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O5‐01‐02: Stress is Associated with Greater Insulin Resistance, Higher CSF Phosphorylated TAU, and Decreased Glucose Metabolism in the Medial Temporal Lobe in apoe Ε4 Carriers
Author(s) -
Hoscheidt Siobhan M.,
Nicholas Christopher R.,
Ly Martina,
Zetterberg Henrik,
Blennow Kaj,
Krause Rachel A.,
Gleason Carey E.,
Atwood Craig S.,
Carlsson Cynthia M.,
Rowley Howard A.,
Asthana Sanjay,
Johnson Sterling C.,
Bendlin Barbara B.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.706
Subject(s) - insulin resistance , apolipoprotein e , medicine , insulin , endocrinology , homeostatic model assessment , cerebrospinal fluid , carbohydrate metabolism , dementia , risk factor , asymptomatic , homeostasis , oncology , disease
labeling (ASL) MRI is decreased in patients with AD (Gao et al. 2013). In this study, ASL measurements with a breath-hold paradigm were used to assess cerebrovascular reactivity and thus vascular injury in normal and cognitively impaired older adults that may be associated with AD pathological processes. Methods: 113 subjects (75 cognitively normal, 34 MCI, and 4 AD; 37M/ 76F; age: 64.667.6) underwent baseline brain MRI as part of several on-going studies of AD prevention and treatment, including ASL at rest and during a 20 second breath-hold with full brain coverage using a 3T Siemens scanner. For the majority of participants, Mini-Mental Status Exam (MMSE) scores and apolipoprotein E (APOE) genotype were available, and for a subset, CSF was collected and amyloid-beta 42 (Ab42) and tau protein levels were measured. Cerebral blood flow (CBF) was quantified from the ASL images. Voxel-wise percent difference maps between baseline and breath-hold CBF were computed and the gray matter (GM) voxels were averaged over the whole brain (see Figure 1 for representative CBF maps). Relationships between breath-hold related changes in CBF and APOE, CSF biomarker levels, and MMSE were examined using regression analyses. Results:Average percent change in GM CBF during a breath-hold paradigm was positively correlated with CSF levels of Ab42 (P1⁄40.025; Figure 2). Decreased CSF measurements of Ab42 peptide are hypothesized to reflect increased Ab plaques in the brain (Blennow, 2004). Thus in our study, increased vascular reactivity is associated with a healthier CSFAb42 profile, likely reflecting less AD pathology. Among subjects with the ε4 allelic variant of the APOE genotype, percent change in GM CBF positively correlated with MMSE (P1⁄40.05), indicating decreased global cognitive function may be associated with cerebrovascular damage. The results of all regression analyses are provided in Table 1.Conclusions:Our findings suggest that brain levels of Ab42 may predict cerebral vascular reactivity in APOE ε4 allele carriers, and this may provide further support for a vascular role in AD risk for these individuals.