Phenoconversion from probable rapid eye movement sleep behavior disorder to mild cognitive impairment to dementia in a population-based sample

© 2017 The Authors Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies

Frailty and Mortality Outcomes in Cognitively Normal Older People: Sex Differences in a Population-Based Study

© 2016, the Authors Journal compilation. Objectives To characterize frailty in cognitively normal older adults at baseline and to investigate the relationship between frailty and mortality. Design Population-based prospective cohort study: Mayo Clinic Study of Aging. Setting Olmsted County, Minnesota. Participants Cognitively normal older persons aged 70 and older (mean age 78.8 ± 5.2, 50.2% male; N = 2,356). Measurements Frailty was assessed at baseline using a 36-item Frailty Index. Four frailty subgroups were identified based on the Frailty Index (≤0.10 (fit), 0.11-0.20 (at risk), 0.21-0.30 (frail), \u3e0.30 (frailest)). All participants underwent comprehensive clinical and cognitive assessments. The association between frailty and mortality was assessed using Cox proportional hazards models. Results The median Frailty Index was 0.17 (interquartile range 0.11-0.22). Frailty increased with age and was more common in older men than in older women. Over a median follow-up of 6.5 years (range 7 days to 8.9 years), 500 of the 2,356 participants died, including 292 men. The frailest participants had the greatest risk of death (hazard ratio (HR) = 3.91, 95% confidence interval (CI) = 2.69-5.68). The association was stronger in women (HR = 5.26, 95% CI = 2.88-9.61) than men (HR = 3.15, 95% CI = 1.98-5.02). Conclusion Baseline frailty was common, especially in older men, and increased with age. Frailty was associated with significantly greater risk of death, particularly in women. These sex differences should be considered when designing a geriatric care plan

Validation of the Telephone Interview for Cognitive Status-modified in Subjects with Normal Cognition, Mild Cognitive Impairment, or Dementia

Background: The telephone assessment of cognitive functions may reduce the cost and burden of epidemiological studies. Methods: We validated the Telephone Interview for Cognitive Status-modified (TICS-m) using an extensive in-person assessment as the standard for comparison. Clinical diagnoses of normal cognition, mild cognitive impairment (MCI), or dementia were established by consensus of physician, nurse, and neuropsychological assessments. Results: The extensive in-person assessment classified 83 persons with normal cognition, 42 persons with MCI, and 42 persons with dementia. There was considerable overlap in TICS-m scores among the three groups. Receiver operating characteristic curves identified ≤31 as the optimal cutoff score to separate subjects with MCI from subjects with normal cognition (sensitivity = 71.4%; subjects with dementia excluded), and ≤27 to separate subjects with dementia from subjects with MCI (sensitivity = 69.0%; subjects with normal cognition excluded). The TICS-m performed well when subjects with MCI were pooled either with subjects with dementia (sensitivity = 83.3%) or with subjects with normal cognition (sensitivity = 83.3%). Conclusions: Although the TICS-m performed well when using a dichotomous classification of cognitive status, it performed only fairly in separating MCI from either normal cognition or dementia. The TICS-m should not be used as a free-standing tool to identify subjects with MCI, and it should be used with caution as a tool to detect dementia. © 2009 S. Karger AG, Basel

Computer activities, physical exercise, aging, and mild cognitive impairment: A population-based Study

Objective: To examine the association between computer use, physical exercise, aging, and mild cognitive impairment (MCI). Patients and Methods: The Mayo Clinic Study of Aging is a population-based study of aging and MCI in Olmsted County, Minnesota. The study sample consists of a random sample of 926 nondemented individuals aged 70 to 93 years who completed self-reported questionnaires on physical exercise, computer use, and caloric intake within 1 year of the date of interview. The study was conducted from April 1, 2006, through November 30, 2008. An expert consensus panel classified each study participant as cognitively normal or having MCI on the basis of published criteria. Results: Using a multivariable logistic regression model, we examined the impact of the presence during the study period of 2 lifestyle factors (physical exercise and computer use) after adjusting for a third lifestyle factor (caloric intake) on aging and MCI. We also adjusted for age, sex, education, medical comorbidity, and depression. The median daily caloric intake was significantly higher in participants with MCI than in controls (odds ratio, 1.04;95% confidence interval, 1.02-1.06; P=.001). Participants who engaged in both moderate physical exercise and computer use had significantly decreased odds of having MCI (odds ratio [95% confidence interval], 0.36 [0.20-0.68]) compared with the reference group. In the interaction analyses, there was an additive interaction (P=.012) but not multiplicative interaction (P=.780). Conclusion: In this population-based sample, the presence of both physical exercise and computer use as assessed via survey was associated with decreased odds of having MCI, after adjustment for caloric intake and traditional confounders. © 2012 Mayo Foundation for Medical Education and Research

Association of duration and severity of diabetes mellitus with mild cognitive impairment

Background: It remains unknown whether diabetes mellitus (DM) is a risk factor for mild cognitive impairment (MCI). Objective: To investigate the association of DM with MCI using a population-based case-control design. Design: Population-based case-control study. Setting: Academic research. Participants: Our study was conducted, among subjects aged 70 to 89 years on October 1, 2004, who were randomly selected from the Olmsted County (Minnesota) population. Main Outcome Measure: We administered to all participants a neurologic examination, the Clinical Dementia Rating Scale, and a neuropsychological evaluation (including 9 tests in 4 cognitive domains) to diagnose normal cognition, MCI, or dementia. We assessed history of DM, DM treatment, and DM complications by interview, and we measured fasting blood glucose levels. History of DM was also confirmed using a medical records linkage system. Results: We compared 329 subjects having MCI with 1640 subjects free of MCI and dementia. The frequency of DM was similar in subjects with MCI (20.1%) and in subjects without MCI (17.7%) (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.85-1.57). However, MCI was associated with onset of DM before age 65 years (OR, 2.20; 95% CI, 1.29-3.73), DM duration of 10 years or longer (OR, 1.76; 95% CI, 1.16-2.68), treatment with insulin (OR, 2.01; 95% CI, 1.22-3.31), and the presence of DM complications (OR, 1.80; 95% CI, 1.13-2.89) after adjustment for age, sex, and education. Analyses using alternative definitions of DM yielded consistent findings. Conclusion: These findings suggest an association of MCI with earlier onset, longer duration, and greater severity of DM. ©2008 American Medical Association. All rights reserved

Association between olfactory dysfunction and amnestic mild cognitive impairment and Alzheimer disease dementia

© 2016 American Medical Association. IMPORTANCE To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. OBJECTIVE To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia. DESIGN, SETTING, AND PARTICIPANTS Participants enrolled in the population-based, prospectiveMayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI [aMCI] and nonamnestic MCI [naMCI]), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. MAIN OUTCOMES AND MEASURES Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures. RESULTS Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4%were men, the mean duration of education was 14.3 years, and 25.4%were APOE e4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants.We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95%CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend \u3c.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles. Compared with Q4, HR (95%CI) estimates were 3.02 (1.06-8.57) for Q3 (P = .04); 3.63 (1.19-11.10) for Q2 (P = .02); and 5.20 (1.90-14.20) for Q1 (P = .001). After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10 [95%CI, 1.04-1.16]; P \u3c .001) and improved the model concordance. CONCLUSIONS AND RELEVANCE Olfactory impairment is associated with incident aMCI and progression from aMCI to AD dementia. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress

Physical exercise, aging, and mild cognitive impairment a population-based study

Background: Physical exercise is associated with decreased risk of dementia and Alzheimer disease. Objective: To investigate whether physical exercise is associated with decreased risk of mild cognitive impairment (MCI). Design: Population-based case-control study. Setting: The Mayo Clinic Study of Aging, an ongoing population-based cohort study in Olmsted County, Minnesota. Participants: A total of 1324 subjects without dementia who completed a Physical Exercise Questionnaire. Main Outcome Measures: An expert consensus panel classified each subject as having normal cognition or MCI based on published criteria. Results: We compared the frequency of physical exercise among 198 subjects with MCI with that among 1126 subjects with normal cognition and adjusted the analyses for age, sex, years of education, medical comorbidity, and depression. The odds ratios for any frequency of moderate exercise were 0.61 (95% confidence interval, 0.43-0.88; P=.008) for midlife (age range, 50-65 years) and 0.68 (95% confidence interval, 0.49-0.93; P=.02) for late life. The findings were consistent among men and women. Light exercise and vigorous exercise were not significantly associated with decreased risk of MCI. Conclusion: In this population-based case-control study, any frequency of moderate exercise performed in midlife or late life was associated with a reduced odds of having MCI. ©2010 American Medical Association. All rights reserved