Knopman, David S.

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 .

Abstract Rationale Growing evidence suggests that compromised lung health may be linked to dementia and worsening cognitive ability. Objectives To test the hypothesis that impaired lung function or lung disease in midlife is associated with greater risk of incident dementia and mild cognitive impairment (MCI) later in life. Methods A total of 14,184 Atherosclerosis Risk in Communities study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. Dementia and MCI were defined by hospitalization diagnosis codes (1987–2013) in the whole cohort and with adjudication among 42% who attended a comprehensive neurocognitive examination (2011–2013). Measurements and Main Results In analysis using adjudicated outcomes, odds of dementia or MCI were higher among participants with restrictive (multivariable-adjusted odds ratio, 1.58; 95% confidence interval, 1.14–2.19) and obstructive lung disease (multivariable-adjusted odds ratio, 1.33; 95% confidence interval, 1.07–1.64), compared with those without disease or respiratory symptoms. Associations were similar in analyses restricted to nonsmokers, and present for both Alzheimer’s disease–related dementia and cerebrovascular etiologies. Low FEV1% predicted and FVC% predicted were also associated with increased dementia risk. Conclusions Midlife lung disease and reduced lung function were associated with modestly increased odds of dementia and MCI later in life. Magnitudes of association were more pronounced for restrictive impairment than for obstructive lung disease. These associations were present in smokers and nonsmokers. If the observed associations are causal, policy and public health efforts to reduce smoking and improve air quality may have the added benefit of preventing the development of dementia and MCI.

AbstractIntroductionThe easily‐imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia.MethodsIn a population‐based study of 12,482 adults aged 50‐73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993‐1995) with incident all‐cause dementia (1993‐1995 to 2011‐2013) and with etiologic subtype of dementia/mild cognitive impairment (2011‐13).ResultsA total of 1259 (10%) participants developed dementia over a mean 15.6 years. Moderate/severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.36–2.55) and central retinal arteriolar equivalent (narrowest quartile vs. widest three quartiles; HR, 1.26; 95% CI: 1.09–1.45) were associated with all‐cause dementia. Results were qualitatively stronger (but not statistically significantly different) in participants with diabetes. Retinopathy was associated with a joint outcome of cerebrovascular‐related, but not Alzheimer's disease–related, dementia/mild cognitive impairment (HR, 2.29; 95% CI: 1.24–4.23).DiscussionExploration of measures in the eye may provide surrogate indices of microvascular lesions relevant to dementia.

Background: Although inflammation has been implicated in the pathogenesis of Alzheimer’s disease, the effects of systemic inflammation on brain amyloid deposition remain unclear. Objective: We examined the association of midlife and late-life systemic inflammation with late-life brain amyloid levels in a community sample of non-demented older adults from the Atherosclerosis Risk in Communities (ARIC) – PET Study. Methods: 339 non-demented participants (age: 75 [SD 5]) were recruited from the ARIC Study to undergo florbetapir PET (amyloid) imaging. Blood levels of high sensitivity C-reactive protein (CRP), a marker of systemic inflammation, were measured 22 years (Visit 2), 16 years (Visit 4), and up to 2 years before PET imaging (Visit 5). Elevated brain amyloid deposition (standardized uptake value ratio >1.2) was the primary outcome. Results: Our primary analyses found no association of midlife and late-life CRP with late-life brain amyloid levels. However, in secondary stratified analyses, we found that higher midlife (Visit 2) CRP was associated with elevated amyloid among males (OR 1.65, 95% CI: 1.13–2.42), and among white (OR 1.33, 95% CI: 1.02–1.75), but not African American, participants ( p-interactions<0.05). Among male participants, those who maintained high CRP levels (≥3 mg/L) throughout mid- and late-life were most likely to have elevated brain amyloid (OR, 8.81; 95% CI: 1.23, 62.91). Conclusions: Although our primary analysis does not support an association between systemic inflammation and brain amyloid deposition, we found evidence for sex- and race-dependent associations. However, findings from subgroup analyses should be interpreted with caution.