Associations between subregional thalamic volume and brain pathology in autosomal dominant Alzheimer’s disease

Abstract

Histopathological reports suggest that subregions of the thalamus, which regulates multiple physiological and cognitive processes, are not uniformly affected by Alzheimer’s disease. Despite this, structural neuroimaging studies often consider the thalamus as a single region. Identification of in vivo Alzheimer’s-dependent volumetric changes in thalamic subregions may aid the characterization of early nuclei-specific neurodegeneration in Alzheimer’s disease. Here, we leveraged access to the largest single-mutation cohort of autosomal-dominant Alzheimer’s disease to test whether cross-sectional abnormalities in subregional thalamic volumes are evident in non-demented mutation carriers (n = 31), compared to non-carriers (n = 36), and whether subregional thalamic volume is associated with age, markers of brain pathology, and cognitive performance. Using automatic parcellation we examined the thalamus in six subregions (anterior, lateral, ventral, intralaminar, medial, posterior) and their relation to age and brain pathology (amyloid and tau), as measured by PET imaging. No between-group differences were observed in the volume of the thalamic subregions. In carriers, lower volume in the medial subregion was related to increased cortical amyloid and entorhinal tau burden. These findings suggest that thalamic Alzheimer’s-related volumetric reductions are not uniform even in preclinical and prodromal stages of autosomal-dominant Alzheimer’s disease and therefore, this structure should not be considered as a single, unitary structure in Alzheimer’s disease research.

Vascular-water-exchange MRI (VEXI) enables the detection of subtle BBB breakdown in Alzheimer’s disease without MRI contrast agent

“…Evidence reveals that lesions to higher-order thalamic areas, such as the pulvinar and mediodorsal nucleus, can produce severe attention and memory deficits (Baxter, 2013; Bradfield et al, 2013), suggesting an important role for the thalamus in cognition. Recent studies have also shown the atrophy of thalamus in AD, which has also been proven in this study, and its potential role in the cognitive dysfunction (De Jong et al, 2008; Pardilla-Delgado et al, 2021).…”

A structural and resting‐state functional connectivity investigation of the pulvinar in elderly individuals and Alzheimer's disease patients

“…The connectivity of the pulvinar in non‐human primates has been well described with its diverse connections with cortical and subcortical regions. These non‐human neuroanatomical studies reported that the pulvinar is interconnected with the prefrontal cortex, posterior cingulate cortex, inferior temporal gyrus, inferior parietal lobule, insular cortex, visual cortical areas, amygdala, superior colliculus, pons, and putamen, highlighting the role of the pulvinar as a multimodal integration center 23,26,37 . In our study the general connectivity pattern is consistent with studies shown in monkeys and our rs‐fMRI data represent a considerable fraction shown in the previous monkey studies.…”

“…7,16,18 Although global differences were observed in AD-related GM volumes, the pulvinar region remained significantly affected in AD dementia at the < 0.01 level. Based on the previous literature suggesting that thalamic AD-related volumetric reductions are not uniform, 36 we have obtained age-corrected values. Additionally, we performed correlation analysis between ages and imaging results (time series) separately in the control and AD groups.…”

Going round in circles—The Papez circuit in Alzheimer's disease

“…A substantial amount of evidence has also shown thalamic changes in ADAD. For instance, reduced thalamic volumes, increased fractional anisotropy and increased mean diffusivity have been described in PMC and SMC PSEN1 carriers (Pardilla‐Delgado et al, 2021; Ryan et al, 2013; Sala‐Llonch et al, 2015), changes that have been described, even 15 years prior to symptom onset (Lee et al, 2013). Furthermore, the thalamus has been described as one of the earliest sites of amyloid deposition (Knight, Okello, et al, 2011).…”