Changes in the language system as amyloid-β accumulates

Abstract

Language dysfunction is common in Alzheimer’s disease. There is increasing interest in the preclinical or asymptomatic phase of Alzheimer’s disease. Here we examined in 35 cognitively intact older adults (age range 52–78 years at baseline, 17 male) in a longitudinal study design the association between accumulation of amyloid over a five to six year period, measured using PET, and functional changes in the language network measured over the same time period using task-related functional MRI. In the same participants, we also determined the association between the longitudinal functional MRI changes and a cross-sectional measure of tau load as measured with 18F-AV1451 PET. As predicted, the principal change occurred in posterior temporal cortex: In the cortex surrounding the right superior temporal sulcus, the response amplitude during the associative-semantic versus visuoperceptual task increased over time as amyloid load accumulated (Pcorrected = 0.008). In a whole-brain voxelwise analysis, amyloid accumulation was also associated with a decrease in response amplitude in the left inferior frontal sulcus (Pcorrected = 0.009) and the right dorsomedial prefrontal cortex (Pcorrected = 0.005). In cognitively intact older adults, cross-sectional tau load was not associated with longitudinal changes in fMRI response amplitude. Our findings confirm the central role of the neocortex surrounding the posterior superior temporal sulcus as the area of predilection within the language network in the earliest stages of Alzheimer’s disease. Amyloid accumulation has an impact on cognitive brain circuitry in the asymptomatic phase of Alzheimer’s disease.

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s disease

“…This was defined as AAL 91–108 and was masked by the participant-specific GM map (GM threshold >0.3). SUVRs were then converted to Centiloids ( Klunk et al., 2015 ) using the formulas CL Flut = 127.6 × SUVR -149, CL PiB = 132.53 × SUVR – 174.64 ( De Meyer et al., 2020 ; Reinartz et al., 2021 ). Individuals were included in the analysis with following criteria: baseline CL < 23.5 for all individuals, CL < 23.5 at follow-up (T1) for the control group, CL ≥ 23.5 at T1 for amyloid accumulators.…”

Category Switching Test: A Brief Amyloid-β-Sensitive Assessment Tool for Mild Cognitive Impairment

“…Some semantic deficits involving verbal fluency are attributable to executive dysfunction and are also associated with the connection between the frontal and temporal lobes, which are the main components of the semantic network (Sumner et al, 2018). In cognitively intact older adults, Ab is associated with the declining local function of the temporal and frontal lobes (Reinartz et al, 2021) and the disconnection between mesial temporal and other brain regions (Mueller & Weiner, 2017). In our study, some impaired FCs between the frontal and temporal lobes were associated with CaST, but not AV45 SUVR, suggesting that these impaired FCs may involve other mechanisms, such as tau (Tideman et al, 2022) or neuroinflammation (Passamonti et al, 2019).…”

Phospho‐specific plasma p‐tau181 assay detects clinical as well as asymptomatic Alzheimer's disease

“…For both tracers, a composite SUVR was calculated in a volume of interest involving five bilateral cortical areas (frontal, parietal, anterior cingulate, precuneus‐posterior cingulate and lateral temporal) derived from the Automated Anatomical Labelling atlas and intersected with participant‐specific grey matter thresholded at 0.3 21 . Aβ‐PET measurements were harmonised across tracers through conversion of SUVR values to Centiloids using our previously validated analysis pipeline 22–24 . Individuals were considered to be Aβ‐positive when Centiloids > 23.5, thus identifying Thal phase 3‐to‐5 25 .…”

“… 21 Aβ‐PET measurements were harmonised across tracers through conversion of SUVR values to Centiloids using our previously validated analysis pipeline. 22 , 23 , 24 Individuals were considered to be Aβ‐positive when Centiloids > 23.5, thus identifying Thal phase 3‐to‐5. 25 For voxelwise analyses, Centiloid maps were constructed by applying the conversion formula to each voxel of the SUVR image followed by smoothing with an isotropic 3D Gaussian kernel at 8 mm full width at half maximum.…”