Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition

Article type: Research Article

Authors: Sala-Llonch, Roser^{a; b; *} | Idland, Ane-Victoria^{a; c} | Borza, Tom^{c; d} | Watne, Leiv Otto^{c; e} | Wyller, Torgeir Bruun^{c; f} | Brækhus, Anne^{f; g; h} | Zetterberg, Henrik^{i; j; k} | Blennow, Kaj^{i; j} | Walhovd, Kristine Beate^a | Fjell, Anders Martin^a

Affiliations: [a] Department of Psychology, Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway | [b] Department of Biomedicine, Faculty of Medicine, University of Barcelona, Barcelona, Spain | [c] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway | [d] Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway | [e] Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway | [f] Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway | [g] Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway | [h] Department of Neurology, Oslo University Hospital, Oslo, Norway | [i] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden | [j] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [k] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK

Correspondence: [*] Correspondence to: Roser Sala-Llonch, PhD, Department of Psychology, Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway. Harald Schjelderups Hus, Forskningsveien 3A, 0373 Oslo, Norway. Tel.: +47 22845129; E-mail: r.s.llonch@psykologi.uio.no.

Abstract: Amyloid deposition occurs in aging, even in individuals free from cognitive symptoms, and is often interpreted as preclinical Alzheimer’s disease (AD) pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD, and hypothesized to interact with amyloid-β (Aβ) in causing cognitive decline early in the cascade of AD pathophysiology. Whether and how Aβ and YKL-40 affect brain and cognitive changes in cognitively healthy older adults is still unknown. We studied 89 participants (mean age: 73.1 years) with cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments from two time-points separated by two years. We tested how baseline levels of Aβ42 and YKL-40 correlated with changes in cortical thickness and cognition. Thickness change correlated with Aβ42 only in Aβ42+ participants (<600 pg/mL, n = 27) in the left motor and premotor cortices. Aβ42 was unrelated to cognitive change. Increased YKL-40 was associated with less preservation of scores on the animal naming test in the total sample (r = –0.28, p = 0.012) and less preservation of a score reflecting global cognitive function for Aβ42+ participants (r = –0.58, p = 0.004). Our results suggest a role for inflammation in brain atrophy and cognitive changes in cognitively normal older adults, which partly depended on Aβ accumulation.

Keywords: Aging, biomarkers, cerebrospinal fluid, cognition, cortical thickness, inflammation, memory, MRI, YKL-40

DOI: 10.3233/JAD-161146

Journal: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 829-840, 2017