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. 2017 Nov;82(5):706-718.
doi: 10.1002/ana.25071. Epub 2017 Oct 26.

Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

Prashanthi Vemuri  1 , Timothy G Lesnick  2 , Scott A Przybelski  2 , David S Knopman  3 , Val J Lowe  1 , Jonathan Graff-Radford  3 , Rosebud O Roberts  2 , Michelle M Mielke  2   3 , Mary M Machulda  4 , Ronald C Petersen  3 , Clifford R Jack Jr  1
Affiliations

Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

Prashanthi Vemuri et al. Ann Neurol. 2017 Nov.

Abstract

Objective: To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample.

Methods: We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC- ) versus CMC > 0 (CMC+ ) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects.

Results: CMC+ participants had significantly greater neurodegeneration than CMC- participants but did not differ by amyloid or ERC-tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC-tau.

Interpretation: Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706-718.

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Conflict of interest statement

Potential Conflicts of Interest

The authors do not any pertinent disclosures relevant to this study.

Figures

Figure 1
Figure 1
Barplots of average vascular risk (CMC variables), amyloid deposition (PIB SUVr), tau deposition (ERC-Tau SUVr), and MRI neurodegeneration (average thickness in AD signature regions in mm) with 95% confidence intervals by 5-year increments.
Figure 2
Figure 2
Final Structural Equation Model along with significant associations shown by solid arrows. The standardized coefficients, standard errors (in brackets), and p-values are shown beside the arrows. The amyloid cascade is shown by the orange boxes. ND denotes neurodegeneration in AD regions on MRI.
Figure 3
Figure 3
Direct and Indirect pathways to (A) vascular health and each of the ADP biomarkers (B) Amyloid; (C) Tau; (D) ND or Neurodegeneration in AD regions on MRI
Figure 4
Figure 4
Final Structural Equation Model with each individual indicator of vascular health along with significant associations shown by solid arrows. The standardized coefficients, standard errors (in brackets), and p-values are shown beside the arrows. The amyloid cascade is shown by the orange boxes. ND denotes neurodegeneration in AD regions on MRI. CHF denotes congestive heart failure.
See this image and copyright information in PMC

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