Zea‐Sevilla, María Ascensión;
Uceda‐Heras, Alicia;
Rabano, Alberto
The imprint of sex on the heterogeneity of Alzheimer's disease sex differences in advanced Alzheimer’s disease: A clinical‐pathological study
: Human neuropathology/clinico‐pathologic correlations
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Medientyp:
E-Artikel
Titel:
The imprint of sex on the heterogeneity of Alzheimer's disease sex differences in advanced Alzheimer’s disease: A clinical‐pathological study
:
Human neuropathology/clinico‐pathologic correlations
Beteiligte:
Zea‐Sevilla, María Ascensión;
Uceda‐Heras, Alicia;
Rabano, Alberto
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Alzheimer's disease(AD) displays both clinical and pathological heterogeneity, and the effects of sex difference on various neuropathological, functional and epidemiological aspects of AD are currently under study. The existence of sex‐specific clinical‐pathological phenotypes is still unknown, but the accumulated evidence indicates specific patterns as well as clinical‐pathological differences suggesting that sex is a crucial variable in the heterogeneity of the disease. Hippocampal sclerosis (HS) is characterized by selective neuronal loss and gliosis of the CA 1 region of the hippocampus and the subiculum associated with age and multiple pathologies such as AD, and has recently been included in Limbic‐predominant aging‐related TDP‐43 encepahalopathy (LATE). The aim of this study is to know if AD patients with HS show sex‐specific difference both at a neuropathological and a clinical level.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>A full postmortem neuropathological study was performed on 126 consecutive brains from a clinicopathologic cohort of institutionalized dementia patients (Vallecas Alzheimer’s Center Study), mean age at death(87.3 ± 6.6), sex ratio(79.4% females), with a predominant primary diagnosis of Alzheimer’s disease(77.6%).HS was defined based on morphologic criteria including pre‐HS changes defined by our group.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>69.79 % of AD patients displayed HS(women 83.58%, male 16.41%).Clinical disease onset was earlier in men 72.93 ± 9.3 vs 77.19 ± 6.57 (p < 0.05). In women, the presence of HS is associated with a later disease onset 78.67 ± 6.03 vs 75.05 ± 6.40 (p = 0.05), a later age at exitus 90.44 ± 5.33 vs 84.95 ± 6.62 (p < 0.05) and a longer survival time 11.78±3.85 vs 9.45 ± 4.69 (p < 0.05). In men, these variables also differed between HS+ and HS‐ subjects, but did not reach statistical significance. APOE4 was not associated with HS in any sex group.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In our study, the difference in the age of disease onset, age of exitus and survival time in the presence of HS is linked to sex. Sex is an important factor in the phenotypic heterogeneity of AD, and male sex predominates in earlier onset AD with hippocampal preservation while later onset and limbic‐predominant disease is higher in women. In this axis of phenotypic variability, HS is a determinant factor. These disease phenotypes may be relevant to a "precision medicine" approach and should be considered in the development of therapeutic strategies and clinical trials for AD.</jats:p></jats:sec>