Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Inspection time in non-demented older adults with mild cognitive impairment

The aim of this study was to examine inspection time (IT) performance in older adults with mild cognitive impairment (MCI), who are at higher risk of developing further cognitive decline or dementia. IT is described as an index of speed of informational intake. IT correlates with measures of fluid intelligence and is possibly a marker for the integrity of the cholinergic system of the brain. IT may therefore be useful in aiding the diagnosis of early-stage progressive cognitive impairment. The current study compares IT in 28 people with MCI to 28 age, gender and education-matched controls. The computer-based, visual IT task required participants to discriminate between two visual stimuli that were presented for brief periods. Participants' IT performance was compared to their performance on cognitive and memory tasks. Group comparison showed that participants with MCI performed significantly worse on IT than controls and was not affected by years of education. In combination with other clinical, neuropsychological and biological tests, IT may be a useful assessment tool for improving the identification of older adults at risk for clinically relevant cognitive decline

P3-182: Frequency of forgetting is associated with olfactory functions in healthy, community-dwelling elderly

Background: Olfactory dysfunction and subjective memory complaints (SMC) have been separately reported in Alzheimer’s disease (AD) patients and in people at risk of developing AD or at a prodromal phase of the disease, such as mild cognitive impairment (MCI). However, SMC and olfactory dysfunction have also been reported in the healthy elderly and in other neurodegenerative diseases such as Parkinson’s disease. The current study was designed to examine the association of frequency of forgetting and the olfactory threshold, discrimination, and identification in the healthy, community elderly. Methods: The sample compromised 107 participants (29 male and 78 female) derived from an ongoing longitudinal cohort of 530 healthy, elderly participants in Western Australia. The Sniffin’ Sticks was used to measure the different olfactory functions. The Sniffin’ Sticks provides four different scores including the olfactory threshold, discrimination, identification, and a total score (namely, TDI). Subjective memory complaints were tested using two measures: i) a single “yes/no” question derived from CAMDX-R, and ii) the frequency of forgetting subscale of Memory Functioning Questionnaire. Results: There was no significant difference between male/female and SMC/ control groups with respect to age, performance on Mini Mental Status Ex- amination (MMSE), and premorbid IQ. The SMC group was significantly different from the control group on olfactory threshold (P⬍0.05) and identification (P⬍0.05). There was a significant correlation between age and olfactory threshold. The frequency of forgetting showed significant correlations with olfactory discrimination and identification (both significant at: P⬍0.01). Age was the best predictor of threshold, while frequency of forgetting was a better predictor for olfactory discrimination and identification in comparison to age, sex, and depression. Conclusions: There were significant associations between SMC and those olfactory functions related to memory for olfactory stimuli. Though further investigation is needed for a definitive conclusion, these findings have important implications for the development of future screening instruments and better diagnostic criteria for AD

Associations of neighborhood environment with brain imaging outcomes in the Australian Imaging, Biomarkers and Lifestyle cohort

Introduction “Walkable” neighborhoods offer older adults opportunities for activities that may benefit cognition-related biological mechanisms. These have not previously been examined in this context. Methods We objectively assessed neighborhood walkability for participants (n = 146) from the Australian Imaging, Biomarkers and Lifestyle study with apolipoprotein E (APOE) genotype and two 18-month-apart brain volumetric and/or amyloid β burden assessments. Linear mixed models estimated associations of neighborhood walkability with levels and changes in brain imaging outcomes, the moderating effect of APOE ε4 status, and the extent to which associations were explained by physical activity. Results Cross-sectionally, neighborhood walkability was predictive of better neuroimaging outcomes except for left hippocampal volume. These associations were to a small extent explained by physical activity. APOE ε4 carriers showed slower worsening of outcomes if living in walkable neighborhoods. Discussion These findings indicate associations between neighborhood walkability and brain imaging measures (especially in APOE ε4 carriers) minimally attributable to physical activity