Tse, Nga Yan;
Bocchetta, Martina;
Todd, Emily G;
Devenney, Emma M;
Tu, Sicong;
Caga, Jashelle;
Hodges, John R;
... Ahmed, Rebekah M; + view all
(2023)
Distinct hypothalamic involvement in the amyotrophic lateral sclerosis-frontotemporal dementia spectrum.
NeuroImage: Clinical
, 37
, Article 103281. 10.1016/j.nicl.2022.103281.
(In press).
Preview |
Text
Bochetta_1-s2.0-S2213158222003461-main.pdf Download (1MB) | Preview |
Abstract
Background: Hypothalamic dysregulation plays an established role in eating abnormalities in behavioural variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS). Its contribution to cognitive and behavioural impairments, however, remains unexplored. Methods: Correlation between hypothalamic subregion atrophy and cognitive and behavioural impairments was examined in a large sample of 211 participants (52 pure ALS, 42 mixed ALS-FTD, 59 bvFTD, and 58 age- and education- matched healthy controls). Results: Graded variation in hypothalamic involvement but relative sparing of the inferior tuberal region was evident across all patient groups. Bilateral anterior inferior, anterior superior, and posterior hypothalamic subregions were selectively implicated in memory, fluency and processing speed impairments in addition to apathy and abnormal eating habits, taking into account disease duration, age, sex, total intracranial volume, and acquisition parameters (all p ≤ .001). Conclusions: These findings revealed that subdivisions of the hypothalamus are differentially affected in the ALSFTD spectrum and contribute to canonical cognitive and behavioural disturbances beyond eating abnormalities. The anterior superior and superior tuberal subregions containing the paraventricular nucleus (housing oxytocinproducing neurons) displayed the greatest volume loss in bvFTD and ALS-FTD, and ALS, respectively. Importantly, the inferior tuberal subregion housing the arcuate nucleus (containing different groups of neuroendocrine neurons) was selectively preserved across the ALS-FTD spectrum, supporting pathophysiological findings of discrete neuropeptide expression abnormalities that may underlie the pathogenesis of autonomic and metabolic abnormalities and potentially certain cognitive and behavioural symptom manifestations, representing avenues for more refined symptomatic treatment targets.
| Type: | Article |
|---|---|
| Title: | Distinct hypothalamic involvement in the amyotrophic lateral sclerosis-frontotemporal dementia spectrum |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nicl.2022.103281 |
| Publisher version: | https://doi.org/10.1016/j.nicl.2022.103281 |
| Language: | English |
| Additional information: | © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/). |
| Keywords: | Frontotemporal dementia Amyotrophic lateral sclerosis Hypothalamus Neuroimaging Neuropathophysiology Cognitive and behavioural impairment |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10161620 |
Archive Staff Only
 |
View Item |
