Case Report of Complex Amyotrophic Lateral Sclerosis with Cognitive Impairment and Cortical Amyloid Deposition

Article type: Research Article

Authors: Farid, Karim^a | Carter, Stephen F.^{a; f} | Rodriguez-Vieitez, Elena^a | Almkvist, Ove^a | Andersen, Pia^b | Wall, Anders^c | Blennow, Kaj^d | Portelius, Erik^d | Zetterberg, Henrik^{d; e} | Nordberg, Agneta^{a; b; *}

Affiliations: [a] Department NVS, Centre for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden | [b] Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden | [c] Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden | [d] Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden | [e] UCL Institute of Neurology, Queen Square, London, UK | [f] Wolfson Molecular Imaging Cener, University of Manchester, Manchester, United Kingdom

Correspondence: [*] Correspondence to: Agneta Nordberg, MD, PhD, Karolinska Institutet, Department NVS, Centre for Alzheimer Research, Translational Alzheimer Neurobiology, Novum, Blickagången 7, 141 57 Huddinge, Sweden. Tel.: +46 85 858 54 67; Fax: +46 85 858 54 70; agneta.k.nordberg@ki.se

Abstract: Amyotrophic lateral sclerosis (ALS), a fatal disease of unknown origin, affects motor neurons in the primary motor cortex, brainstem, and spinal cord. Cognitive impairment may occur before the motor symptoms. We present a patient who was initially diagnosed with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) but who developed ALS-like symptoms during follow-up and died shortly thereafter. A 60-year-old subject with cognitive impairment underwent neuropsychological testing, cerebrospinal fluid (CSF) analysis, structural imaging (computed tomography and magnetic resonance imaging) and functional imaging [11C]-Pittsburgh compound B (PIB) positron emission tomography (PET), [18F]-fluorodeoxyglucose (FDG) PET, and [11C]-deuterium-L-deprenyl (DED) PET. Neuropsychological testing showed episodic memory impairment. CSF P-tau and T-tau levels were elevated. CSF amyloid-β (Aβ)42 levels were initially normal but became pathological during follow-up. MCI was diagnosed. [18F]-FDG PET showed hypometabolism in the left temporal and prefrontal cortices and [11C]-PIB PET demonstrated amyloid plaque deposition in the prefrontal, posterior cingulate, and parietal cortices. [11C]-DED PET showed high brain accumulation consistent with astrocytosis. The memory impairment progressed and AD was diagnosed. Motor impairments developed subsequently and, following additional neurological evaluation, ALS was diagnosed. The disease progressed rapidly and the patient died with pronounced motor symptoms three years after the initial cognitive assessment. Since relatives refused autopsy, postmortem analysis was not possible.

Keywords: Alzheimer’s disease, amyotrophic lateral sclerosis, [¹¹C]-deprenyl, [¹¹C]-PIB, cerebrospinal fluid biomarkers, [¹⁸F]-FDG, frontotemporal dementia, PET imaging, magnetic resonance imaging

DOI: 10.3233/JAD-141965

Journal: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 661-667, 2015