Food and Behaviour Research

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Anxiety symptoms in amnestic mild cognitive impairment are associated with medial temporal atrophy and predict conversion to Alzheimer’s disease

Mah L, Binns MA, Steffens DC,  (2014) The American Journal of Geriatric Psychiatry  DOI: 

Web URL: Read more on the American Journal of Geriatric Psychiatry website here



The purpose of the current study was to test the hypothesis that anxiety in amnestic mild cognitive impairment (aMCI) increases rates of conversion to Alzheimer’s disease (AD), and to identify potential neural mechanisms underlying such an association.


376 participants with aMCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were studied over a median period of 36 months. A Cox proportional-hazards model was used to assess the association between anxiety severity ratings on the Neuropsychiatric Inventory Questionnaire and AD risk. Other variables in the model were depression, memory loss, and MRI-derived AD-related regions-of-interest (ROI), including hippocampal (HC), amygdalar (AMYG), entorhinal cortical (EC) volumes and EC thickness, In addition, a linear regression model was used to determine the effect of anxiety in aMCI on rates of atrophy within ROIs.


Anxiety severity increased rate of a MCI conversion to AD, after controlling for depression and cognitive decline. The association between anxiety and AD remained significant even with inclusion of ROI baseline values or atrophy rates as explanatory variables. Further, anxiety status predicted greater rates of decrease in EC volume. An association between anxiety and EC-thickness missed significance.


Anxiety symptoms in a MCI predict conversion to AD, over and beyond the effects of depression, memory loss, or atrophy within AD neuroimaging biomarkers. These findings, together with the greater EC atrophy rate predicted by anxiety, are compatible with the hypothesis that anxiety is not a prodromal non-cognitive feature of AD, but may accelerate decline towards AD through direct or indirect effects on EC.