Sex differences in functional and molecular neuroimaging biomarkers of Alzheimer's disease in cognitively normal older adults with subjective memory complaints

Cavedo, Enrica; Houot, Marion; Ferretti, Maria Teresa; Grothe, Michel J.; Teipel, Stefan J.; Lista, Simone; Habert, Marie‐Odile; Potier, Marie‐Claude; Dubois, Bruno; Hampel, Harald; Bakardjian, Hovagim; Benali, Habib; Bertin, Hugo; Bonheur, Joel; Boukadida, Laurie; Boukerrou, Nadia; Chiesa, Patrizia Andrea; Colliot, Olivier; Dubois, M.; Epelbaum, Stéphane; Gagliardi, Geoffroy; Genthon, Rémy; Kas, Aurélie; Lamari, Foudil; Lévy, Marcel; Metzinger, Christiane; Mochel, Fanny; Nyasse, Francis; Poisson, Catherine; Revillon, Marie; Santos, Antonio; Andrade, Katia Santos; Solé, Marine; Surtee, Mohmed; Schotten, Michel Thiebaud de; Vergallo, Andrea; Younsi, Nadjia; Aguilar, Lisi Flores; Babiloni, Claudio; Baldacci, Filippo; Benda, Norbert; Black, Keith L.; Bokde, Arun L.W.; Bonuccelli, Ubaldo; Broich, Karl; Bun, René Sosata; Cacciola, Francesco; Castrillo, Juan I.; Ceravolo, Roberto; Coman, Cristina-Maria; Corvol, Jean‐Christophe; Cuello, A. Claudio; Cummings, Jeffrey L.; Depypere, Herman; Duggento, Andrea; Durrleman, Stanley; Escott‐Price, Valentina; Federoff, Howard J.; Fiandaca, Massimo S.; Frank, Richard A.; Garaci, Francesco; George, Nathalie; Giorgi, Filippo Sean; Graziani, Manuela; Haberkamp, Marion; Herholz, Karl; Karran, Eric; Kim, Seung H.; Koronyo, Yosef; Koronyo‐Hamaoui, Maya; Langevin, Todd; Lehericy, Stéphane; Lorenceau, Jean; Mapstone, Mark; Néri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; O’Bryant, Sid; Perry, George; Ritchie, Craig W.; Rojkova, Katrine; Rossi, Símone; Saidi, Amira; Santarnecchi, Emiliano; Schneider, Lon S.; Sporns, Olaf; Toschi, Nicola; Verdooner, Steven R.; Villain, Nicolas; Welikovitch, Lindsay A.; Woodcock, Janet; Younesi, Erfan

doi:10.1016/j.jalz.2018.05.014

Cited by 81 publications

(61 citation statements)

References 85 publications

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“…One study suggested that women have early neural resistance to Aβ [40]. However, other studies found that men had greater Aβ burden than women [41,42]. One longitudinal PET study found no differences in rate of Aβ accumulation by sex [5], although another found that rates were greater in men than women, although this effect went away after correcting for baseline Aβ burden [4].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Amyloid-β PET in Atypical Alzheimer’s Disease and Frontotemporal Lobar Degeneration

Whitwell

Tosakulwong

Weigand

et al. 2020

JAD

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Background: Rates of beta-amyloid (Aβ) accumulation have been characterized across the cognitively normal to typical Alzheimer's dementia spectrum, but little is known about Aβ accumulation in atypical Alzheimer's disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD). We aimed to characterize longitudinal Aβ accumulation, and determine the influence of age, apolipoprotein E genotype, disease duration, and sex in atypical AD and FTLD. Methods: 322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serial PiB-PET scans (42 atypical AD, 31 FTLD). Global Aβ standard uptake value ratios were calculated for every scan. Mixed effects models were used to assess the effect of age, APOE genotype, disease duration, and sex on baseline and change measures of Aβ. Results: Atypical AD showed higher baseline Aβ than FTLD. Rate of Aβ accumulation was not associated with baseline Aβ in either group. Older age was associated with greater baseline Aβ and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOE e4 genotype was associated with greater baseline Aβ in FTLD but did not influence rates of accumulation. Rates of Aβ accumulation were faster in FTLD patents with time from onset-to-PET ≤4 years. Female sex was associated with faster rates of accumulation in atypical AD.

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Section: Discussionmentioning

confidence: 99%

Longitudinal Amyloid-β PET in Atypical Alzheimer’s Disease and Frontotemporal Lobar Degeneration

Whitwell

Tosakulwong

Weigand

et al. 2020

JAD

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“… Swinford et al (2018) [ 50 ] E-Cog 18 F-flortaucipir PET Cross-sectional CN: n=40(76.48±7.211) SMC: n=11(71.55±5.11) EMCI: n=31(75.32±7.29) Memory concern and the self-perception relate to tau aggregation. Cavedo et al (2018) [ 60 ] Memory complaints 18 F-flortaucipir -PET FDG-PET MRI Cross-sectional Women: n=201(76.02±3.24) Men: n=117(76.05±3.85) Men had higher amyloid load glucose hypometabolism and lower RSFC. Gardener et al (2016) [ 58 ] 1 binary question FDG-PET Cross-sectional All: n=43(66±10.1) Non-SMC: n=23(66±8.9) SMC: n=20 (68±11.4) Positive association between memory immediate recall and FDG-PET SUVR in the right amygdala in SMC individuals.…”

Section: Positron Emission Tomographymentioning

confidence: 99%

“…Furthermore, some studies also explored the interactions of SCD with other risk factors for dementia due to AD and their effects on FC. Cavedo et al [ 60 ] found sex-specific alterations in the resting state (FC) of the DMN. The study conducted by Chiesa et al revealed that ApoE ɛ4 carriers presented a slower longitudinal increase in FC in the frontal lobes than noncarriers [ 140 ].…”

Section: Functional Mrimentioning

confidence: 99%

Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease

Wang

Huang

et al. 2020

Mol Neurodegeneration

125

135

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Subjective cognitive decline (SCD) is regarded as the first clinical manifestation in the Alzheimer’s disease (AD) continuum. Investigating populations with SCD is important for understanding the early pathological mechanisms of AD and identifying SCD-related biomarkers, which are critical for the early detection of AD. With the advent of advanced neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), accumulating evidence has revealed structural and functional brain alterations related to the symptoms of SCD. In this review, we summarize the main imaging features and key findings regarding SCD related to AD, from local and regional data to connectivity-based imaging measures, with the aim of delineating a multimodal imaging signature of SCD due to AD. Additionally, the interaction of SCD with other risk factors for dementia due to AD, such as age and the Apolipoprotein E (ApoE) ɛ4 status, has also been described. Finally, the possible explanations for the inconsistent and heterogeneous neuroimaging findings observed in individuals with SCD are discussed, along with future directions. Overall, the literature reveals a preferential vulnerability of AD signature regions in SCD in the context of AD, supporting the notion that individuals with SCD share a similar pattern of brain alterations with patients with mild cognitive impairment (MCI) and dementia due to AD. We conclude that these neuroimaging techniques, particularly multimodal neuroimaging techniques, have great potential for identifying the underlying pathological alterations associated with SCD. More longitudinal studies with larger sample sizes combined with more advanced imaging modeling approaches such as artificial intelligence are still warranted to establish their clinical utility.

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“…[17]). However, it should be noted that some regional differences have been observed in cognitively normal older adults with subjective memory complaints, where men showed higher PET‐amyloid load in the anterior cingulate cortex than women [121]. Such regional differences might deserve to be further investigated.…”

Section: Alzheimer’s Disease Diagnosis and Biomarkersmentioning

confidence: 99%

Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice

Ferretti

Martínková

Biskup

et al. 2020

Euro J of Neurology

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Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.

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Sex differences in functional and molecular neuroimaging biomarkers of Alzheimer's disease in cognitively normal older adults with subjective memory complaints

Abstract: Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.

Cited by 81 publications

References 85 publications

Longitudinal Amyloid-β PET in Atypical Alzheimer’s Disease and Frontotemporal Lobar Degeneration

Longitudinal Amyloid-β PET in Atypical Alzheimer’s Disease and Frontotemporal Lobar Degeneration

Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease

Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice

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