Anatomy and Neuroscience - Research Publications

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    Higher Coffee Consumption Is Associated With Slower Cognitive Decline and Less Cerebral A beta-Amyloid Accumulation Over 126 Months: Data From the Australian Imaging, Biomarkers, and Lifestyle Study
    Gardener, SL ; Rainey-Smith, SR ; Villemagne, VL ; Fripp, J ; Dore, V ; Bourgeat, P ; Taddei, K ; Fowler, C ; Masters, CL ; Maruff, P ; Rowe, CC ; Ames, D ; Martins, RN ; AIBL, I (FRONTIERS MEDIA SA, 2021-11-19)
    Background: Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer's disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations. Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over 126 months. In a subset of individuals, we also investigated the relationship between habitual coffee intake and cerebral Aβ-amyloid accumulation (n = 60) and brain volumes (n = 51) over 126 months. Results: Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown reliably to measure the first signs of cognitive decline in at-risk cognitively normal populations), and lower likelihood of transitioning to mild cognitive impairment or AD status, over 126 months. Higher baseline coffee consumption was also associated with slower Aβ-amyloid accumulation over 126 months, and lower risk of progressing to "moderate," "high," or "very high" Aβ-amyloid burden status over the same time-period. There were no associations between coffee intake and atrophy in total gray matter, white matter, or hippocampal volume. Discussion: Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption potentially reducing cognitive decline by slowing cerebral Aβ-amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ-amyloid-mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate whether coffee intake could be incorporated as a modifiable lifestyle factor aimed at delaying AD onset.
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    Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer's Disease
    Fowler, C ; Rainey-Smith, SR ; Bird, S ; Bomke, J ; Bourgeat, P ; Brown, BM ; Burnham, SC ; Bush, A ; Chadunow, C ; Collins, S ; Doecke, J ; Dore, V ; Ellis, KA ; Evered, L ; Fazlollahi, A ; Fripp, J ; Gardener, SL ; Gibson, S ; Grenfell, R ; Harrison, E ; Head, R ; Jin, L ; Kamer, A ; Lamb, F ; Lautenschlager, NT ; Laws, SM ; Li, Q-X ; Lim, L ; Lim, YY ; Louey, A ; Macaulay, SL ; Mackintosh, L ; Martins, RN ; Maruff, P ; Masters, CL ; McBride, S ; Milicic, L ; Peretti, M ; Pertile, K ; Porter, T ; Radler, M ; Rembach, A ; Robertson, J ; Rodrigues, M ; Rowe, CC ; Rumble, R ; Salvado, O ; Savage, G ; Silbert, B ; Soh, M ; Sohrabi, HR ; Taddei, K ; Taddei, T ; Thai, C ; Trounson, B ; Tyrrell, R ; Vacher, M ; Varghese, S ; Villemagne, VL ; Weinborn, M ; Woodward, M ; Xia, Y ; Ames, D (IOS PRESS, 2021-01-01)
    BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). OBJECTIVE: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. METHODS: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. RESULTS: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. CONCLUSION: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.
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    Longitudinal Trajectories in Cortical Thickness and Volume Atrophy: Superior Cognitive Performance Does Not Protect Against Brain Atrophy in Older Adults
    Gardener, SL ; Weinborn, M ; Sohrabi, HR ; Doecke, JD ; Bourgeat, P ; Rainey-Smith, SR ; Shen, K-K ; Fripp, J ; Taddei, K ; Maruff, P ; Salvado, O ; Savage, G ; Ames, D ; Masters, CL ; Rowe, CC ; Martins, RN ; O’Bryant, S (IOS PRESS, 2021-01-01)
    BACKGROUND: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. OBJECTIVE: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. METHODS: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30-44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. RESULTS: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. CONCLUSION: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.
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    SPON1 Is Associated with Amyloid-beta and APOE epsilon 4-Related Cognitive Decline in Cognitively Normal Adults
    Fernandez, S ; Burnham, SC ; Milicic, L ; Savage, G ; Maruff, P ; Peretti, M ; Sohrabi, HR ; Lim, YY ; Weinborn, M ; Ames, D ; Masters, CL ; Martins, RN ; Rainey-Smith, S ; Rowe, CC ; Salvado, O ; Groth, D ; Verdile, G ; Villemagne, VL ; Porter, T ; Laws, SM (IOS PRESS, 2021-01-01)
    BACKGROUND: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. OBJECTIVE: The aim of this study was to assess whether the association was present in cognitively normal older adults. METHODS: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. RESULTS: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ɛ4 and rs11023139 in individuals with high amyloid-β burden. APOE ɛ4/rs11023139-A carriers declined significantly faster than APOE ɛ4/rs11023139-G_G carriers in measures of global cognition (p = 0.011) and verbal episodic memory (p = 0.020). CONCLUSION: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ɛ4 cognitively normal older adults with a high neocortical amyloid-β burden.
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    Learning deficit in cognitively normal APOE epsilon 4 carriers with LOW beta-amyloid
    Lim, YY ; Baker, JE ; Mills, A ; Bruns, L ; Fowler, C ; Fripp, J ; Rainey-Smith, SR ; Ames, D ; Masters, CL ; Maruff, P (WILEY, 2021-01-01)
    INTRODUCTION: In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ-) apolipoprotein E (APOE) ε4 carriers. We aimed to determine the effect of ε4 on the ability to benefit from experience (ie, learn) in Aβ- CNs. METHODS: Aβ- CNs (n = 333) underwent episodic memory assessments every 18 months for 108 months. A subset (n = 48) completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT) over 6 days. RESULTS: Aβ- ε4 carriers showed significantly lower rates of improvement on episodic memory over 108 months compared to non-carriers (d = 0.3). Rates of learning on the ORCA-LLT were significantly slower in Aβ- ε4 carriers compared to non-carriers (d = 1.2). DISCUSSION: In Aβ- CNs, ε4 is associated with a reduced ability to benefit from experience. This manifested as reduced practice effects (small to moderate in magnitude) over 108 months on the episodic memory composite, and a learning deficit (large in magnitude) over 6 days on the ORCA-LLT. Alzheimer's disease (AD)-related cognitive abnormalities can manifest before preclinical AD thresholds.
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    Association of beta-Amyloid Level, Clinical Progression, and Longitudinal Cognitive Change in Normal Older Individuals
    Van der Kall, LM ; Thanh, T ; Burnham, SC ; Dore, V ; Mulligan, RS ; Bozinovski, S ; Lamb, F ; Bourgeat, P ; Fripp, J ; Schultz, S ; Lim, YY ; Laws, SM ; Ames, D ; Fowler, C ; Rainey-Smith, SR ; Martins, RN ; Salvado, O ; Robertson, J ; Maruff, P ; Masters, CL ; Villemagne, VL ; Rowe, CC (LIPPINCOTT WILLIAMS & WILKINS, 2021-02-02)
    OBJECTIVE: To determine the effect of β-amyloid (Aβ) level on progression risk to mild cognitive impairment (MCI) or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals. METHODS: All CN from the Australian Imaging Biomarkers and Lifestyle study with Aβ PET and ≥3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aβ positive; follow-up 5.3 ± 1.7 years). Aβ level was divided using the standardized 0-100 Centiloid scale: <15 CL negative, 15-25 CL uncertain, 26-50 CL moderate, 51-100 CL high, >100 CL very high, noting >25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline. RESULTS: Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high, and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% confidence interval [CI] 1.3-7.6; p < 0.05), for high was 7.0 (95% CI 3.7-13.3; p < 0.001), and for very high was 11.4 (95% CI 5.1-25.8; p < 0.001). Decline in cognitive composite score was minimal in the moderate group (-0.02 SD/year, p = 0.05), while the high and very high declined substantially (high -0.08 SD/year, p < 0.001; very high -0.35 SD/year, p < 0.001). CONCLUSION: The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26-50 CL to 28% if 51-100 CL and 50% if >100 CL. This information may be useful for dementia risk counseling and aid design of preclinical AD trials.
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    Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer's disease
    Roe, JM ; Vidal-Pineiro, D ; Sorensen, O ; Brandmaier, AM ; Duzel, S ; Gonzalez, HA ; Kievit, RA ; Knights, E ; Kuhn, S ; Lindenberger, U ; Mowinckel, AM ; Nyberg, L ; Park, DC ; Pudas, S ; Rundle, MM ; Walhovd, KB ; Fjell, AM ; Westerhausen, R (NATURE RESEARCH, 2021-02-01)
    Aging and Alzheimer's disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Asymmetry-change was further accelerated in AD. Results suggest a system-wide dedifferentiation of the adaptive asymmetric organization of heteromodal cortex in aging and AD.