Forget about memory: disentangling the amnestic syndrome in idiopathic Normal Pressure Hydrocephalus.

Background: idiopathic normal pressure hydrocephalus (iNPH) can present with both an episodic amnestic syndrome (or so-called hippocampal profile) and biomarkers of Alzheimer’s pathology. However, it remains unknown if both are related and if an amnestic syndrome accounts for less reversibility after a cerebrospinal fluid derivation. Methods: : we used the Free and Cued Selective Reminding Test to divide iNPH into two groups: the amnestic and non-amnestic patients were compared on their clinical, biological, and radiological characteristics using independent samples t- tests, Chi-Squared or Fisher’s exact tests, as appropriate, as well as the reversibility of gait spatiotemporal parameters and neuropsychological performances before and after a spinal tap test. The association between the memory performances (dependent variable) and the clinical and biological characteristics (independent variables) was examined using univariate and multiple linear regression models. Results: : sixty-two non-amnestic patients (mean age 77.0 ± 7.0 years, 38.7% female) and thirty-eight amnestic patients (mean age 77.0 ± 5.9 years, 36.8% female) presented similar levels of biomarkers for Alzheimer’s disease in the cerebrospinal fluid and clinical-radiological profile. However, global cognition and education levels were lower in the amnestic iNPH. We found no association between Alzheimer’s biomarkers and memory performances (total tau: β = -4.50; 95% CI [-11.96;2.96]; p = 0.236; beta-amyloid (1-42): β = 8.60, 95% CI [-6.30;23.50]; p = 0.240). At baseline, amnestic iNPH performed worse on executive functions, attention, and gait speed but improved similarly to the non-amnestic iNPH after the tap test. Conclusions: : in our clinical sample of iNPH patients, the amnestic syndrome was not related to Alzheimer’s disease pathology, confirming recent studies and the lack of specificity of the amnestic profile for predicting Alzheimer’s pathology. Since amnestic and non-amnestic iNPH patients improve similarly after the tap test, clinicians should not preclude amnestic patients from undergoing an invasive procedure of cerebrospinal fluid derivation.