICAP; 1992-2017), and the Whitehall II Study (2007-2016)) and 2 clinic-based studies (the Alzheimer's Disease Neuroimaging Initiative (ADNI; 2004-2017) and a nationwide French cohort study, MEMENTO (2011-2016)). We illustrate differences in the estimands of the association between sex/gender and cognitive decline in selected examples and highlight the critical role of differential selection by dropout and death. Using the same estimand, we then contrast the sex/gender-cognitive decline associations across cohorts and cognitive measures suggesting a residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the living population for assessing sex/gender differences while handling differential selection over time.

Delirium, changes in cognitive function, and risk of diagnosed dementia after kidney transplantation.

Kidney transplant (KT) recipients with delirium, a preventable surgical complication, are likely to reap cognitive benefits from restored kidney function, but may be more vulnerable to longer-term neurotoxic stressors post-KT (i.e., aging, immunosuppression). In this prospective cohort study, we measured delirium (chart-based), global cognitive function (3MS), and executive function (Trail Making Test Part B minus Part A) in 894 recipients (2009-2021) at KT, 1/3/6-months, 1-year, and annually post-KT. Dementia was ascertained using linked Medicare claims. We described repeated measures of cognitive performance (mixed effects model) and quantified dementia risk (Fine & Gray competing risk) by post-KT delirium. Of 894 recipients, 43(4.8%) had post-KT delirium. Delirium was not associated with global cognitive function at KT (difference = -3.2 points, 95%CI: -6.7, 0.4) or trajectories post-KT (0.03 points/month, 95%CI: -0.27, 0.33). Delirium was associated with worse executive function at KT (55.1 s, 95%CI: 25.6, 84.5), greater improvements in executive function <2 years post-KT (-2.73 s/month, 95%CI: -4.46,-0.99), and greater decline in executive function >2 years post-KT (1.72 s/month, 95%CI: 0.22, 3.21). Post-KT delirium was associated with over 7-fold greater risk of dementia post-KT (adjusted subdistribution hazard ratio = 7.84, 95%CI: 1.22, 50.40). Transplant centers should be aware of cognitive risks associated with post-KT delirium and implement available preventative interventions to reduce delirium risk.

The Measurement Error Elephant in the Room: Challenges and Solutions to Measurement Error in Epidemiology.

Measurement error, although ubiquitous, is uncommonly acknowledged and rarely assessed or corrected in epidemiologic studies. This review offers a straightforward guide to common problems caused by measurement error in research studies and a review of several accessible bias-correction methods for epidemiologists and data analysts. Although most correction methods require criterion validation including a gold standard, there are also ways to evaluate the impact of measurement error and potentially correct for it without such data. Technical difficulty ranges from simple algebra to more complex algorithms that require expertise, fine tuning, and computational power. However, at all skill levels, software packages and methods are available and can be used to understand the threat to inferences that arises from imperfect measurements.