Increased Hippocampal Blood Flow in Sedentary Older Adults at Genetic Risk for Alzheimer's Disease

Zlatar, Zvinka Z.; Wierenga, Christina E.; Bangen, Katherine J.; Liu, Thomas T.; Jak, Amy J.

doi:10.3233/jad-132252

Cited by 35 publications

(38 citation statements)

References 66 publications

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“…An increase in regional CBF in the preclinical phase of AD when cognitive performance is preserved (as shown in Table ) has been suggested as a compensatory response to the accumulation of Aβ pathology . Other studies also found significant increased perfusion in nondemented elderly subjects at risk for AD, which was also interpreted as a compensatory mechanism leading to a need for extra glucose and oxygen to support neuronal activity . Several functional MRI (fMRI) studies of CN Aβ + also reported increased neural activity during cognitive activity in comparison with young people or CN Aβ– older participants .…”

Section: Discussionsupporting

confidence: 84%

Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease

Fazlollahi

Calamante

Liang

et al. 2019

Magnetic Resonance Imaging

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Background Arterial spin labeling (ASL) is an emerging MRI technique for noninvasive measurement of cerebral blood flow (CBF) that has been used to show hemodynamic changes in the brains of people with Alzheimer's disease (AD). CBF changes have been measured using positron emission tomography (PET) across the AD spectrum, but ASL showed limited success in measuring CBF variations in the preclinical phase of AD, where amyloid β (Aβ) plaques accumulate in the decades prior to symptom onset. Purpose To investigate the relationship between CBF measured by multiphase‐pseudocontinuous‐ASL (MP‐PCASL) and Aβ burden as measured by 11C‐PiB PET imaging in a study of cognitively normal (CN) subjects age over 65. Study Type Cross‐sectional. Population Forty‐six CN subjects including 33 with low levels of Aβ burden and 13 with high levels of Aβ. Field Strength/Sequence 3T/3D MP‐PCASL. Assessment The MP‐PCASL method was chosen because it has a high signal‐to‐noise ratio. Furthermore, the data were analyzed using an efficient processing pipeline consisting of motion correction, ASL motion correction imprecision removal, temporal and spatial filtering, and partial volume effect correction. Statistical Tests General Linear Model. Results In CN subjects positive for Aβ burden (n = 13), we observed a positive correlation between CBF and Aβ burden in the hippocampus, amygdala, caudate (P < 0.01), frontal, temporal, and insula (P < 0.05). Data Conclusion To the best of our knowledge, this is the first study using MP‐PCASL in the study of AD, and the results suggest a potential compensatory hemodynamic mechanism that protects against pathology in the early stages of AD. Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:505–513.

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Section: Discussionsupporting

confidence: 84%

Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease

Fazlollahi

Calamante

Liang

et al. 2019

Magnetic Resonance Imaging

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“…We expect findings will further elucidate the role of vascular dysregulation in AD and support further development of vasoprotective treatments. Given recent findings associating regulatory elevations of CBF in the MTL with sedentary behavior in APOE ε4 carriers [62], and increased CBF in the anterior cingulate following an exercise intervention in older adults [63], future research must exploit the potential disease-modifying role that pharmacological [4] and behavioral lifestyle factors, such as exercise, diet, and cognitive engagement may play in the regulation of CBF and prevention of AD.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow Measured by Arterial Spin Labeling MRI as a Preclinical Marker of Alzheimer's Disease

Wierenga

Hays

Zlatar

2014

JAD

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193

165

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There is growing recognition that cerebral hypoperfusion is related to the pathogenesis of Alzheimer’s disease (AD), implicating the measurement of cerebral blood flow (CBF) as a possible biomarker of AD. The ability to identify the earliest and most reliable markers of incipient cognitive decline and clinical symptoms is critical to develop effective preventive strategies and interventions for AD. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) measures CBF by magnetically labeling arterial water and using it as an endogenous tracer. Studies using ASL MRI in humans indicate that CBF changes are present several years before the development of the clinical symptoms of AD. Moreover, ASL-measured CBF has been shown to distinguish between cognitively normal individuals, adults at risk for AD, and persons diagnosed with AD. Some studies indicate that CBF may even be sensitive for predicting cognitive decline and conversion to mild cognitive impairment and AD over time. Taken together, evidence suggests that the current staging models of AD biomarker pathology should incorporate early changes in CBF as a useful biomarker, possibly present even earlier than amyloid β accumulation. Though still a research tool, ASL imaging is a promising non-invasive and reliable method with the potential to serve as a future clinical tool for the measurement of CBF in preclinical AD.

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“…We recently reported a relationship between sedentary time and CBF that was modified by genetic risk in the left hippocampus, such that APOE ε4 carriers showed higher CBF as a function of longer sedentary time relative to non-carriers. We believe this suggests that sedentary time may act as a behavioral risk factor possibly exacerbating the regulatory increases in CBF usually seen in APOE ε4 carriers (Zlatar et al 2014). Preliminary work currently being collected by our research group suggests that there is a strong positive association between higher sedentary time (measured objectively via accelerometry) and higher levels of CSF tau.…”

Section: Can Behavioral Interventions Modify Cbf To Improve Cognitmentioning

confidence: 92%

The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease

2016

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There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer’s disease (AD), perhaps even before amyloid-β accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease-modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment (MCI) and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease.

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Increased Hippocampal Blood Flow in Sedentary Older Adults at Genetic Risk for Alzheimer's Disease

Cited by 35 publications

References 66 publications

Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease

Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease

Cerebral Blood Flow Measured by Arterial Spin Labeling MRI as a Preclinical Marker of Alzheimer's Disease

The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease

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