Sex Differences in the Association Between Midlife Cardiovascular Conditions or Risk Factors With Midlife Cognitive Decline.

BACKGROUND AND OBJECTIVES: The prevalence of midlife cardiovascular conditions and risk factors is higher in men than women. Associations between midlife cardiovascular conditions or risk factors and midlife cognitive decline have been reported, but few studies have assessed sex differences in these associations. METHODS: We included 1,857 participants enrolled in the population-based Mayo Clinic Study of Aging who were 50 to 69 years of age at baseline. Participants were evaluated every 15 months by a coordinator, including neurologic evaluation and neuropsychological testing. The neuropsychological testing used 9 tests to calculate global cognitive and domain-specific (memory, language, executive function, and visuospatial skills) z scores. Nurse abstractors reviewed participant medical records to determine the presence of cardiovascular conditions (coronary heart disease, arrhythmias, congestive heart failure) and risk factors (hypertension, diabetes, dyslipidemia, obesity, ever smoking). Linear mixed-effect models evaluated the association between baseline cardiovascular conditions or risk factors and global and domain-specific cognitive decline. Multivariable models adjusted for demographics, APOE genotype, depression, and other medical conditions. Interactions between sex and each cardiovascular condition or risk factor were examined, and results were stratified by sex. RESULTS: Overall, 1,465 (78.9%) participants had at least 1 cardiovascular condition or risk factor; the proportion of men was higher than women (767 [83.4%] vs 698 [74.5%], p < 0.0001). Cross-sectionally, coronary heart disease and ever smoking were associated with a lower visuospatial z score in multivariable models. Longitudinally, several cardiovascular conditions and risk factors were associated with declines in global and domain-specific z scores but not visuospatial z scores. Most cardiovascular conditions were more strongly associated with cognition among women: coronary heart disease and other cardiovascular conditions were associated with global cognitive decline only in women (all p < 0.05). In addition, diabetes, dyslipidemia, and coronary heart disease were associated with language z score decline only in women (all p < 0.05). However, congestive heart failure was associated with language z score decline only in men (all p < 0.05). DISCUSSION: Midlife cardiovascular conditions and risk factors are associated with midlife cognitive decline. Moreover, specific cardiovascular conditions and risk factors have stronger associations with cognitive decline in midlife for women than men despite the higher prevalence of those conditions in men.

Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities.

INTRODUCTION: Blood-based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect the levels of these markers. METHODS: Plasma markers (Aß42, Aß40, NfL, T-tau, Aß42/40 ratio) were measured on the Quanterix Simoa HD-1 analyzer for 996 Mayo Clinic Study of Aging (MCSA) participants, aged 51 to 95 years. All other data were collected during in-person MCSA visits or abstracted from the medical record. RESULTS: Among cognitively unimpaired (CU) participants, all plasma markers correlated with age. Linear regression models revealed multiple relationships. For example, higher Charlson Comorbidity Index and chronic kidney disease were associated with higher levels of all biomarkers. Some relationships differed between mild cognitive impairment and dementia participants. DISCUSSION: Multiple variables affect plasma biomarkers of amyloid pathology and neurodegeneration among CU in the general population. Incorporating this information is critical for accurate interpretation of the biomarker levels and for the development of reference ranges.

Comparison of variables associated with cerebrospinal fluid neurofilament, total-tau, and neurogranin.

INTRODUCTION: Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total-tau [T-tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging-Alzheimer's Association Research Framework. METHODS: We examined, in a community-based population (N = 777, aged 50-95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays. RESULTS: Multiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status. DISCUSSION: Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.

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.

Weighting and standardization of frequencies to determine prevalence of AD imaging biomarkers.

OBJECTIVE: To estimate the prevalence of elevated brain amyloid and reduced cortical thickness (as a marker for neurodegeneration) in a defined population. METHODS: Mayo Clinic Study of Aging participants underwent MRI to assess a composite Alzheimer disease (AD) signature cortical thickness measure and PET to assess brain amyloid accumulation. Participants were characterized as having elevated amyloid (A+/A-), reduced cortical thickness (N+/N-), and A+N+, A+N-, A-N+, or A-N-. The prevalence of AD biomarkers was derived by adjusting for nonparticipation and standardizing to the Olmsted County, Minnesota, population. RESULTS: Among 1,646 participants without dementia (mean age 70.8 years; 53.2% men), the prevalence (95% confidence interval) of amyloidosis was 21.1% (19.1%-23.2%): women, 24.3%; men, 17.5%. The prevalence of reduced cortical thickness was 28.9% (26.4%-31.5%): women, 27.9%; men, 30.2%. The prevalence estimates of biomarker categories were as follows: A-N-: 61.4%; A+N-: 9.7%; A-N+: 17.4%; and A+N+: 11.5%, and varied by sex and by APOE ε4 carrier status. In men, prevalence estimates were as follows: A-N-: 62.6%; A+N-: 7.3%; A-N+: 19.9%; and A+N+: 10.2%. In women, prevalence estimates were as follows: A-N-: 60.4%; A+N-: 11.7%; A-N+: 15.3%; and A+N+: 12.6%. In ε4 carriers, prevalence estimates were as follows: A-N-: 54.6%; A+N-: 16.6%; A-N+: 12.4%; and A+N+: 16.4%. In non-ε4 carriers, prevalence estimates were as follows: A-N-: 63.3%; A+N-: 6.9%; A-N+: 19.9%; and A+N+: 10.0%. CONCLUSIONS: These prevalence estimates are important for understanding age-related trends in amyloid positivity and AD signature cortical thickness in the population, and for potentially projecting the future burden of biomarkers in elderly persons.