Brain amyloid, cortical thickness, and changes in activities of daily living.

OBJECTIVE: To examine the association of baseline elevated brain amyloid and neurodegeneration with changes in activities of daily living in participants without dementia (ND; i.e., cognitively unimpaired and participants with mild cognitive impairment) at baseline in the population-based Mayo Clinic Study of Aging. METHODS: We included 1747 ND participants with 11 C-PiB PET and MR imaging in the study, with data on activities of daily living (as assessed by the Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating scale Sum of Boxes for functional domains (CDR-SOB (functional)), with a median (range) of 4.3 (0.0-12.7) years of follow-up. Abnormal (elevated; A+) 11 C-PiB-PET retention ratio was defined as standardized uptake value ratio ≥ 1.48, and abnormal (reduced) AD signature cortical thickness as ≤ 2.68 mm (neurodegeneration; N+). Associations were examined with mixed effects models, adjusting for age, sex, education, apolipoprotein E ε4 allele carrier status, and global cognitive z-score. RESULTS: Mean age (SD) was 71.4 years (10.1), 46.7% were females, 195 (11.2%) had A+N-, 442 (25.3%) had A-N+, and 339 (19.4%) had A+N+ biomarkers. The A+N+ group had the largest annualized change in the FAQ score from baseline (difference in annual change A+N+ vs. A-N-; ß (SE): 0.80 (0.07)); associations were substantially attenuated when a time-varying global cognitive composite was included in the model (A+N+ vs. A-N-; ß (SE): 0.31 (0.05)). CDR-SOB (functional) findings partly agreed with FAQ score findings. INTERPRETATION: The longitudinal increase in functional limitations is greater for individuals with abnormal neuroimaging biomarkers, especially for those with both elevated brain amyloid and neurodegeneration.

Medical Doctors and Dementia: A Longitudinal Study.

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.

Informant-based hearing difficulties and the risk for mild cognitive impairment and dementia.

BACKGROUND: hearing loss has been associated with mild cognitive impairment (MCI) and dementia. Studies have not assessed whether hearing difficulties (HD) that interfere with daily activities as reported by partners can be a marker for increased risk for cognitive decline and impairment. OBJECTIVE: to assess the cross-sectional and longitudinal associations between informant-based HD, which interfere with daily activities and the risk for MCI and dementia. METHODS: the study included 4812 participants without dementia, enrolled in the Mayo Clinic Study of Aging (mean age (SD) 73.7 (9.6) years) with cognitive evaluation and informant-based report on participant's HD that interfere significantly with daily activities at baseline and for every 15 months. Cox proportional hazards models (utilising time-dependent HD status and age as the time scale) were used to examine HD and the risk for MCI or dementia, and mixed-effects models (allowing for random subject-specific intercepts and slopes) were used to examine the relationship between HD and cognitive decline. RESULTS: about, 981 participants had HD and 612 (12.7%) had prevalent MCI at baseline; 759 participants developed incident MCI and 273 developed incident dementia. In cognitively unimpaired participants at baseline, those with HD had higher risk for MCI (hazard ratio [HR] = 1.29, 95% confidence interval [CI] (1.10, 1.51), P = 0.002; adjusting for sex, years of education). In participants without dementia, those with HD had higher risk for dementia (HR: 1.39, 95% CI, (1.08-1.79), P = 0.011; adjusting sex and education). In individuals with MCI, HD was associated with modestly greater cognitive decline. CONCLUSIONS: informant-based HD was associated with increased risk for MCI and dementia.

Prevalence of Biologically vs Clinically Defined Alzheimer Spectrum Entities Using the National Institute on Aging-Alzheimer's Association Research Framework.

Importance: A National Institute on Aging-Alzheimer's Association (NIA-AA) workgroup recently published a research framework in which Alzheimer disease is defined by neuropathologic or biomarker evidence of ß-amyloid plaques and tau tangles and not by clinical symptoms. Objectives: To estimate the sex- and age-specific prevalence of 3 imaging biomarker-based definitions of the Alzheimer disease spectrum from the NIA-AA research framework and to compare these entities with clinically defined diagnostic entities commonly linked with Alzheimer disease. Design, Setting, and Participants: The Mayo Clinic Study of Aging (MCSA) is a population-based cohort study of cognitive aging in Olmsted County, Minnesota. The MCSA in-person participants (n = 4660) and passively ascertained (ie, through the medical record rather than in-person) individuals with dementia (n = 553) aged 60 to 89 years were included. Subsets underwent amyloid positron emission tomography (PET) (n = 1524) or both amyloid and tau PET (n = 576). Therefore, this study included 3 nested cohorts examined between November 29, 2004, and June 5, 2018. Data were analyzed between February 19, 2018, and March 26, 2019. Main Outcomes and Measures: The sex- and age-specific prevalence of the following 3 biologically defined diagnostic entities was estimated: Alzheimer continuum (abnormal amyloid regardless of tau status), Alzheimer pathologic change (abnormal amyloid but normal tau), and Alzheimer disease (abnormal amyloid and tau). These were compared with the prevalence of 3 clinically defined diagnostic groups (mild cognitive impairment or dementia, dementia, and clinically defined probable Alzheimer disease). Results: The median (interquartile range) age was 77 (72-83) years in the clinical cohort (n = 5213 participants), 77 (70-83) years in the amyloid PET cohort (n = 1524 participants), and 77 (69-83) years in the tau PET cohort (n = 576 participants). There were roughly equal numbers of women and men. The prevalence of all diagnostic entities (biological and clinical) increased rapidly with age, with the exception of Alzheimer pathologic change. The prevalence of biological Alzheimer disease was greater than clinically defined probable Alzheimer disease for women and men. Among women, these values were 10% (95% CI, 6%-14%) vs 1% (95% CI, 1%-1%) at age 70 years and 33% (95% CI, 25%-41%) vs 10% (95% CI, 9%-12%) at age 85 years (P < .001). Among men, these values were 9% (95% CI, 5%-12%) vs 1% (95% CI, 0%-1%) at age 70 years and 31% (95% CI, 24%-38%) vs 9% (95% CI, 8%-11%) at age 85 years (P < .001). The only notable difference by sex was a greater prevalence of the mild cognitive impairment or dementia clinical category among men than women. Conclusions and Relevance: Results of this study suggest that biologically defined Alzheimer disease is more prevalent than clinically defined probable Alzheimer disease at any age and is 3 times more prevalent at age 85 years among both women and men. This difference is mostly driven by asymptomatic individuals with biological Alzheimer disease. These findings illustrate the magnitude of the consequences on public health that potentially exist by intervening with disease-specific treatments to prevent symptom onset.

Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults.

OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

Associations of Amyloid, Tau, and Neurodegeneration Biomarker Profiles With Rates of Memory Decline Among Individuals Without Dementia.

Importance: A National Institute on Aging and Alzheimer's Association workgroup proposed a research framework for Alzheimer disease in which biomarker classification of research participants is labeled AT(N) for amyloid, tau, and neurodegeneration biomarkers. Objective: To determine the associations between AT(N) biomarker profiles and memory decline in a population-based cohort of individuals without dementia age 60 years or older, and to determine whether biomarkers provide incremental prognostic value beyond more readily available clinical and genetic information. Design, Setting, and Participants: Population-based cohort study of cognitive aging in Olmsted County, Minnesota, that included 480 nondemented Mayo Clinic Study of Aging participants who had a clinical evaluation and amyloid positron emission tomography (PET) (A), tau PET (T), and magnetic resonance imaging (MRI) cortical thickness (N) measures between April 16, 2015, and November 1, 2017, and at least 1 clinical evaluation follow-up by November 12, 2018. Exposures: Age, sex, education, cardiovascular and metabolic conditions score, APOE genotype, and AT(N) biomarker profiles. Each of A, T, or (N) can be abnormal (+) or normal (-), resulting in 8 AT(N) profiles. Main Outcomes and Measures: Primary outcome was a composite memory score measured longitudinally at 15-month intervals. Analyses measured the associations between predictor variables and the memory score, and whether AT(N) biomarker profiles significantly improved prediction of memory z score rates of change beyond a model with clinical and genetic variables only. Results: Participants were followed up for a median of 4.8 years (interquartile range [IQR], 3.8-5.1) and 44% were women (211/480). Median (IQR) ages ranged from 67 years (65-73) in the A-T-(N)- group to 83 years (76-87) in the A+T+(N)+ group. Of the participants, 92% (441/480) were cognitively unimpaired but the A+T+(N)+ group had the largest proportion of mild cognitive impairment (30%). AT(N) biomarkers improved the prediction of memory performance over a clinical model from an R2 of 0.26 to 0.31 (P < .001). Memory declined fastest in the A+T+(N)+, A+T+(N)-, and A+T-(N)+ groups compared with the other 5 AT(N) groups (P = .002). Estimated rates of decline in the 3 fastest declining groups were -0.13 (95% CI, -0.17 to -0.09), -0.10 (95% CI, -0.16 to -0.05), and -0.10 (95% CI, -0.13 to -0.06) z score units per year, respectively, for an 85-year-old APOE ε4 noncarrier. Conclusions and Relevance: Among older persons without baseline dementia followed for a median of 4.8 years, a prediction model that included amyloid PET, tau PET, and MRI cortical thickness resulted in a small but statistically significant improvement in predicting memory decline over a model with more readily available clinical and genetic variables. The clinical importance of this difference is uncertain.

Cortical ß-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging.

Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical ß-amyloid (Aß) deposition. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging to examine the frequency of NPS among cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants who either have normal (A-) or abnormal (A+) Aß deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCI/A+) is associated with greater odds of having NPS as compared to CU/A- (defined as reference group). Participants were 1627 CU and MCI individuals aged ≥ 50 years (54% males; median age 73 years). All participants underwent NPS assessment (Neuropsychiatric Inventory Questionnaire (NPI-Q); Beck Depression Inventory II (BDI-II); Beck Anxiety Inventory (BAI)) and 11C-PiB-PET. Participants with an SUVR > 1.42 were classified as A+. We conducted multivariable logistic regression analyses adjusted for age, sex, education, and APOE ε4 genotype status. The sample included 997 CU/A-, 446 CU/A+, 78 MCI/A-, and 106 MCI/A+ persons. For most NPS, the highest frequency of NPS was found in MCI/A+ and the lowest in CU/A-. The odds ratios of having NPS, depression (BDI ≥ 13), or anxiety (BAI ≥ 8, ≥ 10) were consistently highest for MCI/A+ participants. In conclusion, MCI with Aß burden of the brain is associated with an increased risk of having NPS as compared to MCI without Aß burden. This implies that the underlying Alzheimer's disease biology (i.e., cerebral Aß amyloidosis) may drive both cognitive and psychiatric symptoms.

Factors Associated With Meningioma Detected in a Population-Based Sample.

OBJECTIVE: To determine the frequency of incidental meningioma and identify associated factors in a population-based sample of participants who systematically underwent brain imaging. PATIENTS AND METHODS: We searched the Mayo Clinic Study of Aging, a population-based sample of Olmsted County, Minnesota, residents who underwent longitudinal magnetic resonance imaging of the brain. Using a text search of radiologists' notes for 2402 individuals (median age, 75.0 years) who underwent imaging between August 10, 2005, and July 31, 2014, we identified 52 patients (2.2%) who had at least one meningioma. We estimated the association of selected risk factors with the presence of meningioma using odds ratios and 95% CIs from logistic regression models adjusted for age and sex. Based on these results, we moved the most significant variables forward to a multivariable model. RESULTS: Controlling for age and sex, significant associations with the presence of meningioma included higher body mass index (odds ratio [OR], 1.06; 95% CI, 1.01-1.12; P=.03), nonsteroidal anti-inflammatory drugs (OR, 2.11; 95% CI, 1.13-3.95; P=.02), aspirin (OR, 1.90; 95% CI, 1.05-3.46; P=.04), and blood pressure-lowering medication (OR, 2.06; 95% CI, 1.06-3.99; P=.03). Lower risk was associated with male sex (OR, 0.51; 95% CI, 0.29-0.90; P=.02), coronary artery disease (OR, 0.46; 95% CI, 0.22-0.97; P=.04), and higher self-reported anxiety (OR, 0.88; 95% CI, 0.78-0.98; P=.02). Simultaneous adjustment for all of these factors except aspirin in a multivariable model did not attenuate these associations (concordance, 0.71). CONCLUSION: In a population-based sample of 2402 participants, 52 (2.2%) had an incidental meningioma. They were more likely to be female and have higher body mass index. Meningioma was also associated with certain medications (nonsteroidal anti-inflammatory drugs and blood pressure-lowering medications) and inversely with anxiety and coronary artery disease.

Predicting Progression to Mild Cognitive Impairment.

Despite much attention to the use of biomarkers for predicting Alzheimer disease, little information is available at the individual level. We used the population-based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality. For example, a 75-year-old with abnormal amyloid and cortical thinning biomarkers has about a 20% chance of cognitive impairment by age 80 years, whereas with normal biomarkers the chance is <10%. Persons with only one abnormal biomarker had similar intermediate risks. ANN NEUROL 2019;85:155-160.

Cerebral microbleeds: Prevalence and relationship to amyloid burden.

OBJECTIVE: To describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and ß-amyloid burden on PET. METHODS: From the population-based Mayo Clinic Study of Aging, 1,215 participants (53% male) underwent 3-tesla MRI scans with T2* gradient recalled echo sequences from October 2011 to February 2017. A total of 1,123 participants (92%) underwent 11C-Pittsburgh compound B (PiB)-PET scans. The prevalence of CMBs was derived by adjusting for nonparticipation and standardizing to the Olmsted County, MN, population. The relationship between ß-amyloid burden and CMB presence and location was tested using logistic regression models. Ordinal logistic models tested the relationship between CMB frequency and ß-amyloid burden. RESULTS: Two hundred seventy-four participants (22.6%) had at least one CMB. CMB frequency increased with age by decade (11% aged 60-69 years, 22% 70-79 years, and 39% 80 years and older). After adjusting for age, sex, and hypertension, PiB standardized uptake value ratio (SUVR) was associated with increased odds of a CMB. The association between PiB SUVR and CMBs was location-specific; PiB SUVR was associated with lobar CMBs but not deep CMBs. Age, hypertension, and PiB SUVR were associated with increasing CMB count. CMB density was greatest in parietal and occipital regions; ß-amyloid burden correlated with concentration of CMBs in all lobar regions. Among participants with multiple CMBs, greater PiB uptake occurred in the pre- and postcentral gyri superiorly, the superior parietal lobe and precuneus, the angular gyrus, inferior temporal gyrus, and temporal poles. CONCLUSIONS: The prevalence of CMBs increases with age. In this population-based sample, ß-amyloid load was associated with lobar but not with deep CMBs.

Comparison of PC and iPad administrations of the Cogstate Brief Battery in the Mayo Clinic Study of Aging: Assessing cross-modality equivalence of computerized neuropsychological tests.

Objective: Computerized neuropsychological assessments are increasingly used in clinical practice, population studies of cognitive aging and clinical trial enrichment. Subtle, but significant, performance differences have been demonstrated across different modes of test administration and require further investigation. Method: Participants included cognitively unimpaired adults aged 50 and older from the Mayo Clinic Study of Aging who completed the Cogstate Brief Battery and Cogstate's Groton Maze Learning Test (GMLT) on an iPad or a personal computer (PC) in the clinic. Mode of administration differences and test-retest reliability coefficients were examined across 3 cohorts: a demographically matched test-retest cohort completing PC and iPad administrations the same day (N = 168); a test naïve cohort comparing baseline PC (n = 1820) and iPad (n =605) performance; and a demographically matched longitudinal cohort completing 3 Cogstate visits over 15 months on either the PC (n =63) or iPad (n =63). Results: Results showed a small but statistically significant and consistent finding for faster performance on PC relative to iPad for several Cogstate Brief Battery measures. Measures of accuracy generally did not differ or differences were very small. The GMLT showed faster performance and higher total errors on iPad. Most Cogstate variables showed no difference in the rate of change across PC and iPad administrations. Conclusions: There are small, but significant, differences in performance when giving the same cognitive tests on a PC or an iPad. Future studies are needed to better understand if these small differences impact the clinical interpretation of results and research outcomes.

The Association of Multimorbidity With Preclinical AD Stages and SNAP in Cognitively Unimpaired Persons.

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 >1.42) and abnormal (reduced) Alzheimer's disease signature cortical thickness (N+; <2.67 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.

Association of Bilateral Salpingo-Oophorectomy Before Menopause Onset With Medial Temporal Lobe Neurodegeneration.

Importance: There is an increased risk of cognitive impairment or dementia in women who undergo bilateral salpingo-oophorectomy (BSO) before menopause. However, data are lacking on the association of BSO before menopause with imaging biomarkers that indicate medial temporal lobe neurodegeneration and Alzheimer disease pathophysiology. Objective: To investigate medial temporal lobe structure, white matter lesion load, and ß-amyloid deposition in women who underwent BSO before age 50 years and before reaching natural menopause. Design, Setting, and Participants: This nested case-control study of women in the population-based Mayo Clinic Cohort Study of Oophorectomy and Aging-2 (MOA-2) and in the Mayo Clinic Study of Aging (MCSA) in Olmsted County, Minnesota, included women who underwent BSO from 1988 through 2007 and a control group from the intersection of the 2 cohorts. Women who underwent BSO and control participants who underwent a neuropsychological evaluation, magnetic resonance imaging (MRI), and Pittsburgh compound B positron emission tomography (PiB-PET) were included in the analysis. Data analysis was performed from November 2017 to August 2018. Exposure: Bilateral salpingo-oophorectomy in premenopausal women who were younger than 50 years. Main Outcomes and Measures: Cortical ß-amyloid deposition on PiB-PET scan was calculated using the standard uptake value ratio. White matter hyperintensity volume and biomarkers for medial temporal lobe neurodegeneration (eg, amygdala volume, hippocampal volume, and parahippocampal-entorhinal cortical thickness) on structural MRI and entorhinal white matter fractional anisotropy on diffusion tensor MRI were also measured. Results: Forty-one women who underwent BSO and 49 control participants were recruited. One woman was excluded from the BSO group after diagnosis of an ovarian malignant condition, and 6 women were excluded from the control group after undergoing BSO after enrollment. Twenty control participants and 23 women who had undergone BSO completed all examinations. The median (interquartile range [IQR]) age at imaging was 65 (62-68) years in the BSO group and 63 (60-66) years in the control group. Amygdala volume was smaller in the BSO group (median [IQR], 1.74 [1.59-1.91] cm3) than the control group (2.15 [2.05-2.37] cm3; P < .001). The parahippocampal-entorhinal cortex was thinner in the BSO group (median [IQR], 3.91 [3.64-4.00] mm) than the control group (3.97 [3.89-4.28] mm; P = .046). Entorhinal white matter fractional anisotropy was lower in the BSO group (median [IQR], 0.19 [0.18-0.22]) than the control group (0.22 [0.20-0.23]; P = .03). Women were treated with estrogen in both groups (BSO, n = 22 of 23 [96%]; control, n = 10 of 19 [53%]). Global cognitive status test results did not differ between the groups. Conclusions and Relevance: Abrupt hormonal changes associated with BSO in premenopausal women may lead to medial temporal lobe structural abnormalities later in life. Longitudinal evaluation is needed to determine whether cognitive decline follows.

Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia.

OBJECTIVES: To examine the cross-sectional association between functional performance and Alzheimer's disease (AD) neuroimaging biomarkers in individuals without dementia (cognitively unimpaired (CU), and those with mild cognitive impairment (MCI)). DESIGN: Cross-sectional. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Population-based Mayo Clinic Study of Aging (MCSA) participants (aged ≥ 50, mean age 71.3 ± 10.2; 53.4% male; 28.3% apolipoprotein (APO)E ε4 allele carriers, 1,578 CU, 204 MCI) who underwent 11 C-Pittsburgh compound B (11 C-PiB) positron emission tomography (PET) (N=1,782). MEASUREMENTS: We defined an abnormal (high) 11 C-PiB-PET retention ratio as a standardized uptake value ratio greater than 1.42 (high amyloid; A+), abnormal (reduced) AD signature cortical thickness (neurodegeneration; N+) as less than 2.67 mm (MRI measurement), and biomarker groups according to the combination of abnormality (or not) for amyloid accumulation (A+/A-) and neurodegeneration (N+/N-). Functional performance was assessed using the Clinical Dementia Rating (CDR) Sum of Boxes (SOB) for functional domains and the Functional Activities Questionnaire (FAQ). RESULTS: Participants with a CDR-SOB (functional) score greater than 0 were almost 4 times as likely to have N + (odds ratio (OR)=3.92, 95% confidence interval (CI)=1.77-8.67, adjusting for age, sex, education, global cognitive z-score, and APOE ε4 allele status; p<.001) and those with a FAQ score greater than 0 were 1.5 times as likely to have A + (OR=1.48, 95% CI=1.04-2.11, p=.03). Higher FAQ scores were associated with greater odds of A+N + and A-N + in CU participants. CONCLUSION: The findings of this cross-sectional study supplement limited available information that supports an association between functional performance and AD neuroimaging biomarkers very early in the dementia pathophysiology. The associations should be validated in longitudinal studies. J Am Geriatr Soc 66:2274-2281, 2018.

Effect of Cognitive Status on the Receipt of Procedures Requiring Anesthesia and Critical Care Admissions in Older Adults.

OBJECTIVE: To investigate whether older adults with mild cognitive impairment (MCI) or dementia have higher rates of procedures requiring general anesthesia or intensive care unit (ICU) admissions compared with cognitively normal (CN) patients. PATIENTS AND METHODS: A population-based cohort, 70 to 89 years old at enrollment, underwent clinical and longitudinal neurocognitive testing to identify those with MCI and dementia. We analyzed the effects of cognitive status (CN, MCI, or dementia) at entry into the study from October 1, 2004, through December 31, 2014, on the risk of receiving procedures requiring surgical anesthesia and ICU admission. RESULTS: Of 2436 participants, 1977 (81%) were CN, 387 (16%) had MCI, and 72 (3%) had dementia. Cognitively impaired individuals were sicker. Compared with CN individuals, the likelihood of receiving a procedure requiring anesthesia was similar in participants with MCI (adjusted hazard ratio [aHR]=0.98; P=.78). Participants with dementia were less likely to receive these procedures (aHR=0.50; P=.02). Compared with CN participants, the likelihood of ICU admission for any indication was increased for those with MCI (aHR=1.24; P=.03) and dementia (aHR=1.59; P=.04). Admissions to the ICU after procedures were not different in patients with either MCI or dementia (aHR=0.96; P=.83 and aHR=1.01; P=.98, respectively). CONCLUSION: Patients with MCI or dementia are not more likely to undergo surgery, and neither are they more likely to require ICU admission after procedures. An increased rate of nonsurgical ICU admissions requires vigilance to prevent deterioration of nonsurgical diseases that may lead to ICU admissions.

Statins and Brain Health: Alzheimer's Disease and Cerebrovascular Disease Biomarkers in Older Adults.

BACKGROUND: Statins have been proposed to reduce the risk of Alzheimer's disease (AD). OBJECTIVE: Assess whether long-term statin use was associated with neuroimaging biomarkers of aging and dementia. METHODS: Methods: We analyzed neuroimaging biomarkers in 1,160 individuals aged 65+ from the Mayo Clinic Study of Aging, a population-based prospective longitudinal study of cognitive aging. RESULTS: Statin-treated (5+ years of therapy) individuals had greater burden of mid-and late-life cardiovascular disease (p < 0.001) than statin-untreated (≤3 months) individuals. Lower fractional anisotropy in the genu of the corpus callosum, an early marker of cerebrovascular disease, was associated with long-term statin exposure (p < 0.035). No significant associations were identified between long-term statin exposure and cerebral amyloid or tau burden, AD pattern neurodegeneration, or white matter hyperintensity burden. CONCLUSIONS: Long-term statin therapy was not associated with differences in AD biomarkers. Individuals with long-term statin exposure had worse white matter integrity in the genu of the corpus callosum, consistent with the coexistence of higher cerebrovascular risk factor burden in this group.

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.

Mediterranean Diet, Its Components, and Amyloid Imaging Biomarkers.

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 11C-PiB-PET scan measures of amyloid-ß (Aß) 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 Aß 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) ɛ4 allele carrier status, time interval between the FFQ completion and PET scan, and total energy intake. RESULTS: Participants' median age at FFQ was 77.7 years (55.8% men; 26.6% with an APOE ɛ4 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 ß-carotene (beta: -0.039, p = 0.005) from food sources and moderate alcohol consumption (beta: -0.074, p = 0.03) were associated with lower 11C-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 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.

OBJECTIVE: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. METHODS: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. RESULTS: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P < .001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P = .009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P = .014) use were also associated with risk of MCI diagnosis. CONCLUSIONS: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.