Tracking the progression of Alzheimer's disease: Insights from metabolic patterns of SOMI stages

Andrea Brugnolo; Beatrice Orso; Nicola Girtler; Pilar Maria Ferraro; Dario Arnaldi; Pietro Mattioli; Federico Massa; Francesco Famà; Lucia Argenti; Gabriella Biffa; Wanda Morganti; Silvia Buonopane; Antonio Uccelli; Silvia Morbelli; Matteo Pardini

doi:10.1016/j.cortex.2023.11.011

Tracking the progression of Alzheimer's disease: Insights from metabolic patterns of SOMI stages

Cortex. 2024 Feb:171:413-422. doi: 10.1016/j.cortex.2023.11.011. Epub 2023 Nov 30.

Authors

Affiliations

¹ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Clinical Psychology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: Andrea.Brugnolo@unige.it.
² Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy. Electronic address: beatrice27orso@gmail.com.
³ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Clinical Psychology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: nicolagirtler@unige.it.
⁴ Department of Neurology, IRCCS Policlinico San Martino, Genova, Italy. Electronic address: pilarmariaferraro@gmail.com.
⁵ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: dario.arnaldi@gmail.com.
⁶ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: mattioli.pietro092@gmail.com.
⁷ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: fedemassa88@gmail.com.
⁸ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: francesco.fama@unige.it.
⁹ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy. Electronic address: lucia.argenti96@gmail.com.
¹⁰ Clinical Psychology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: gabriella.biffa@hsanmartino.it.
¹¹ Geriatrics Unit, Department of Geriatric Care, Orthogeriatrics and Rehabilitation, E.O. Galliera Hospital, Genoa, Italy. Electronic address: morgantiwanda@gmail.com.
¹² Geriatrics Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: silvia.buonopane09@gmail.com.
¹³ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: auccelli@neurologia.unige.it.
¹⁴ Department of Health Sciences, University of Genoa, Italy; Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: silviadaniela.morbelli@hsanmartino.it.
¹⁵ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Italy; Neurology Clinics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: matteo.pardini@unige.it.

PMID: 38113612
DOI: 10.1016/j.cortex.2023.11.011

Abstract

Background: SOMI (Stages of Objective Memory Impairment) is a novel classification that identifies six stages of memory decline in Alzheimer's Disease (AD) using the Free and Cued Selective Reminding Test (FCSRT). However, the relationship between SOMI stages and brain metabolism remains unexplored. This study aims to investigate the metabolic correlates of SOMI stages using FDG-PET in Mild Cognitive Impairment due to AD (MCI-AD) and early AD patients.

Methods: One hundred twenty-nine-patients (99 aMCI-AD and 30 AD), and 42 healthy controls (HCs) (MMSE = 29.2 ± .8; age:69.1 ± 8.6 years; education:10.7 ± 3.8 years) who underwent an extensive neuropsychological battery including FCSRT and brain FDG-PET were enrolled. According to their clinical relevance and available sample sizes, SOMI-4 (N = 24 subjects; MMSE score:26.6 ± 2.6: age:75.4 ± 3.2; education:9.9 ± 4.5) and SOMI-5 groups (N = 97; MMSE:25.3 ± 2.6; age:73.9 ± 5.8; education:9.4 ± 4.1) were investigated.

Results: Compared to HCs, SOMI-4 showed hypometabolism in the precuneus, medial temporal gyrus bilaterally, right pecuneus and angular gyrus. SOMI-5 exhibited broader hypometabolism, extending to the left posterior cingulate and medial frontal gyrus bilaterally. The conjunction analysis revealed overlapping areas in the precuneus, medial temporal gyrus bilaterally, and in the right angular gyrus and cuneus. The disjunction analysis identified SOMI-5 specific hypometabolism encompassing left inferior temporal gyrus, uncus and parahippocampal gyrus, and medial frontal gyrus bilaterally (p < .001, p-value (FWE) < .05).

Discussion: SOMI-4 relates to posterior hypometabolism, while SOMI-5 to more extensive hypometabolism further encompassing frontal cortices, suggesting SOMI as a biologically relevant classification system of memory decline.

Conclusion: Memory decline staged with SOMI is associated with hypometabolism spreading in amnesic MCI-AD/AD, suggesting its usefulness as a clinical marker of increasing neurodegeneration.

Keywords: FDG-PET; Free and cued selective reminding test; MCI-AD; Memory decline; Metabolic pattern.

MeSH terms

Aged
Alzheimer Disease* / metabolism
Brain / diagnostic imaging
Brain / metabolism
Cognitive Dysfunction* / complications
Disease Progression
Fluorodeoxyglucose F18 / metabolism
Humans
Memory Disorders / complications
Middle Aged
Positron-Emission Tomography

Substances

Fluorodeoxyglucose F18