APOE modifies the interaction of entorhinal cerebral blood flow and cortical thickness on memory function in cognitively normal older adults

Mild traumatic brain injury (mTBI) is a risk factor for Alzheimer’s disease (AD), and evidence suggests cerebrovascular dysregulation initiates deleterious neurodegenerative cascades. We examined whether mTBI history alters cerebral blood flow (CBF) and cortical thickness in regions vulnerable to early AD-related changes. Seventy-four young to middle-aged Veterans (mean age = 34, range = 23–48) underwent brain scans. Participants were divided into: (1) Veteran Controls ( n = 27), (2) 1–2 mTBIs ( n = 26), and (2) 3+ mTBIs ( n = 21) groups. Resting CBF was measured using MP-PCASL. T1 structural scans were processed with FreeSurfer. CBF and cortical thickness estimates were extracted from nine AD-vulnerable regions. Regression analyses examined whether mTBI moderated the association between age, CBF, and cortical thickness. Regressions adjusting for sex and posttraumatic stress revealed mTBI moderated the association between age and CBF of the precuneus as well as superior and inferior parietal cortices ( p’s < .05); increasing age was associated with lower CBF in the 3+ mTBIs group, but not in the VCs or 1–2 mTBIs groups. mTBI did not moderate associations between age and cortical thickness ( p’s >.05). Repetitive mTBI is associated with cerebrovascular dysfunction in AD-vulnerable regions and may accelerate pathological aging trajectories.

Download Full-text

Increasing cerebral blood flow improves cognition into late stages in Alzheimer’s disease mice

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19873658 ◽

2019 ◽

Vol 40 (7) ◽

pp. 1441-1452 ◽

Cited By ~ 4

Author(s):

Oliver Bracko ◽

Brendah N Njiru ◽

Madisen Swallow ◽

Muhammad Ali ◽

Mohammad Haft-Javaherian ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Short Term Memory ◽

Memory Function ◽

Neutrophil Adhesion ◽

Short Term ◽

Term Memory ◽

Model Of Alzheimer’S Disease

Alzheimer’s disease is associated with a 20–30% reduction in cerebral blood flow. In the APP/PS1 mouse model of Alzheimer’s disease, inhibiting neutrophil adhesion using an antibody against the neutrophil specific protein Ly6G was recently shown to drive rapid improvements in cerebral blood flow that was accompanied by an improvement in performance on short-term memory tasks. Here, in a longitudinal aging study, we assessed how far into disease development a single injection of anti-Ly6G treatment can acutely improve short-term memory function. We found that APP/PS1 mice as old as 15–16 months had improved performance on the object replacement and Y-maze tests of spatial and working short-term memory, measured at one day after anti-Ly6G treatment. APP/PS1 mice at 17–18 months of age or older did not show acute improvements in cognitive performance, although we did find that capillary stalls were still reduced and cerebral blood flow was still increased by 17% in 21–22-months-old APP/PS1 mice given anti-Ly6G antibody. These data add to the growing body of evidence suggesting that cerebral blood flow reductions are an important contributing factor to the cognitive dysfunction associated with neurodegenerative disease. Thus, interfering with neutrophil adhesion could be a new therapeutic approach for Alzheimer’s disease.

Download Full-text