Intrinsic Alertness Is Impaired in Patients with Nigrostriatal Degeneration: A Prospective Study with Reference to [¹²³I]FP-CIT SPECT and [¹⁸F]FDG PET

Article type: Research Article

Authors: Frings, Lars^{a; b; *} | Heimbach, Bernhard^a | Meyer, Philipp T.^b | Hellwig, Sabine^{b; c}

Affiliations: [a] Center of Geriatrics and Gerontology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany | [b] Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany | [c] Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany

Correspondence: [*] Correspondence to: Lars Frings, PhD, Center of Geriatrics and Gerontology, Medical Center - University of Freiburg, Faculty of Medicine, Lehener Str. 88, 79106 Freiburg, Germany. Tel.: +49 761 270.70780; Fax: +49 761 270.70890; E-mail: lars.frings@uniklinik-freiburg.de.

Abstract: Background:Variations in alertness and attention are common in Lewy body diseases (LBD) and among the core features of dementia with Lewy bodies (DLB). Dopamine transporter SPECT is an accurate biomarker of nigrostriatal degeneration (NSD) in LBD. Objective:The present study investigated performance on a computerized alertness test as a potential measure of attention in patients with NSD compared to patients without NSD. Methods:Thirty-six patients with cognitive impairment plus at least one core feature of DLB referred for [123I]FP-CIT SPECT imaging were prospectively recruited. Performance in a computerized test of intrinsic alertness was compared between patients with and those without NSD as assessed by [123I]FP-CIT SPECT. Results:Reaction times to auditory stimuli (adjusted for age, sex, and education) were significantly longer in patients with NSD compared to those with a normal [123I]FP-CIT SPECT scan (p < 0.05). Statistical analyses revealed no significant differences comparing reaction times to visual stimuli or dispersion of reaction times between groups. Exploratory analysis in a subgroup of patients with available [18F]FDG PET revealed that longer reaction times were associated with decreased glucose metabolism in the prefrontal cortex (statistical parametric mapping, adjusted for age and sex; p < 0.005, cluster extent > 50 voxels). Conclusion:Computerized assessment of auditory reaction times is able to detect alertness deficits in patients with NSD and might help to measure alertness deficits in patients with LBD and NSD. Future studies in larger samples are needed to evaluate the diagnostic utility of computerized alertness assessment for the differential diagnosis of LBD.

Keywords: Alertness, dementia with Lewy bodies, fluctuations, Lewy body diseases, [¹²³I]FP-CIT SPECT, [¹⁸F]FDG PET

DOI: 10.3233/JAD-191277

Journal: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1721-1729, 2020