Higher Coffee Consumption Is Associated With Slower Cognitive Decline and Less Cerebral Aβ-Amyloid Accumulation Over 126 Months: Data From the Australian Imaging, Biomarkers, and Lifestyle Study

WHOM do I ask the question? Is 12 cups a day high enough? I want to make sure I'm covered.

Higher Coffee Consumption Is Associated With Slower Cognitive Decline and Less Cerebral Aβ-Amyloid Accumulation Over 126 Months: Data From the Australian Imaging, Biomarkers, and Lifestyle Study

Samantha L. Gardener^1,2*, Stephanie R. Rainey-Smith^1,2,3,4, Victor L. Villemagne⁵, Jurgen Fripp⁶, Vincent Doré^6,7, Pierrick Bourgeat⁶, Kevin Taddei^1,2, Christopher Fowler⁸, Colin L. Masters⁸, Paul Maruff^8,9, Christopher C. Rowe^7,8, David Ames^10,11, Ralph N. Martins^1,2,12 and the AIBL Investigators^†

• ¹Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
• ²Australian Alzheimer’s Research Foundation, Sarich Neuroscience Research Institute, Perth, WA, Australia
• ³Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, WA, Australia
• ⁴School of Psychological Science, University of Western Australia, Perth, WA, Australia
• ⁵Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
• ⁶CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston, QLD, Australia
• ⁷Department of Molecular Imaging and Therapy, Centre for PET, Austin Health, Heidelberg, VIC, Australia
• ⁸The Florey Institute, The University of Melbourne, Parkville, VIC, Australia
• ⁹Cogstate Ltd., Melbourne, VIC, Australia
• ¹⁰National Ageing Research Institute, Parkville, VIC, Australia
• ¹¹Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, VIC, Australia
• ¹²Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia

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.

Introduction

Worldwide, a high proportion of adults drink coffee daily, making it one of the most popular beverages globally. Coffee contains a range of bioactive compounds, including caffeine, chlorogenic acid, polyphenols and small amounts of vitamins and minerals (Spiller, 1984). Epidemiological studies suggest coffee has beneficial effects on various conditions including stroke (Larsson and Orsini, 2011), heart failure (Mostofsky et al., 2012), cancers (Wang et al., 2016), diabetes (Akash et al., 2014), and Parkinson’s disease (Ross et al., 2000). Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive impairment of learning, memory and other cognitive deficits, with extracellular deposition of Aβ-amyloid (Aβ) protein within the brain leading to neuroinflammation, synaptic loss and neuronal death (Villemagne et al., 2013). Several studies suggest a protective role of coffee, with reduced risk of mild cognitive impairment (MCI) and AD reported (van Gelder et al., 2007; Eskelinen et al., 2009; Arab et al., 2011; Liu et al., 2016; Wierzejska, 2017; Wu et al., 2017). However, there are limited longitudinal data from cohorts of cognitively normal older adults describing associations of coffee consumption with distinct domains of cognition, and concurrently investigating potential neuropathological mechanisms underpinning any such associations.

Results from a meta-analysis conducted in 2016, which included nine published prospective cohort studies, found drinking one to two cups of coffee daily was associated with lower incidence of cognitive disorders (i.e., cognitive decline, cognitive impairment, AD, and all cause dementia) compared with less than one cup; studies ranged in follow-up from 1.3 to 28 years (Liu et al., 2016). Moreover, a recent cross-sectional analysis found self-reported lifetime intake of two or more cups of coffee per day was associated with lower rates of “Aβ positivity” (presence of significant brain Aβ), compared to less than two cups per day, in 411 non-demented older adults. However, current coffee intake was not related to “Aβ positivity” in this cohort, and neither current, nor lifetime intake, was related to cerebral mean cortical thickness or white matter hyperintensity volume (Kim et al., 2019). A second study investigating the effect of self-reported coffee consumption on brain volume found both high coffee consumption (≥ 4 cups per day) and low coffee consumption (no coffee or < 1 cup per day) to be associated with larger hippocampal volume cross-sectionally (p for test for quadratic trend = 0.001). There were no associations with volumes of the neocortex and striatum (accumbens, putamen, globus pallidus) or total intracranial volume. The cohort was homogeneous in nature, with all participants young Caucasian females (aged 23.2 ± 2.7 years), right handed with university education, and no history of smoking or drug/alcohol abuse (Perlaki et al., 2011). Conversely, higher self-reported coffee consumption (>3 cups/day compared to 0–1 cup/day) has also been associated cross-sectionally with smaller hippocampal volume, in 2914 individuals aged 59.28 ± 7.2 years (p = 0.033) (Araujo et al., 2016). However, this association was only observed when body mass index, previous coronary heart disease, alcohol consumption, and smoking were included in the statistical model, along with age, sex, and educational attainment (Araujo et al., 2016). Well-designed longitudinal cohort studies are necessary to further understand the influence of coffee consumption on AD phenotype and rates of decline in different cognitive domains.

The aim of the current study was to investigate the relationship of self-reported habitual coffee intake to rates of decline in varying cognitive domains, assessed using a comprehensive neuropsychological battery, over 126 months in 227 older adults classified as cognitively normal at baseline. Furthermore, we aimed to investigate whether habitual coffee intake was associated with rates of cerebral Aβ-amyloid deposition, or brain volume atrophy over the same time-period, in subsets of 60 and 51 participants, respectively. These investigations were conducted using data from the well-characterized Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL) (Fowler et al., 2021).