Kelly K. Edwards

Hypothyroidism and Risk of Mild Cognitive Impairment in Elderly Persons: A Population-Based Study

IMPORTANCE An association of clinical and subclinical hypothyroidism with mild cognitive impairment (MCI) has not been established. OBJECTIVE To evaluate the association of clinical and subclinical hypothyroidism with MCI in a large population-based cohort. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional, population-based study was conducted in Olmsted County, Minnesota. Randomly selected participants were aged 70 to 89 years on October 1, 2004, and were without documented prevalent dementia [CORRECTED]. A total of 2050 participants were evaluated and underwent in-person interview, neurologic evaluation, and neuropsychological testing to assess performance in memory, attention/executive function, and visuospatial and language domains. Participants were categorized by consensus as being cognitively normal, having MCI, or having dementia according to published criteria. Clinical and subclinical hypothyroidism were ascertained from a medical records linkage system. MAIN OUTCOMES AND MEASURES Association of clinical and subclinical hypothyroidism with MCI. RESULTS Among 1904 eligible participants, the frequency of MCI was 16% in 1450 individuals with normal thyroid function, 17% in 313 persons with clinical hypothyroidism, and 18% in 141 individuals with subclinical hypothyroidism. After adjusting for covariates (age, educational level, sex, apolipoprotein E ε4, depression, diabetes mellitus, hypertension, stroke, body mass index, and coronary artery disease) we found no significant association between clinical or subclinical hypothyroidism and MCI (odds ratio [OR], 0.99 [95% CI, 0.66-1.48] and 0.88 [0.38-2.03], respectively). No effect of sex interaction was seen on these effects. In stratified analysis, the odds of MCI with clinical and subclinical hypothyroidism among men was 1.02 (95% CI, 0.57-1.82) and 1.29 (0.68-2.44) and, among women, was 1.04 (0.66-1.66) and 0.86 (0.37-2.02), respectively. CONCLUSIONS AND RELEVANCE In this population-based cohort of elderly people, neither clinical nor subclinical hypothyroidism was associated with MCI. Our findings need to be validated in a separate setting using the published criteria for MCI and confirmed in a longitudinal study.

Comparison of Gait Parameters for Predicting Cognitive Decline: The Mayo Clinic Study of Aging

BACKGROUND Previous studies reported that slower gait speed might predict cognitive impairment and dementing illnesses, supporting the role of gait speed as a possible subclinical marker of cognitive impairment. However, the predictive value of other gait parameters for cognitive decline is unclear. OBJECTIVE To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample. METHODS The analysis included 3,426 cognitively normal participants enrolled in the Mayo Clinic Study of Aging. At baseline and every 15 months (mean follow-up = 1.93 years), participants had a study coordinator evaluation, neurological examination, and a neuropsychological assessment using nine tests that covered four domains. Gait parameters were assessed with the GAITRite® instrument. General linear mixed effects models were used to compute the annualized rate of change in cognitive domain z-scores, controlling for age, sex, education, depression, comorbidities, body mass index, APOE ɛ4 allele, and visit number, and excluding individuals with a history of stroke, alcoholism, Parkinsons disease, subdural hematoma, and normal pressure hydrocephalus. RESULTS Spatial (stride length), temporal (ambulatory time, gait speed, step count, cadence, double support time), and spatiotemporal (cadence) gait parameters, and greater intraindividual variability in stride length, swing time, and stance time were associated with a significant decline in global cognition and in specific domains including memory, executive function, visuospatial, and language. CONCLUSIONS Spatial, temporal, and spatiotemporal measures of gait and greater variability of gait parameters were associated with and predictive of both global- and domain-specific cognitive decline.

Performance of the CogState computerized battery in the Mayo Clinic Study on Aging

The feasibility and validity of brief computerized cognitive batteries at the population‐level are unknown.

Modified Masaoka Stage and Size Are Independent Prognostic Predictors in Thymoma and Modified Masaoka Stage Is Superior to Histopathologic Classifications

Introduction: The prognostic value of histopathologic classifications of thymoma is debated. Problematic reproducibility might cause this controversy. We studied the prognostic significance of three histopathologic classifications of thymomas after three thoracic pathologists agreed upon thymoma subtype and invasion. We also compared the outcome to established prognostic parameters. Methods: Patients, surgically treated for thymic epithelial neoplasm at Mayo Clinic (1942–2008), were staged according to the modified Masaoka staging and the recently proposed staging by Moran. Three thoracic pathologists independently classified all cases according to the World Health Organization, Bernatz, and proposed Suster and Moran classification. Only thymoma that all three pathologists diagnosed as the same histopathologic subtype and extent of invasion were included in outcome analysis. Results: In 214 (proposed Suster and Moran classification), 145 (World Health Organization classification), and 120 cases (Bernatz classification), reviewers agreed upon subtype of thymoma and invasion and follow-up was available. Median follow-up time was 7.5–7.7 years (range between classifications). All histopathologic classifications were associated with overall survival (OS) and disease-free survival (p ⩽ 0.0001 to p = 0.048); only Bernatz classification was independent of modified Masaoka staging associated with OS (p = 0.04). Modified Masaoka stage predicted outcome independent of all histopathologic classifications and resection status and strongly correlated with the proposed Moran stage (correlation coefficient, 0.95). Thymoma size and age were prognostic parameters for OS independent of any histopathologic classification. Conclusions: Histopathologic classifications of thymomas are associated with prognosis but are in general not independent predictors of outcome. Modified Masaoka stage and proposed Moran staging are independent prognostic parameters for thymoma and superior to histopathologic classifications.

Reproducibility of 3 histologic classifications and 3 staging systems for thymic epithelial neoplasms and its effect on prognosis

Data regarding the prognostic significance of the histopathologic classifications of thymic epithelial neoplasms are contradictory, perhaps reflecting issues in reproducibility. We studied the effect of reproducibility of 3 histopathologic classifications on prognosis and investigated the interobserver agreement on invasion and its effect on staging and prognosis. A total of 456 patients who underwent surgery for thymic epithelial neoplasm at Mayo Clinic Rochester (1942 to 2008) were staged (modified Masaoka, proposed Moran, proposed IASLC/ITMIG) and independently classified by 3 thoracic pathologists (World Health Organization, proposed Suster & Moran [S&M], and Bernatz). Interobserver agreement was moderate to substantial for all histopathologic classifications (&kgr; values: 0.65, 0.52, 0.74 for World Health Organization, Bernatz, and S&M, respectively). All histopathologic classifications were significant for overall survival (OS) and disease-free survival (DFS) (all reviewers). If adjusted for Masaoka, only Bernatz classification for one reviewer and all histopathologic classifications for another reviewer were significant for OS. Interobserver agreement for invasion was substantial (&kgr;=0.61) and almost perfect for Masaoka, Moran, and IASLC/ITMIG stage (&kgr; values: 0.85, 0.81, and 0.92, respectively). The correlation coefficient for Masaoka and Moran staging was 0.93. Masaoka and IASLC/ITMIG staging were significant for OS and DFS (all reviewers). If adjusted for any histopathologic classification, Masaoka was significant for OS and DFS (all reviewers). In conclusion, reproducibility of histopathologic classifications has some effect on outcome. S&M is the most reproducible classification. Reproducibility of invasion has no effect on the prognostic value of staging. Masaoka, Moran, and IASLC/ITMIG staging are almost perfectly reproducible. The strong correlation between Masaoka and Moran staging suggests similar prognostic strength.

Subjective cognitive decline and risk of MCI: The Mayo Clinic Study of Aging

Objective We investigated different dimensions of subjective cognitive decline (SCD) to determine which was the best prognostic risk factor for incident mild cognitive impairment (MCI) among cognitively unimpaired participants. Methods We included 1,167 cognitively unimpaired participants, aged 70 to 95 years, from the Mayo Clinic Study of Aging based on 2 concurrent SCD scales (part of the Blessed memory test and the 39-item Everyday Cognition [ECog] scale, which included a validated 12-item derivative) and a single question assessing worry about cognitive decline. We evaluated multiple ways to dichotomize scores. In continuous models, we compared average scores on 4 ECog domains and multidomain (39- and 12-item) ECog scores. Cox proportional hazards models were used to assess the association between each measure and risk of MCI in models adjusted for objective memory performance, depression, anxiety, sex, APOE ε4 carriership, and medical comorbidities. Results It was possible to select a substantial group of participants (14%) at increased risk of incident MCI based on combined baseline endorsement of any consistent SCD on the ECog (any item scored ≥3; 12-item ECog hazard ratio [HR] 2.17 [95% confidence interval 1.51–3.13]) and worry (HR 1.79 [1.24–2.58]) in an adjusted model combining these dimensions. In continuous models, all ECog domains and the multidomain scores were associated with risk of MCI with a small advantage for multidomain SCD (12-item ECog HR 2.13 [1.36–3.35] per point increase in average score). Information provided by the informant performed comparable to self-perceived SCD. Conclusion Prognostic value of SCD for incident MCI improves when both consistency of SCD and associated worry are evaluated.

Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging

To determine the cross‐sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics.

ASPECTS OF SUBJECTIVE COGNITIVE DECLINE THAT PREDICT INCIDENT MCI IN THE MAYO CLINC STUDY OF AGING

to perform a cross-cultural adaptation of a Brazilian version of Cognitive Function Instrument (CFI). It is an instrument developed by the Alzheimer’s Disease Cooperative Study Group for evaluation of Subjective Cognitive Decline. The project consisted of a cross-sectional study where the original instrument in English was translated and adapted into the Portuguese language. The sample consisted of individuals recruited from among the patients’ caregiver from the Cognitive Neurology outpatient clinic of the Medical School of University of S~ao Paulo.Results:This transcultural translation and adaptation process consisted of six stages: initial translation by two translators, synthesis, back translation by two others translators, review by a committee of experts and pretesting of a draft. The preliminary version was applied in 37 individuals. The mean age was 63.5 years with an average of 10.4 years of schooling. In final review, decisions taken by the committee of experts sought to obtain semantic, idiomatic, experimental and conceptual equivalence between the source and the translated version. Throughout the process, all problems found were solved to ensure the quality of the instrument and its appropriateness to the target population. Conclusions:We elaborated a translated and adapted version of an instrument that can be applied to evaluate Subjective Cognitive Decline in the Brazilian population. This instrument is being validated in a cohort of normal elderly without and with subjective cognitive decline and compared with biomarkers of Alzheimer’s disease.