Clinical Symptoms and Symptom Signatures of Alzheimer's Disease Subgroups

Issue title: Tau and Beyond for Alzheimer's Disease: A Special Issue dedicated to Dr. Inge Grundke-Iqbal

Guest editors: Alejandra Alonso and Chengxin Gong

Article type: Research Article

Authors: Iqbal, Khalid^{a; *} | Flory, Michael^b | Soininen, Hilkka^c

Affiliations: [a] Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research In Developmental Disabilities, Staten Island, NY, USA | [b] Research Design and Analysis Service, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA | [c] Department of Neurology, Kuopio University Hospital, Kuopio, Finland

Correspondence: [*] Correspondence to: Khalid Iqbal, Ph.D., Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA. Tel.: +1 718 494 5259; Fax: +1 718 494 1080; E-mail: khalid.iqbal.ibr@gmail.com.

Abstract: Alzheimer's disease (AD) is a multifactorial disorder that involves several different mechanisms. Over 99% of AD patients suffer from the sporadic form of the disease. Based on cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)1-42, total tau, and ubiquitin—the markers associated with the histopathological hallmarks of the disease (Aβ plaques and abnormally hyperphosphorylated neurofibrillary tangles)—previous studies identified five subgroups of AD. Here we report the potential diagnostic predictive value of hallucination, hypokinesia, paranoia, rigidity, and tremors in aged individuals for AD and differences in the prevalence of these symptoms in the CSF marker-based subgroups of the disease. Analysis of 196 clinically diagnosed AD or Alzheimer with Lewy body, and 75 non-AD neurological and non-neurological control cases, all from a single center, showed that the presence of hallucination, hypokinesia, paranoia, rigidity, or tremors individually, or the presence of any of these, could diagnose AD with sensitivities and specificities of 14% and 99%; 30% and 99%; 15% and 99%; 16% and 100%; 16% and 96%; and 47% and 92%, respectively. The pattern of the prevalence of the above symptoms varied from AD subgroup to subgroup. Presence of any of these symptoms, as well as presence of each individual symptom except tremors, significantly differentiated AD subgroups from the predominantly control cluster. These findings encourage the exploration of hallucination, hypokinesia, paranoia, rigidity, and tremors in identifying various subgroups of AD for stratification of patients for clinical trials to develop therapeutic drugs. This study is for the special issue of the Journal of Alzheimer's Disease honoring Inge Grundke-Iqbal who made several seminal contributions in AD research.

Keywords: Alzheimer's disease subgroups, hallucination, hypokinesia, paranoia, rigidity, tremors

DOI: 10.3233/JAD-130899

Journal: Journal of Alzheimer's Disease, vol. 37, no. 3, pp. 475-481, 2013