Low Amygdala Volumes Present in Early Stages of Alzheimer Disease

Lower amygdala volumes are present during the earliest stages of Alzheimer disease and worsen with increased disease severity.

In patients with early stages of Alzheimer disease (AD), low amygdala volumes are observed that worsen with increased disease severity, according to study results presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held from April 22 to 27, in Boston, Massachusetts.

Amygdala atrophy in the earliest AD stages, including in the preclinical period, remains to be elucidated, with amygdala proposed as a potential early target of AD pathology. Recognizing that neuropsychiatric symptoms represent a common early presentation of AD, researchers sought to explore whether structural changes in the amygdala arise during the earliest stages of disease.

The current retrospective, cross-sectional study comprised participants from the Alzheimer’s Disease Neuroimaging Initiative with the following characteristics:

  • Age ≥50 years
  • Availability of 3D T-1 weighted magnetic resonance imaging scans
  • Presence of cerebrospinal fluid (CSF) biomarkers of AD

Individuals who were considered “cognitively normal” were those with a Clinical Dementia Rating of 0. Participants’ AD pathology was considered “positive” according to previously determined CSF criteria.

[A]mygdala volumes were associated with CSF AD biomarkers and neuropsychiatric symptoms.

A total of 466 participants fulfilled all of the study criteria, which were as follows:

  • 112 cognitively normal individuals with negative CSF biomarkers (CN)
  • 38 individuals with preclinical AD (PAD)
  • 106 individuals with early mild cognitive impairment (EMCI)
  • 100 individuals with late mild cognitive impairment (LMCI)
  • 110 individuals with AD dementia

The researchers found that in patients who had worsening disease severity, amygdala volumes were significantly lower, as seen with this schematic of disease progression (CN > PAD > EMCI > LMCI > AD dementia; P <.001). Further, volume of amygdala was significantly associated with levels of CSF amyloid-beta 42 (β, 0.28653) total tau (β, –0.8881), and phosphorylated tau 181 (β, –7.558; P <.001 for all).

Additionally, Neuropsychiatric Inventory (NPI) disinhibition and aberrant motor behavior scores were negatively associated with amygdala volume (ie, NPI disinhibition [β, –28.556] and NPI aberrant motor behavior scores [β, –57.427]; P <.05 for both).

“[A]mygdala volumes were associated with CSF AD biomarkers and neuropsychiatric symptoms,” the researchers noted. “These findings support amygdala atrophy as an early target of AD pathology,” they concluded.


Al-Ani L, Tao A, Dyke J, Cheng G, Ishii M. Amygdala atrophy as an early manifestation of Alzheimer’s disease. Abstract presented at: 2023 AAN Annual Meeting; April 22-27, 2023; Boston, MA. Abstract S39.006.