Dynamic Amyloid and Metabolic Signatures of Delayed Recall Performance within the Clinical Spectrum of Alzheimer's Disease

Marina Tedeschi Dauar; Tharick Ali Pascoal; Joseph Therriault; Jared Rowley; Sara Mohaddes; Monica Shin; Eduardo R Zimmer; Simon Fristed Eskildsen; Vladimir S Fonov; Serge Gauthier; Judes Poirier; Pedro Rosa-Neto; Alzheimer’s Disease Neuroimaging Initiative

doi:10.3390/brainsci13020232

Dynamic Amyloid and Metabolic Signatures of Delayed Recall Performance within the Clinical Spectrum of Alzheimer's Disease

Brain Sci. 2023 Jan 30;13(2):232. doi: 10.3390/brainsci13020232.

Authors

Marina Tedeschi Dauar^{1

2

3

4}, Tharick Ali Pascoal^{4

5

6}, Joseph Therriault^{4

5

7}, Jared Rowley⁵, Sara Mohaddes⁵, Monica Shin⁵, Eduardo R Zimmer^{5

8}, Simon Fristed Eskildsen⁹, Vladimir S Fonov¹⁰, Serge Gauthier^{4

5}, Judes Poirier^{1

2

4

11}, Pedro Rosa-Neto^{1

4

5

7

12

13}; Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Douglas Mental Health University Institute, 6875 Lasalle Boulevard, Montreal, QC H4H 1R3, Canada.
² Centre for the Studies in the Prevention of Alzheimer's Disease, 6875 Lasalle Boulevard, Montreal, QC H4H 1R3, Canada.
³ CAPES Foundation, Ministry of Education of Brazil, Brasilia 70040-020, DF, Brazil.
⁴ McGill University, Montreal, QC H3A 0G4, Canada.
⁵ Translational Neuroimaging Laboratory, 6825 Lasalle Boulevard, Montreal, QC H4H 1R3, Canada.
⁶ Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, 3811 O'Hara St, Pittsburgh, PA 15213, USA.
⁷ Montreal Neurological Institute, 3801 University st., Montreal, QC H3A 2B4, Canada.
⁸ Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil.
⁹ Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Universitetsbyen 3, 8000 Aarhus, Denmark.
¹⁰ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University St., Montreal, QC H3A 2B4, Canada.
¹¹ Department of Psychiatry, McGill University, Montreal, QC H3A 0G4, Canada.
¹² Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 0G4, Canada.
¹³ The McGill University Research Centre for Studies in Aging 6825 La Salle Boulevard, Montreal, QC H4H 1R3, Canada.

Abstract

Associations between pathophysiological events and cognitive measures provide insights regarding brain networks affected during the clinical progression of Alzheimer's disease (AD). In this study, we assessed patients' scores in two delayed episodic memory tests, and investigated their associations with regional amyloid deposition and brain metabolism across the clinical spectrum of AD. We assessed the clinical, neuropsychological, structural, and positron emission tomography (PET) baseline measures of participants from the Alzheimer's Disease Neuroimaging Initiative. Subjects were classified as cognitively normal (CN), or with early (EMCI) or late (LMCI) mild cognitive impairment, or AD dementia. The memory outcome measures of interest were logical memory 30 min delayed recall (LM30) and Rey Auditory Verbal Learning Test 30 min delayed recall (RAVLT30). Voxel-based [¹⁸F]florbetapir and [¹⁸F]FDG uptake-ratio maps were constructed and correlations between PET images and cognitive scores were calculated. We found that EMCI individuals had LM30 scores negatively correlated with [¹⁸F]florbetapir uptake on the right parieto-occipital region. LMCI individuals had LM30 scores positively associated with left lateral temporal lobe [¹⁸F]FDG uptake, and RAVLT30 scores positively associated with [¹⁸F]FDG uptake in the left parietal lobe and in the right enthorhinal cortex. Additionally, LMCI individuals had LM30 scores negatively correlated with [¹⁸F]florbetapir uptake in the right frontal lobe. For the AD group, [¹⁸F]FDG uptake was positively correlated with LM30 in the left temporal lobe and with RAVLT30 in the right frontal lobe, and [¹⁸F]florbetapir uptake was negatively correlated with LM30 scores in the right parietal and left frontal lobes. The results show that the association between regional brain metabolism and the severity of episodic memory deficits is dependent on the clinical disease stage, suggesting a dynamic relationship between verbal episodic memory deficits, AD pathophysiology, and clinical disease stages.

Keywords: Alzheimer’s disease; FDG-PET; amyloid PET; memory tests; mild cognitive impairment.

Abstract

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