Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;94(1):259-279.
doi: 10.3233/JAD-221274.

Medial Temporal Lobe Atrophy in Predementia Alzheimer's Disease: A Longitudinal Multi-Site Study Comparing Staging and A/T/N in a Clinical Research Cohort

Jonas Alexander Jarholm  1   2 , Atle Bjørnerud  3   4   5 , Turi Olene Dalaker  6 , Mehdi Sadat Akhavi  7 , Bjørn Eivind Kirsebom  8   9 , Lene Pålhaugen  1   2 , Kaja Nordengen  1   2 , Gøril Rolfseng Grøntvedt  10   11 , Arne Nakling  12 , Lisa F Kalheim  1   2 , Ina S Almdahl  1   2 , Sandra Tecelão  1 , Tormod Fladby  1   2 , Per Selnes  1   2
Affiliations

Medial Temporal Lobe Atrophy in Predementia Alzheimer's Disease: A Longitudinal Multi-Site Study Comparing Staging and A/T/N in a Clinical Research Cohort

Jonas Alexander Jarholm et al. J Alzheimers Dis. 2023.

Erratum in

Abstract

Background: Atrophy of the medial temporal lobe (MTL) is a biological characteristic of Alzheimer's disease (AD) and can be measured by segmentation of magnetic resonance images (MRI).

Objective: To assess the clinical utility of automated volumetry in a cognitively well-defined and biomarker-classified multi-center longitudinal predementia cohort.

Methods: We used Automatic Segmentation of Hippocampal Subfields (ASHS) to determine MTL morphometry from MRI. We harmonized scanner effects using the recently developed longitudinal ComBat. Subjects were classified according to the A/T/N system, and as normal controls (NC), subjective cognitive decline (SCD), or mild cognitive impairment (MCI). Positive or negative values of A, T, and N were determined by cerebrospinal fluid measurements of the Aβ42/40 ratio, phosphorylated and total tau. From 406 included subjects, longitudinal data was available for 206 subjects by stage, and 212 subjects by A/T/N.

Results: Compared to A-/T-/N- at baseline, the entorhinal cortex, anterior and posterior hippocampus were smaller in A+/T+orN+. Compared to NC A- at baseline, these subregions were also smaller in MCI A+. Longitudinally, SCD A+ and MCI A+, and A+/T-/N- and A+/T+orN+, had significantly greater atrophy compared to controls in both anterior and posterior hippocampus. In the entorhinal and parahippocampal cortices, longitudinal atrophy was observed only in MCI A+ compared to NC A-, and in A+/T-/N- and A+/T+orN+ compared to A-/T-/N-.

Conclusion: We found MTL neurodegeneration largely consistent with existing models, suggesting that harmonized MRI volumetry may be used under conditions that are common in clinical multi-center cohorts.

Keywords: Alzheimer’s disease; brain atrophy; cognitive decline; hippocampus; longitudinal studies; magnetic resonance imaging.

PubMed Disclaimer

Conflict of interest statement

T. Fladby has served on a Novo Nordisk and Biogen advisory boards.

All other authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Flow-chart of participant selection from the DDI-cohort. A cohort of 406 subjects had baseline MRI data with ASHS (Automated segmentation of Hippocampal Subfields). Subjects included in the left arm had available A/T/N-classification at baseline, and subjects included in the right arm had available cognitive staging and amyloid status.
Fig. 2
Fig. 2
Graphics: MTL subregional longitudinal volume loss. Longitudinal plots of ERC and Posterior hippocampus volume loss according to A) Clinical staging and amyloid status and B) A/T/N classification.
Fig. 3
Fig. 3
Graphics: ROC curves. Additional ROC analysis were performed to examine the performance in classifying MCI A+ from NC A– controls at baseline. ERC and Posterior hippocampus had similar performance (ERC had Area under the curve (AUC) of 0,717 and Posterior Hippocampus had AUC of 0.672). ROC analyses were also performed to examine the performance in classifying A+/T+orN+ from biomarker negative controls (A–/T–/N–) at baseline, where both ERC and Posterior hippocampus also had similar performance (ERC had AUC of 0.659 and posterior hippocampus had AUC of 0.722).
Fig. 4
Fig. 4
Overview of subregional segmentation by ASHS-T1 (including the hippocampal formation and MTL cortex).
Fig. 5
Fig. 5
Detailed overview of study design.
See this image and copyright information in PMC

References

    1. Lam B, Masellis M, Freedman M, Stuss DT, Black SE (2013) Clinical, imaging, and pathological heterogeneity of the Alzheimer’s disease syndrome. Alzheimers Res Ther 5, 1. - PMC - PubMed
    1. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 82, 239–259. - PubMed
    1. Iqbal K, Liu F, Gong C-X, Alonso A del C, Grundke-Iqbal I (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol (Berl) 118, 53–69. - PMC - PubMed
    1. Fukutani Y, Cairns NJ, Shiozawa M, Sasaki K, Sudo S, Isaki K, Lantos PL (2000) Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer’s disease. Psychiatry Clin Neurosci 54, 523–529. - PubMed
    1. Bobinski M, Wegiel J, Tarnawski M, Bobinski M, Reisberg B, de Leon MJ, Miller DC, Wisniewski HM (1997) Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease. J Neuropathol Exp Neurol 56, 414–420. - PubMed

Publication types

MeSH terms