Arnaud Valladier, France
ICM Institut du CerveauAuthor Of 1 Presentation
TIMING AND ORDER OF PATHOLOGICAL EVENTS IN ALZHEIMER'S DISEASE: FOCUS ON THE TRAJECTORY OF THE AWARENESS OF COGNITIVE DECLINE
Abstract
Aims
We built an Alzheimer’s disease (AD) Course Map depicting the timing and order of the pathological events occurring during AD progression, with a particular focus on the evolution of the awareness of cognitive decline (ACD).
Methods
We included 373 ADNI participants with positive markers of amyloid and tau (A+T+), and 145 A-T- cognitively-normal controls.
The AD Course Map was built by including measures of global cognition (MMSE), episodic memory (RAVLT), autonomy (FAQ), self- and informant-reported ratings of cognitive functioning (E-Cog), brain metabolism, hippocampal volume. An Awareness of Cognitive Decline Index (ACDI) was computed as the subject-informant discrepancy in the E-Cog score. All measures were normalized between 0 (normal) and 1 (abnormal). We used a non-linear Bayesian mixed-effects model in the Leaspy software (https://gitlab.com/icm-institute/aramislab/leaspy/).
Results
Our model identified the following temporal sequence of events in AD (see Figure): the episodic memory was the first measure to become abnormal in A+T+ subjects (i.e. different from controls), followed by autonomy, study-partner’s E-Cog score, brain metabolism and MMSE, hippocampal volume, and finally subject’s E-Cog score (this letter occurring around 3 years after the diagnosis of dementia).
The ACDI had a non-linear evolution: the subject initially experiences cognitive complaints but his/her ACD soon decreases, eventually constituting a clear anosognosia.
Conclusions
The study of ACD in AD is a piece of the larger understanding of the pre-dementia phases. The presence of an informant is useful to identify the first signs of the disease and anticipate the diagnosis.