Date of Award

January 2019

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Arash Salardini


Memory concerns are common amongst the elderly and need to be thoroughly evaluated since they are often the first presenting symptoms of dementia. However, we hypothesize that amongst patients who present to the neurology clinic with memory disorders, there is a subset of patients with a characteristic clinical phenotype who have a good prognosis and can be managed conservatively. We suggest this clinical phenotype to be called Hyperarousal Amnestic Dys-Executive Syndrome (HADES). The primary aim for this study is to determine whether a positive risk stratification for HADES at initial presentation is correlated with final diagnosis of HADES, and vice versa. Furthermore, we aim to examine the differences in both bedside and formal neuropsychological testing (when available) for patients who meet or do not meet the proposed diagnostic criteria.

We have previously developed diagnostic criteria for Probable and Possible HADES based on a case series of 34 patients who presented between January and June, 2016. In this study, we performed a retrospective chart review of successive new patients who presented for initial evaluation at the Yale Memory Clinic for memory and related cognitive problems between August 1st, 2016 and July 31st, 2017. We extracted data from the patient charts to evaluate whether the diagnostic criteria for HADES were met, what the diagnostic workup revealed (including bedside neuropsychological testing, formal neuropsychological testing, imaging results, biomarker results, and other pertinent laboratory values), and what the final diagnosis for each patient was.

A total of 172 patients were eligible for risk stratification. Forty-five patients (26.2%) were stratified as Probable HADES, a further 25 patients (14.5%) were stratified as a subtype of Possible HADES, and 102 patients (59.3%) were stratified as Negative HADES. A total of 139 patients had a valid final diagnosis; 32 patients had a final tentative diagnosis of HADES, and 107 had a non-HADES diagnosis. Of patients diagnosed with Probable HADES, 23/24 (95.8%) had a final diagnosis of HADES. Of patients stratified with Possible HADES with visuospatial deficits, 0/3 (0%) had a final diagnosis of HADES, while 9/13 (69.2%) patients stratified as Possible HADES with speed of mentation changes were diagnosed with HADES. No patients stratified as Negative HADES received a final diagnosis of HADES. Patients who were stratified as Probable HADES had a higher mean age and greater mean total Montreal Cognitive Assessment (MoCA) score compared to Negative HADES, whereas patients stratified as Possible HADES had an intermediate age and MoCA score. Neuropsychological testing was highly heterogeneous amongst patients and could not be interpreted reliably.

Overall, this retrospective chart review provides initial evidence that a majority of patients who meet the diagnostic criteria for HADES did not have evidence of a primary dementia syndrome. The HADES-stratified patients also had clinical characteristics that were distinct from patients who did not meet the diagnostic criteria. Future research should be aimed at providing further evidence for the syndrome with prospective testing, given the limitations of this retrospective review.


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