Alteration of perivascular spaces in early cognitive decline: Neuroimaging / Optimal neuroimaging measures for early detection. (7th December 2020) - Sepehrband, Farshid
Abstract: Background: Vascular contributions to early cognitive decline are increasingly recognized, prompting further investigation into the nature of related changes in perivascular space (PVS). Here we investigated the association between PVS volume fraction and early cognitive decline, neurofibrillary tau and Amyloid‐b uptake and APOE status. Method: Data were obtained from the ADNI‐3 database. A total of 685 participants with magnetic resonance imaging (MRI) data were assessed, and 596 participants (326 female [54.6%]) with complete data that passed quality control and inclusion criteria were included (cognitively normal participants age: 73.04 ± 7.36; mild cognitive impairment participants age = 75.56 ± 8.16). PVS volume fraction and brain volume were estimated from MRI using an automated in‐house pipeline; Amyloid‐b and Tau status were determined from PET images and CSF samples; Demographic, cognitive information and cardiovascular risk factors were also collected. Cognitive assessment scores were used to categorized individuals into cognitively normal and mild cognitive impairment subjects. Analysis models were adjusted for age, sex and years of educations. Result: A significantly lower PVS volume fraction in mild cognitive impairment was observed compared to the cognitively normal group in both left ( p =0.00047) and right ( p =0.0009) anterosuperior medial temporal lobe (Figure 1). PVS volume fraction of the centrum semi‐ovale of the white matter was higher in mild cognitive impairment compared to cognitively normal participants, but not statistically significant after adjusting for age, sex, education and brain volume ( p =0.07). PVS volume fraction in anterosuperior medial temporal lobe was significantly associated with Tau PET standardized uptake value ratio in right entorhinal cortex (beta (SE) = ‐0.02 (0.007); p =0.006). PVS volume fractions across different regions were independent of Amyloid load or APOE e4 status. Conclusion: We show that, compared to a cognitively normal sample, individuals with early cognitive dysfunction have altered PVS presence and distribution, irrespective of Amyloid‐b. Surprisingly, we noted decreased PVS presence in the anterosuperior medial temporal lobe, which was associated with neurofibrillary tau tangle deposition in the entorhinal cortex, one of the hallmarks of early Alzheimer's disease pathology. Our results suggest that anatomically‐specific alteration of the PVS may provide an early biomarker of cognitive impairment in aging adults.