Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline

Abstract

<jats:p> Although cerebral blood flow (CBF) alterations are associated with Alzheimer’s disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer’s Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU; n = 80), objectively-defined subtle cognitive decline (Obj-SCD; n = 31), or mild cognitive impairment (MCI; n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants. </jats:p>

Local Functional MR Change Pattern and Its Association With Cognitive Function in Objectively-Defined Subtle Cognitive Decline

“…A 10-year longitudinal study based on the AD Neuroimaging Initiative showed that individuals with Obj-SCD progressed to MCI 2.5-3.4 times faster than the normal group (Thomas et al, 2018). An arterial spin labeling MRI study reported that compared with the normal cognitive function group, the cerebral blood flow of the Obj-SCD participants increased in the hippocampus and inferior parietal; compared with the MCI group, the cerebral blood flow increased in the hippocampus, inferior parietal, and inferior temporal (Thomas et al, 2021). A longitudinal study for 4 years found that Obj-SCD amyloid protein accumulated faster and showed faster thinning of the internal olfactory cortex than the normal group (Thomas et al, 2020).…”

Intrusion errors moderate the relationship between blood glucose and regional cerebral blood flow in cognitively unimpaired older adults

“…We examined the following five a priori ROIs: (1) medial temporal lobe (MTL), which included the hippocampus and entorhinal cortex, (2) precuneus, (3) inferior parietal lobe (IPL), ( 4) medial orbitofrontal cortex (mOFC), and (5) pericalcarine cortex. The first four ROIs were chosen given prior work showing these regions are vulnerable to early AD-related changes and have associations between CBF and AD severity (Bangen et al, 2017;Dickerson et al, 2011;Mattsson et al, 2014;Thomas et al, 2021;Yew & Nation, 2017). The pericalcarine ROI was selected as a control region to examine specificity of any results given that there are no expected changes in AD (Mattsson et al, 2014;Sanchez et al, 2020).…”

“…The pericalcarine ROI was selected as a control region to examine specificity of any results given that there are no expected changes in AD (Mattsson et al, 2014;Sanchez et al, 2020). Consistent with other CBF work in ADNI (Mattsson et al, 2014;Thomas et al, 2021;Yew & Nation, 2017), CBF of the precentral gyrus was selected to serve as a covariate in the models, as it is not thought to be impacted in early AD, allowing for adjustment of expected individual differences in CBF that are likely not due to AD pathologies. If participants were missing baseline ASL data but had ASL data within the first year of their baseline visit, the first occasion of ASL data was used in our analyses.…”

“…Growing evidence suggests that cerebrovascular changes may either accelerate AD-related cognitive decline or be a defining feature of AD (Bangen et al, 2015(Bangen et al, , 2017Lee et al, 2016;Zlokovic, 2011). One indicator of cerebrovascular function is cerebral blood flow (CBF), which has consistently shown a complex relationship with cognitive functioning across the AD continuum such that cognitively unimpaired (CU) individuals at risk for AD may show regional hyperperfusion, while those with frank cognitive impairment show hypoperfusion (Bangen et al, 2012;Fleisher et al, 2009;Mattsson et al, 2014;Thomas et al, 2021;Wierenga et al, 2014).…”

“…Intrusion errors are not considered in calculating the total learning, recall, and recognition scores on traditional word-list measures, and are often overlooked in cohort studies of aging and AD. Recent work has demonstrated that participants with subtle cognitive difficulties, including those with impaired process scores such as intrusion errors, had higher hippocampal CBF than CU or MCI participants (Thomas et al, 2021), such that an inverted-U pattern of regional CBF changes was observed across diagnostic stages.…”