Forget About Memory: Disentangling the Amnestic Syndrome in Idiopathic Normal Pressure Hydrocephalus

Article type: Research Article

Authors: Lingenberg, Alma^{a; b; *} | Herrmann, François R.^{b; c} | Armand, Stéphane^d | Péron, Julie^e | Assal, Frédéric^a | Allali, Gilles^{f; g}

Affiliations: [a] Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals, Geneva, Switzerland | [b] Faculty of Medicine, University of Geneva, Geneva, Switzerland | [c] Department of Rehabilitation and Geriatrics, Division of Geriatrics, Geneva University Hospitals, Geneva, Switzerland | [d] Kinesiology Laboratory, Geneva University Hospitals and University of Geneva, Geneva, Switzerland | [e] Clinical and Experimental Neuropsychology Laboratory, Department of Psychology and Educational Sciences, University of Geneva, Switzerland | [f] Leenaards Memory Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland | [g] Department of Neurology, Division of Cognitive and Motor Aging, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA

Correspondence: [*] Correspondence to: Alma Lingenberg, Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals, rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland. E-mail: alma.lingenberg@hug.ch.

Abstract: Background:Idiopathic normal pressure hydrocephalus (iNPH) can present with both episodic amnestic syndrome and biomarkers of Alzheimer’s disease (AD) pathology. Objective:To examine the associations between amnestic syndrome and cerebrospinal fluid (CSF) AD biomarkers in iNPH and the CSF tap test response in iNPH patients with amnestic syndrome. Methods:We used the Free and Cued Selective Reminding Test to divide iNPH into amnestic and non-amnestic patients. We compared their clinical, biological, and radiological characteristics and examined the reversibility of gait spatiotemporal parameters and neuropsychological performances after a CSF tap test. Univariate and multiple linear regression models examined the association between memory performance and clinical-biological characteristics. 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 AD biomarkers and clinical-radiological profiles. Global cognition and education levels were lower in the amnestic iNPH group. We found no association between AD biomarkers and memory performances (total tau: β= –4.50; 95% CI [–11.96;2.96]; p = 0.236; amyloid-β (1–42): β= 8.60, 95% CI [–6.30;23.50]; p = 0.240). At baseline, amnestic iNPH patients performed worse on executive functions, attention, and gait speed but improved similarly to the non-amnestic iNPH patients after the tap test. Conclusions:In our clinical sample of iNPH patients, we confirm the lack of specificity of the amnestic profile for predicting AD pathology. Clinicians should not preclude amnestic iNPH patients from undergoing an invasive procedure of CSF derivation.

Keywords: Alzheimer’s disease, amyloid protein, cerebrospinal fluid biomarkers, diagnosis, episodic memory, idiopathic normal pressure hydrocephalus, memory deficits, neuropsychology, normal pressure hydrocephalus, tau protein

DOI: 10.3233/JAD-240439

Journal: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1205-1216, 2024