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

Decline in weight and incident mild cognitive impairment Mayo Clinic study of aging

Copyright 2016 American Medical Association. All rights reserved. IMPORTANCE: Unintentional weight loss has been associated with risk of dementia. Because mild cognitive impairment (MCI) is a prodromal stage for dementia, we sought to evaluate whether changesin weight and body mass index (BMI) may predict incident MCI. OBJECTIVE: To investigate the association of change in weight and BMI with risk of MCI. DESIGN, SETTING, AND PARTICIPANTS: A population-based, prospective study of participants 70 years of age or older from the Mayo Clinic Study of Aging, which was initiated on October 1, 2004. Maximum weight and height in midlife (40-65 years of age) were retrospectively ascertained from the medical records of participants using a medical records-linkage system. The statistical analyses were performed between January and November 2015. MAINOUTCOMESAND MEASURES: Participants were evaluated for cognitive outcomes of normal cognition, MCI, or dementia at baseline and prospectively assessed for incident events at each 15-month evaluation. The association of rate of change in weight and BMI with risk of MCI was investigated using proportional hazards models. RESULTS: Over a mean follow-up of 4.4 years, 524 of 1895 cognitively normal participants developed incident MCI (50.3% were men; mean age, 78.5 years). The mean (SD) rate of weight change per decade from midlife to study entry was greater for participants who developed incident MCI vs those who remained cognitively normal (-2.0 [5.1] vs-1.2 [4.9] kg; P =.006). A greater decline in weight per decade was associated with an increased risk of incident MCI (hazard ratio [HR], 1.04 [95% CI, 1.02-1.06]; P \u3c.001) after adjusting for sex, education, and apolipoprotein E (APOE) e4 allele. A weight loss of 5 kg per decade corresponds to a 24% increase in risk of MCI (HR, 1.24). A higher decrease in BMI per decade was also associated with incident MCI (HR, 1.08 [95% CI, 1.03-1.13]; P =.003). CONCLUSIONS AND RELEVANCE: These findings suggest that increasing weight loss per decade from midlife to late life is a marker for MCI and may help identify persons at increased risk for MCI

Medical Doctors and Dementia: A Longitudinal Study

© 2020 The American Geriatrics Society OBJECTIVE: To examine the association between being a medical doctor (MD) and the risk of incident dementia. DESIGN: Cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: A total of 3460 participants (including 104 MDs), aged 70 years or older, of the population-based Mayo Clinic Study of Aging. MEASUREMENTS: Participants were randomly selected from the community and had comprehensive cognitive evaluations at baseline and approximately every 15 months to assess for diagnosis of dementia. For participants who withdrew from the follow-up, dementia diagnosis was also assessed using information available in their medical record. The associations were examined using Cox proportional hazards models, adjusting for sex, education, and apolipoprotein E ε4, using age as the time scale. RESULTS: MDs were older (vs “general population”), and most were males (93.3%). MDs without dementia at baseline did not have a significantly different risk for incident dementia (hazard ratio = 1.12; 95% confidence interval = 0.69-1.82; P =.64) compared to the general population. CONCLUSIONS: Although the study includes a small number of older, mainly male, MDs, it provides a preliminary insight on cognitive health later in life in MDs, while most previous studies examine the health of younger MDs. Larger longitudinal studies are needed to examine these associations and investigate if associations are modified by sex. J Am Geriatr Soc 68:1250–1255, 2020

Multimorbidity and neuroimaging biomarkers among cognitively normal persons

© 2016 American Academy of Neurology. Objective: To assess the cross-sectional association between multimorbidity and imaging biomarkers of brain pathology in the population-based Mayo Clinic Study of Aging (MCSA). Methods: The study consisted of 1,449 MCSA participants who were cognitively normal at the time of MRI. A subset of the participants also had 11C-Pittsburgh compound B (n 5 689) and 18fluorodeoxyglucose (n 5 688) PET scans available. Information on multimorbidity (defined as 2 chronic conditions) in the 5 years prior to the first imaging study was captured from the medical record using ICD-9 codes for chronic conditions and the Rochester Epidemiology Project medical records linkage system. The cross-sectional association of multimorbidity and imaging biomarkers was examined using logistic and linear regression models. Results: Among 1,449 cognitively normal participants (mean age 79 years; 50.9% men), 85.4% had multimorbidity (2 chronic conditions). Multimorbidity and severe multimorbidity (4 chronic conditions) were associated with abnormal Alzheimer disease (AD) signature meta-region of interest (meta-ROI) 18F-FDG hypometabolism (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.10-3.77 and OR 2.22; 95% CI 1.18-4.16, respectively), and with abnormal AD signature MRI cortical thickness (OR 1.53; 95% CI 1.09-2.16 and OR 1.76; 95% CI 1.24-2.51, respectively), but was not associated with amyloid accumulation. Conclusions: Multimorbidity was associated with brain pathology through mechanisms independent of amyloid deposition and such neuronal injury and pathology was present before any symptomatic evidence of cognitive impairment. Longitudinal follow-up will provide insights into potential causal associations of multimorbidity with changes in brain pathology

Mediterranean Diet, Its Components, and Amyloid Imaging Biomarkers

© 2018 - IOS Press and the authors. All rights reserved. Background: There is accumulating evidence suggesting that diet may play a role in preventing or delaying cognitive decline and dementia, but the underlying biological mechanisms are not well understood. Objectives: To examine the cross-sectional associations of the Mediterranean diet (MeDi) and its components with 11 C-PiB-PET scan measures of amyloid-β (Aβ) deposition. Methods: The study consisted of 278 Mayo Clinic Study of Aging participants 70+ years old, who were cognitively unimpaired (CU) at the time of completion of the Food Frequency Questionnaire (FFQ) and when they underwent PET imaging. Adherence to the MeDi was assessed by computing the MeDi score for each participant. All scans were performed after the FFQ completion; median [IQR] time between FFQ and Aβ PET was 3.5 (1.4) years. Z-scores were created for component, macro- and micronutrients measured. Linear and logistic regression models were adjusted for age, sex, education, apolipoprotein E (APOE) ϵ4 allele carrier status, time interval between the FFQ completion and PET scan, and total energy intake. Results: Participants\u27 median age at FFQ was 77.7 years (55.8% men; 26.6% with an APOE ϵ4 allele). Higher MeDi score (linear regression slope (beta):-0.035, p = 0.012; per standard deviation increase), vegetable intake (beta:-0.043, p = 0.002), intake of vitamin A (beta:-0.041, p = 0.003) or β-carotene (beta: -0.039, p = 0.005) from food sources and moderate alcohol consumption (beta: -0.074, p = 0.03) were associated with lower 11 C-PiB standardized uptake value ratio. Conclusion: Findings are consistent with previous studies suggesting that higher adherence to a MeDi pattern and higher vegetable consumption are associated with better neuroimaging biomarker profile. Prospective studies are needed to validate current findings

Association of neighborhood socioeconomic disadvantage and cognitive impairment

INTRODUCTION: We investigated the association of the area deprivation index (ADI) with cognitive decline, mild cognitive impairment (MCI), and dementia in older adults (≥50 years old). ADI is a neighborhood socioeconomic disadvantage measure assessed at the census block group level. METHODS: The study included 4699 participants, initially without dementia, with available ADI values for 2015 and at least one study visit in 2008 through 2018. Using logistic regression and Cox proportional hazards models with age as the time scale, we assessed the odds for MCI and the risk for dementia, respectively. RESULTS: In cognitively unimpaired (CU) adults at baseline, the risk for progression to dementia increased for every decile increase in the ADI state ranking (hazard ratio = 1.06, 95% confidence interval (1.01-1.11), P = .01). Higher ADI values were associated with subtly faster cognitive decline. DISCUSSION: In older CU adults, higher baseline neighborhood socioeconomic deprivation levels were associated with progression to dementia and slightly faster cognitive decline. HIGHLIGHTS: The study used area deprivation index, a composite freely available neighborhood deprivation measure. Higher levels of neighborhood deprivation were associated with greater mild cognitive impairment odds. Higher neighborhood deprivation levels were associated with higher dementia risk

Prevalence and outcomes of amyloid positivity among persons without dementia in a longitudinal, population-based setting

© 2018 American Medical Association. All rights reserved. IMPORTANCE Brain amyloid deposition is a marker of Alzheimer disease (AD) pathology. The population-based prevalence and outcomes of amyloid positivity in a population without dementia are important for understanding the trajectory of amyloid positivity to clinically significant outcomes and for designing AD prevention trials. OBJECTIVE To determine prevalence and outcomes of amyloid positivity in a population without dementia. DESIGN, SETTING, AND PARTICIPANTS In the prospective, population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, participants without dementia were randomly selected from the county population and were clinically and cognitively evaluated at baseline and every 15 months from August 1, 2008, to September 18, 2018. They were also invited to undergo carbon11-Pittburgh compound B positron emission tomography (PET) imaging. EXPOSURES Amyloid positivity (defined as a standardized uptake value ratio \u3e1.42 on PET). MAIN OUTCOMES AND MEASURES Prevalence of amyloid positivity in the Olmsted County population without dementia and risk of progression from no cognitive impairment (ie, normal cognition for age) to incident amnestic MCI (aMCI) and from MCI or aMCI to incident AD dementia. RESULTS Of 3894 participants, 1671 underwent PET imaging and were included in the study; 2198 did not undergo imaging, and 25 were excluded for other reasons. The mean (SD) age of participants was 71.3 (9.8) years; 892 (53.4%) were men, and 179 (10.7%) had prevalent MCI. The prevalence of amyloid positivity without cognitive impairment in the population without dementia increased from 2.7%(95%CI, 0.5%to 4.9%) in persons aged 50 to 59 years to 41.3%(95%CI, 33.4%to 49.2%) in those aged 80 to 89 years at baseline. Prevalence of amyloid-positive MCI in the population without dementia increased from 0% in persons aged 50 to 59 years to 16.4%(95%CI, 10.3%to 22.5%) in those aged 80 to 89 years. The incident aMCI risk increased more than 2-fold in participants without cognitive impairment who were amyloid positive vs those who were amyloid negative (hazard ratio [HR], 2.26; 95%CI, 1.52 to 3.35; P \u3c .001). The risk of AD dementia was 1.86 (95%CI, 0.89 to 3.88; P = .10) for amyloid-positive participants with MCI vs amyloid-negative participants with MCI, 1.63 (95% CI, 0.78 to 3.41; P = .20) for participants with aMCI who were amyloid positive vs amyloid negative, and 2.56 (95%CI, 1.35 to 4.88; P = .004) for amyloid-positive participants who were either without cognitive impairment or had aMCI vs those who were amyloid negative. Global cognitive and memory domain z scores declined significantly in amyloid-positive individuals during follow-up. The mean (SD) follow-up time from baseline was 3.7 (1.9) years to incident aMCI and 3.8 (2.0) years to incident AD dementia. CONCLUSIONS AND RELEVANCE Population-based prevalence of amyloid-positive status and progression rates of amyloid positivity provide valid information for designing AD prevention trials and assessing the public health outcomes of AD prevention and interventions

The association of multimorbidity with preclinical AD stages and SNAP in cognitively unimpaired persons

© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. Background: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer’s disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer’s disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age). Methods: The study included 1,535 cognitively unimpaired participants with multimorbidity, 11C-PiB positron emission topography and magnetic resonance imaging data available. Abnormal (elevated) 11C-PiB-positron emission topography retention ratio (A+; standardized uptake value ratio \u3e1.42) and abnormal (reduced) Alzheimer’s disease signature cortical thickness (N+; \u3c2.67 mm) were used to define biomarker combinations (A−N−, A+N−, A−N+, A+N+). Chronic medical conditions were ascertained by using the Rochester Epidemiology Project medical records linkage system and International Classification of Diseases criteria. Cross-sectional associations were examined using multinomial logistic regression models adjusting for age, sex, education, and apolipoprotein E ℇ4 allele status. Results: Frequency of A+, N+, A+N+, and A−N+ biomarker groups increased significantly with increasing number of chronic conditions. Multimorbidity was significantly associated with A+N+ (vs A−N−; odds ratio, 1.76, 95% confidence interval 1.02, 2.90) and A−N+ (vs A− N−; odds ratio, 2.16, 95% confidence interval 1.47, 3.18). There was a dose–response relationship between increasing number of chronic conditions (eg, 0–1, 2–3, and 4+) and the odds of A+N+ and A−N+ (vs A−N−). Conclusions: Multimorbidity was associated with biomarker combinations that included neurodegeneration with or without elevated amyloid deposition (ie, A−N+, A+N+). The associations should be validated in longitudinal studies