A longitudinal characterization of perfusion in the aging brain and associations with cognition and neural structure

Abstract

Cerebral perfusion declines across the lifespan and is altered in the early stages of several age‐related neuropathologies. Little is known, however, about the longitudinal evolution of perfusion in healthy older adults, particularly when perfusion is quantified using magnetic resonance imaging with arterial spin labeling (ASL). The objective was to characterize longitudinal perfusion in typically aging adults and elucidate associations with cognition and brain structure. Adults who were functionally intact at baseline (n = 161, ages 47–89) underwent ASL imaging to quantify whole‐brain gray matter perfusion; a subset (n = 136) had repeated imaging (average follow‐up: 2.3 years). Neuropsychological testing at each visit was summarized into executive function, memory, and processing speed composites. Global gray matter volume, white matter microstructure (mean diffusivity), and white matter hyperintensities were also quantified. We assessed baseline associations among perfusion, cognition, and brain structure using linear regression, and longitudinal relationships using linear mixed effects models. Greater baseline perfusion, particularly in the left dorsolateral prefrontal cortex and right thalamus, was associated with better executive functions. Greater whole‐brain perfusion loss was associated with worsening brain structure and declining processing speed. This study helps validate noninvasive MRI‐based perfusion imaging and underscores the importance of cerebral blood flow in cognitive aging.

Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease

“…These regions comprise the default mode, dorsal attention and frontoparietal networks associated with attention and executive functions (22). A recent study also found positive associations between the executive function composite score and CBF in dorsolateral prefrontal cortex ( Staffaroni et al, 2019 ). Therefore, it is not surprising that relative CBF in leptoMCA territory was correlated with the executive function composite score.…”

Cortical and Deep Gray Matter Perfusion Associations With Physical and Cognitive Performance in Multiple Sclerosis Patients

“…The importance of sufficient cerebral perfusion in maintaining proper cognitive functioning is recently highlighted in both cross-sectional and longitudinal studies of otherwise cognitively intact healthy population. For an example, a recent 2-year long longitudinal ASL study showed that healthy individuals with decline in GM CBF present with concurrent decline in other markers of brain aging including lower cortical volume, worse WM microstructural integrity, and greater appearance of WM hyperintensities (27). More importantly, the longitudinal GM CBF decline was associated with worsening of the cognitive processing speed (27).…”

“…For an example, a recent 2-year long longitudinal ASL study showed that healthy individuals with decline in GM CBF present with concurrent decline in other markers of brain aging including lower cortical volume, worse WM microstructural integrity, and greater appearance of WM hyperintensities (27). More importantly, the longitudinal GM CBF decline was associated with worsening of the cognitive processing speed (27). Reduction in cerebral perfusion has been also hypothesized as early marker of multiple neurodegenerative diseases, greater cerebral protein accumulation, and as a predictor of dementia development (28).…”

Associations between white matter hyperintensity burden, cerebral blood flow and transit time in small vessel disease: an updated meta-analysis

“…While 2 studies investigated associations between baseline WMH volume and change in either subregional 15 or global 37 CBF, one study considered associations between change in WMH volume and change in cortical grey matter CBF. 36 Fifteen studies used ASL 6-8, 10, 14, 15, 19, 20, 25, 27, 30, 32, 34-36 , 3 used CT perfusion 18,28,29 , 2 used dynamic susceptibility contrast (DSC) MRI 9,37 , one study each used SPECT 21 , phase contrast MRI 22 , CT angiography/digital subtraction angiography, 31 PET, 23 and a combination of CT and DSC MRI 12 . Five studies used transcranial Doppler ultrasound 16,17,24,26,33 .…”

“…Longitudinal analyses of WMH and CBFThe largest of the three new longitudinal studies (Nylander et al 2017)37 in a cohort of 406 randomly selected 75 year old participants at baseline and 252 at follow-up, found no significant association between baseline CBF with WMH progression at a five year follow-up when adjusting for baseline WMH and sex(Table 4). In 136 functionally normal older individuals, Staffaroni et al(2019)36 found that longitudinal reductions in global CBF were associated with increasing WMH burden, adjusting for age, sex and education Promjunyakul et al (2018) 15 ,. in 52 cognitively healthy older participants, found that lower baseline CBF within the PVWMH penumbra was associated with WMH growth at follow-up, while reduced white matter perfusion remained predictive of PVWMH but not DWMH progression, adjusting for age and sex.…”