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Mesoscopic compensations for microscopic impairments in mid‐age individuals with family history of dementia
Author(s) -
Su Li
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.042938
Subject(s) - dementia , audiology , family history , voxel , psychology , medicine , neuroscience , disease , radiology
Background In the PREVENT‐dementia study, we investigated multi‐level functional MRI changes in cognitively normal middle‐aged subjects. At the mesoscopic level, regional cerebral hypoperfusion is characteristic of Alzheimer’s disease (AD). At the microscopic level, AD showed a reduced BOLD activity. However, previous studies using these techniques report conflicting findings in cognitively‐normal individuals at high risk of AD. Method 210 subjects between age 40‐59 underwent 3T arterial spin labelling (ASL) MRI and task MRI (tMRI). During the task, subjects made an indoor/outdoor judgment for images of scenes. After a delay of 30‐40 minutes, they identified the stimuli that were previously learnt. As a measurement of stability in neural representations, we quantified the multi‐voxel pattern similarity in parahippocampus regions between the encoding and retrieval parts of the experiment. ASL cerebral perfusion and tMRI responses were statistically compared between subjects with parental history to those without, and carriers of the Apoε4 with non‐carriers. Result Regional hyperperfusion was found in APOE e4 carriers (left cingulate and lateral frontal and parietal regions p<.01) and in those with positive FH (left temporal and parietal regions p<.01). For the tMRI task, we found no overt impairments of memory performance. However, there was a significant change in multivoxel activation pattern in parahippocampus areas for subjects with parental history (p<.01), reflecting a failure to maintain stable memory representations between the learning and testing parts of the experiment. This effect was not seen in the subjects with APOE ε4. Conclusion The novel findings on the implicit memory related MRI task suggest that the microscopic functional impairments may begin as early as mid‐age. The absence of APOE ε4 genotype effect on the task MRI implies that family history may include other genetic and/or environmental risk factors. Hyperperfusion in individuals at increased risk of AD may reflect a nonspecific mesoscopic functional ‘compensation’, offsetting the effects of early neural damages including the reduction in parahippocampus functions.