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Title: | Differential Effects of APOE and Modifiable Risk Factors on Hippocampal Volume Loss and Memory Decline in Aβ- and Aβ+ Older Adults. | Austin Authors: | Rosenich, Emily;Bransby, Lisa;Yassi, Nawaf;Fripp, Jurgen;Laws, Simon M;Martins, Ralph N;Fowler, Christopher;Rainey-Smith, Stephanie R;Rowe, Christopher C ;Masters, Colin L ;Maruff, Paul;Lim, Yen Ying | Affiliation: | Florey Institute of Neuroscience and Mental Health University of Melbourne; Molecular Imaging and Therapy Medicine (University of Melbourne) School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley Cogstate Ltd., Melbourne, Australia CSIRO Health and Biosecurity, Australian e-Health Research Centre, Brisbane Collaborative Genomics and Translation Group, School of Medical and Health Sciences Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup Centre for Healthy Ageing, Health Futures Institute, Murdoch University Australian Alzheimer's Research Foundation, Sarich Neuroscience Research Institute, Nedlands Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital. Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville Turner Institute for Brain and Mental Health, School of Psychological Sciences Monash University, Clayton |
Issue Date: | 26-Apr-2022 | Date: | 2022-02-15 | Publication information: | Neurology 2022; 98(17): e1704-e1715 | Abstract: | This prospective study sought to determine the association of modifiable/nonmodifiable components included in the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score with hippocampal volume (HV) loss and episodic memory (EM) decline in cognitively normal (CN) older adults classified as brain β-amyloid (Aβ) negative (Aβ-) or positive (Aβ+). Australian Imaging, Biomarkers and Lifestyle study participants (age 58-91 years) who completed ≥2 neuropsychological assessments and a brain Aβ PET scan (n = 592) were included in this study. We computed the CAIDE risk score (age, sex, APOE ε4 status, education, hypertension, body mass index [BMI], hypercholesterolemia, physical inactivity) and a modifiable CAIDE risk score (CAIDE-MR; education, hypertension, BMI, hypercholesterolemia, physical inactivity) for each participant. Aβ+ was classified using Centiloid >25. Linear mixed models assessed interactions between each CAIDE score, Aβ group, and time on HV loss and EM decline. Age, sex, and APOE ε4 were included as separate predictors in CAIDE-MR models to assess differential associations. Exploratory analyses examined relationships between individual modifiable risk factors and outcomes in Aβ- cognitively normal (CN) adults. We observed a significant Aβ group × CAIDE × time interaction on HV loss (β [SE] = -0.04 [0.01]; p < 0.000) but not EM decline (β [SE] = -2.33 [9.96]; p = 0.98). Decomposition revealed a significant CAIDE × time interaction in Aβ+ participants only. When modifiable/nonmodifiable CAIDE components were considered separately, we observed a significant Aβ group × CAIDE-MR × time interaction on EM decline only (β [SE] = 3.03 [1.18]; p = 0.01). A significant CAIDE-MR score × time interaction was observed in Aβ- participants only. Significant interactions between APOE ε4 and age × time on HV loss and EM decline were observed in both groups. Exploratory analyses in Aβ- CN participants revealed a significant interaction between BMI × time on EM decline (β [SE] = -3.30 [1.43]; p = 0.02). These results are consistent with studies showing that increasing age and APOE ε4 are associated with increased rates of HV loss and EM decline. In Aβ- CN adults, lower prevalence of modifiable cardiovascular risk factors was associated with less HV loss and EM decline over ∼10 years, suggesting interventions to reduce modifiable cardiovascular risk factors could be beneficial in this group. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/30068 | DOI: | 10.1212/WNL.0000000000200118 | ORCID: | 0000-0002-7600-9277 0000-0002-2846-6895 0000-0002-0685-0060 0000-0001-9705-0079 0000-0002-4355-7082 0000-0002-4828-9363 0000-0003-1397-0359 0000-0003-3910-2453 0000-0003-3072-7940 0000-0002-6947-9537 0000-0002-0308-5156 |
Journal: | Neurology | PubMed URL: | 35169009 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/35169009/ | Type: | Journal Article |
Appears in Collections: | Journal articles |
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