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Reduced thalamic volume is associated with early brain pathology in preclinical autosomal dominant Alzheimer’s disease
Author(s) -
PardillaDelgado Enmanuelle,
TorricoTeave Heirangi,
RamirezGomez Liliana A,
Baena Ana,
Bocanegra Yamile,
VilaCastelar Clara,
FoxFuller Joshua T.,
GuzmanVelez Edmarie,
Martínez Jairo,
Sanchez Justin S,
Lopera Francisco,
Quiroz Yakeel T.
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.046347
Subject(s) - brainstem , thalamus , entorhinal cortex , neuroscience , pons , brain size , medicine , psychology , pathology , alzheimer's disease , presenilin , hippocampus , magnetic resonance imaging , disease , radiology
Background Sleep‐wake dysregulation may increase the risk of developing Alzheimer’s Disease (AD). In turn, AD pathology in sleep/wake regulatory brain regions may exacerbate sleep disturbances. It is unclear whether sleep dysregulation occurs before or after the onset of clinical symptoms in AD. In this study, we aimed to investigate whether the volume of brain regions known to regulate sleep/wake cycles (thalamus, brainstem sub‐regions) was different between carriers and non‐carriers of autosomal dominant AD (ADAD); and whether volume of such brain regions is associated with markers of brain pathology (amyloid and tau) and memory performance. Methods A total of 36 non‐demented Presenilin‐1 mutation carriers and 32 age‐matched non‐carrier family members (mean age=36.3, SD=6.1) from the Colombia‐Boston (COLBOS) study underwent memory testing, and MRI and PET scanning. The CERAD word list delayed recall was used to assess memory; FreeSurfer was used to analyze bilateral volumes of the thalamus and sub‐regions of the brainstem (medulla, pons, superior cerebellar peduncle, midbrain); Pittsburgh compound‐B and flortaucipir (FTP) were used to assess cortical amyloid and entorhinal tau levels, respectively. Non‐parametric tests were used to assess group differences and correlations between brain volume, brain pathology, and memory. Results No MRI volumetric differences were found between groups. In carriers, reduced thalamic volume was associated with greater mean cortical amyloid (r= ‐0.48, p=0.006) and entorhinal tau (r= ‐0.46, p=0.008). Reduced thalamic volume was also associated with worse memory performance (r= 0.38, p=0.03). When controlling for age, which is a proxy for clinical progression in this population, these associations were no longer significant. No associations were observed between memory, pathology, and any of the brainstem sub‐regions . Conclusion Findings suggest that brain regions important for sleep‐wake regulation do not show early signs of degeneration in preclinical ADAD. The association between reduced thalamic volume with both cortical amyloid and entorhinal tau supports previous work suggesting that thalamic structures are affected early in the preclinical stage of ADAD. Future research should focus on the functional abnormalities and AD‐related pathology in specific thalamic nuclei during preclinical ADAD, and their potential associations with sleep physiological features, such as thalamic spindles.