Relationship Between PET-Assessed Amyloid Burden and Visual and Verbal Episodic Memory Performance in Elderly Subjects

Article type: Research Article

Authors: Squarzoni, Paula^{a; b} | Faria, Daniele de Paula^{b; c} | Yassuda, Mônica Sanches^d | Porto, Fábio Henrique de Gobbi^{b; c} | Coutinho, Artur Martins^{b; c} | Costa, Naomi Antunes da^{a; b} | Nitrini, Ricardo^d | Forlenza, Orestes Vicente^e | Duran, Fabio Luiz de Souza^{a; b} | Brucki, Sonia Maria Dozzi^d | Buchpiguel, Carlos Alberto^{b; c} | Busatto, Geraldo F.^{a; b; *}

Affiliations: [a] Laboratory of Psychiatric Neuroimaging (LIM 21), Departament of Psychiatry, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil | [b] Nucleo de Apoio a Pesquisa em Neurociência Aplicada (NAPNA), Universidade de Sao Paulo, Sao Paulo, SP, Brazil | [c] Laboratory of Nuclear Medicine (LIM 43), Department of Radiology and Oncology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil | [d] Department of Neurology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil | [e] Laboratory of Neuroscience (LIM 27), Departament of Psychiatry, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

Correspondence: [*] Correspondence to: Geraldo Busatto Filho, Centro de Medicina Nuclear do Instituto de Radiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 2° andar, Rua Doutor Ovídio Pires de Campos, 872 - Cerqueira Cesar, São Paulo/SP 05403-911, Brazil. Tel.: +55 11 2661 8132; E-mail: geraldo.busatto@gmail.com; https://orcid.org/0000-0003-4749-4602.

Abstract: Background:Studies of elderly subjects using biomarkers that are proxies for Alzheimer’s disease (AD) pathology have the potential to document meaningful relationships between cognitive performance and biomarker changes along the AD continuum. Objective:To document cognitive performance differences across distinct AD stages using a categorization based on the presence of PET-assessed amyloid-β (Aβ) burden and neurodegeneration. Methods:Patients with mild dementia compatible with AD (n = 38) or amnestic mild cognitive impairment (aMCI; n = 43) and a cognitively unimpaired group (n = 27) underwent PET with Pittsburgh compound-B (PiB) assessing Aβ aggregation (A+) and [18F]FDG-PET assessing neurodegeneration ((N)+). Cognitive performance was assessed with verbal and visual episodic memory tests and the Mini-Mental State Examination. Results:The A+(N)+ subgroup (n = 32) showed decreased (p < 0.001) cognitive test scores compared to both A+(N)–(n = 18) and A–(N)–(n = 49) subjects, who presented highly similar mean cognitive scores. Despite its modest size (n = 9), the A–(N)+ subgroup showed lower (p < 0.043) verbal memory scores relative to A–(N)–subjects, and trend lower (p = 0.096) scores relative to A+(N)–subjects. Continuous Aβ measures (standard uptake value ratios of PiB uptake) were correlated most significantly with visual memory scores both in the overall sample and when analyses were restricted to dementia or (N)+ subjects, but not in non-dementia or (N)–groups. Conclusion:These results demonstrate that significant Aβ-cognition relationships are highly salient at disease stages involving neurodegeneration. The fact that findings relating Aβ burden to memory performance were detected only at (N)+ stages, together with the similarity of test scores between A+(N)–and A–(N)–subjects, reinforce the view that Aβ-cognition relationships during early AD stages may remain undetectable unless substantially large samples are evaluated.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, cognition, cognitively unimpaired, 18-fluorode oxyglucose positron emission tomographic, Pittsburgh compound-B

DOI: 10.3233/JAD-200758

Journal: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 229-244, 2020