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April 13, 2021
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Hypothalamic Atrophy in Alzheimer’s Disease (1819)

April 13, 2021 issue
96 (15_supplement)

Abstract

Objective:

To determine whether structural changes to the hypothalamus are an early feature of Alzheimer’s Disease (AD).

Background:

Non-cognitive symptoms, such as weight loss and sleep disturbances, commonly precede the cognitive decline in AD and are attributable to hypothalamic dysfunction. However, whether hypothalamic atrophy occurs during early stages of AD has not been established.

Design/Methods:

This cross-sectional study included subjects (n=470) from the Alzheimer’s Disease Neuroimaging Initiative aged ≥ 50 years with volumetric T1-weighted MR scans at 3 Tesla and cerebrospinal fluid (CSF) AD biomarkers. Normal cognition (cognitively normal, CN, and preclinical AD) was defined as Clinical Dementia Rating (CDR) of 0. Based on previously established criteria, CN subjects (n=112) were negative for CSF AD pathology, while preclinical AD (n=39), early mild cognitive impairment (EMCI, n=108), late mild cognitive impairment (LMCI, n=100), and AD (n=111) subjects were positive for CSF AD pathology. Average grey matter (GM) densities in the hypothalamus, hippocampus, and cerebellar vermis were assessed by voxel-based morphometry (SPM12 with MarsBaR toolbox).

Results:

Hypothalamic GM densities decreased with increasing clinical severity to a similar degree as the hippocampus with significant differences beginning with EMCI for both regions. Cerebellar vermis GM densities were similar across all groups. Adjusting for age and sex, hypothalamic GM densities were associated with CSF levels of amyloid-β42 (β=0.257, p<0.001) but not with tau or phosphorylated-tau181 (p>0.05). Hippocampal GM densities were associated with all CSF AD biomarkers (p<0.05). Adjusting for age, sex, and education, hypothalamic and hippocampal GM densities were associated with Mini-Mental State Examination (hypothalamus: β=0.360, p<0.001, hippocampus: β=0.512, p<0.001) and CDR Sum of Boxes (hypothalamus: β=−0.441, p<0.001, hippocampus: β=−0.561, p<0.001).

Conclusions:

Evidence for hypothalamic atrophy was found in early stages of AD that worsened with clinical severity in a similar fashion to hippocampal atrophy. These findings support hypothalamic atrophy as an early manifestation of AD.
Disclosure: Ms. Tao has nothing to disclose. Zac Myslinski has nothing to disclose. Ms. Pan has nothing to disclose. Dr. Iadecola has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Broadview Ventures. Jonathan Dyke, 673 has nothing to disclose. Gloria Chiang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Syndax. Gloria Chiang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for medicolegal work. The institution of Gloria Chiang has received research support from NIH/NIA. The institution of Dr. Ishii has received research support from NIH. The institution of Dr. Ishii has received research support from BrightFocus Foundation. The institution of Dr. Ishii has received research support from Alzheimer's Association. Dr. Ishii has received personal compensation in the range of $500-$4,999 for serving as a Author/Contributor with Relias Media.

Information & Authors

Information

Published In

Neurology®
Volume 96Number 15_supplementApril 13, 2021

Publication History

Published online: April 13, 2021
Published in print: April 13, 2021

Authors

Affiliations & Disclosures

Alice Tao
Feil Family Brain and Mind Research Institute
Zachary Myslinski
Feil Family Brain and Mind Research Institute
Yushan Pan
Feil Family Brain and Mind Research Institute
Costantino Iadecola
Feil Family Brain and Mind Research Institute
Department of Neurology
Jonathan Dyke
Department of Radiology, Weill Cornell Medicine
Gloria Chiang
Department of Radiology, Weill Cornell Medicine
Makoto Ishii
Feil Family Brain and Mind Research Institute
Department of Neurology

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