Is coffee protective against AD?

Habitual consumption of coffee may be protective against Alzheimer’s disease (AD), suggests a longitudinal study from Australia.

Despite studies reflecting the protective role of coffee against mild cognitive impairment and AD, there is insufficient longitudinal evidence corroborating the effect of coffee intake on distinct cognitive domains, and attributable neuropathological pathways that could substantiate such effects. [Nutrition 2016;32:628-636; Arch Med Sci 2017;13:507-514; Clin Nutr 2017;36:730-736]

To assess the relationship between self-reported habitual coffee consumption and cognitive decline, 227 cognitively normal older adults (average age 69.7 years, 60 percent female) were evaluated over a period of 126 months in the AIBL* study. Subgroup analysis looked into the association between habitual coffee intake and cerebral Ab-amyloid accumulation (n=60) and brain volume atrophy (n=51). [Front Aging Neurosci 2021;13:744872]

Over 126 months, habitual coffee intake was positively associated with the cognitive domains of executive function (p=0.006), attention (p=0.044), and AIBL PACC** (p=0.003).

“[These findings imply that] higher coffee consumption was associated with slower cognitive decline, specifically in the executive function and attention domains,” said the researchers. “Furthermore, higher consumption of coffee was also associated with slower decline in the AIBL PACC, which has previously been shown to reliably measure the first signs of cognitive decline in at-risk cognitively normal populations.” [JAMA Neurol 2014;71:961-970]

Moreover, higher coffee consumption was associated with lower risk of transitioning from cognitively normal to mild cognitive impairment or AD status (p=0.006).

Higher coffee consumption was also associated with slower Ab-amyloid accumulation (p=0.017), and a lower likelihood of progressing to ‘moderate’, ‘high’, or ‘very high’ cerebral Ab-amyloid burden status (p=0.035). Conversely, no association was observed between coffee intake and rates of brain volume atrophy (p=0.138, 0.964, 0.713, and 0.624 for cortical grey matter, white matter, left hippocampal, and right hippocampal volumes, respectively).

“Our results further support the hypothesis that habitual coffee intake may be a protective factor against AD,” said the researchers. “[I]ncreased coffee consumption [may reduce] cognitive decline by slowing cerebral Ab-amyloid accumulation, thus attenuating the associated neurotoxicity from Ab-amyloid-mediated oxidative stress and inflammatory processes.”

A modifiable lifestyle factor?

Preclinical evidence suggest that the observed benefits of coffee are not due to caffeine alone. Crude caffeine, which is a by-product of the decaffeination process, has been shown to have neuroprotective effects. [Food Chem 2012;135:2095-2102] Other coffee components that have been shown to have neuroprotective benefits are cafestol, kahweol, and eicosanoyl-5-hydroxytryptamide. [Toxicol Appl Pharmacol 2008;226:328-337; Neurobiol Aging 2014;35:2701-2712]

Further clinical studies are thus warranted to ascertain the benefits from these coffee constituents, and to establish other possible components that could explain for the neuroprotective benefits of coffee. Further trials could also ascertain whether coffee consumption may be considered a modifiable lifestyle factor that could delay the onset of AD.

“[B]locking of adenosine receptors by caffeine, [which leads] to a decrease in Ab-amyloid in the brain, and subsequent reduction of tau hyperphosphorylation is a potential mechanism that also warrants further investigation,” they added.