Clinical relevance of brain atrophy subtypes categorization in memory clinics

Planche, Vincent; Bouteloup, Vincent; Mangin, Jean‐François; Dubois, Bruno; Delrieu, Julien; Pasquier, Florence; Blanc‬, ‪Frederic; Paquet, Claire; Hanon, Olivier; Gabelle, Audrey; Ceccaldi, M.; Annweiler, Cédric; Krolak‐Salmon, Pierre; Habert, Marie‐Odile; Fischer, Clara; Chupin, Marie; Béjot, Yannick; Godefroy, Olivier; Wallon, David; Sauvée, Mathilde; Bourdel‐Marchasson, Isabelle; Jalenques, Isabelle; Tison, François; Chêne, Geneviève; Dufouil, Carole

doi:10.1002/alz.12231

Cited by 19 publications

(22 citation statements)

References 43 publications

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“…We did not find any differences in the progression rate between the hippocampal subtypes. Previous studies have found conflicting results concerning the progression rate in atrophy subtypes [3, 6-8, 11, 12]. As we do not know the cortical atrophy component in the patients in the present study and cortical atrophy has been found to be the driver of progression rate, conclusions are hard to make based on our data [11].…”

Section: Discussioncontrasting

confidence: 81%

“…Findings on the clinical progression rate of the various subtypes have been inconsistent. Some studies reported a faster progression in typical and hippocampal sparing AD [3, 6, 11], and others have found faster progression in typical and limbic predominant types [7, 12], while our group did not find any difference in the progression rate in a previous study [8]. The focus on AD subtypes is important as differences in clinical symptomatology, progression rate, regional vulnerability, and possibly underlying neurobiology could have a major impact on both clinical workup and follow-up and in treatment trials [13].…”

Section: Introductionmentioning

confidence: 99%

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Hippocampal Atrophy Subtypes of Alzheimer’s Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications

Persson

Edwin

Knapskog

et al. 2022

Dement Geriatr Cogn Disord

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Introduction: One pathological hallmark of Alzheimer’s disease (AD) is atrophy of medial temporal brain regions that can be visualized on magnetic resonance imaging (MRI), but not all patients will have atrophy. The aim was to use MRI to categorize patients according to their hippocampal atrophy status and to present prevalence of the subtypes, difference in clinical symptomatology and progression, and factors associated with hippocampal subtypes. Methods: We included 215 patients with AD who had been assessed with the clinically available MRI software NeuroQuant (NQ; CorTechs labs/University of California, San Diego, CA, USA). NQ measures the hippocampus volume and calculates a normative percentile. Atrophy was regarded to be present if the percentile was ≤5. Demographics, cognitive measurements, AD phenotypes, apolipoprotein E status, and results from cerebrospinal fluid and amyloid positron emission tomography analyses were included as explanatory variables of the hippocampal subtypes. Results: Of all, 60% had no hippocampal atrophy. These patients were younger and less cognitively impaired concerning global measures, memory function, and abstraction but impaired concerning executive, visuospatial, and semantic fluency, and more of them had nonamnestic AD, compared to those with hippocampal atrophy. No difference in progression rate was observed between the two groups. In mild cognitive impairment patients, amyloid pathology was associated with the no hippocampal atrophy group. Conclusion: The results have clinical implications. Clinicians should be aware of the large proportion of AD patients presenting without atrophy of the hippocampus as measured with this clinical MRI method in the diagnostic set up and that nonamnestic phenotypes are more common in this group as compared to those with atrophy. Furthermore, the findings are relevant in clinical trials.

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Section: Discussioncontrasting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Hippocampal Atrophy Subtypes of Alzheimer’s Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications

Persson

Edwin

Knapskog

et al. 2022

Dement Geriatr Cogn Disord

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“…From the conceptual point of view, it is essential to keep in mind that the present MRI staging scheme (such as the Braak staging scheme) only describes the most frequent ‘limbic-predominant’ and ‘typical’ progressions of Alzheimer’s disease. 36 , 37 This model only describes the ‘average’ structural course of Alzheimer’s disease and does not apply to ‘atypical’ Alzheimer’s disease, such as logopenic primary progressive aphasia, posterior cortical atrophy or behavioural Alzheimer’s disease, which are driven by different patterns of atrophy and represent less common ‘extremes’ of the Alzheimer’s disease anatomical spectrum. 38 Indeed, the methodology used in the present work does not take into account the recent description by Vogel et al 39 of distinct trajectories of tau deposition in Alzheimer’s disease.…”

Section: Discussionmentioning

confidence: 99%

Structural progression of Alzheimer’s disease over decades: the MRI staging scheme

Planche

Manjón

Mansencal

et al. 2022

Brain Communications

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The chronological progression of brain atrophy over decades, from presymptomatic to dementia stages, has never been formally depicted in Alzheimer’s disease. This is mainly due to the lack of cohorts with long enough MRI follow-ups in cognitively unimpaired young participants at baseline. To describe a spatiotemporal atrophy staging of Alzheimer’s disease at the whole-brain level, we built extrapolated lifetime volumetric models of healthy and Alzheimer’s disease brain structures by combining multiple large-scale databases (n = 3512 quality controlled MRI from 9 cohorts of subjects covering the entire lifespan, including 415 MRI from ADNI1, ADNI2, and AIBL for Alzheimer’s disease patients). Then, we validated dynamic models based on cross-sectional data using external longitudinal data. Finally, we assessed the sequential divergence between normal aging and Alzheimer’s disease volumetric trajectories and described the following staging of brain atrophy progression in Alzheimer’s disease: (1) hippocampus and amygdala; (2) middle temporal gyrus; (3) entorhinal cortex, parahippocampal cortex, and other temporal areas; (4) striatum and thalamus and (5) middle frontal, cingular, parietal, insular cortices and pallidum. We concluded that this MRI scheme of atrophy progression in Alzheimer’s disease was close but did not entirely overlap with Braak staging of tauopathy, with a “reverse chronology” between limbic and entorhinal stages. Alzheimer’s disease structural progression may be associated with local tau accumulation but may also be related to axonal degeneration in remote sites and other limbic-predominant associated proteinopathies.

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“…More and more studies demonstrated the limbic-predominant atrophy pattern of AD [ 43 – 45 ]: the thickness of the isthmus cingulate was reported to decrease in AD patients and it was also shown to be associated with the cognitive level [ 46 , 47 ]. Our results further support the role of the isthmus cingulate in the progression of AD.…”

Section: Discussionmentioning

confidence: 99%

Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study

Zhang

et al. 2021

Transl Psychiatry

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Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.

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Clinical relevance of brain atrophy subtypes categorization in memory clinics

Cited by 19 publications

References 43 publications

Hippocampal Atrophy Subtypes of Alzheimer’s Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications

Hippocampal Atrophy Subtypes of Alzheimer’s Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications

Structural progression of Alzheimer’s disease over decades: the MRI staging scheme

Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study

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