Key Information
Purpose
According to a WHO statement, it has been asserted that there is no safe level of alcohol consumption regarding human health. Nevertheless, the relationship between alcohol consumption and Alzheimer’s disease (AD) pathology remains unclear. Therefore, we examined whether the frequency and patterns of alcohol consumption could predict neurodegeneration biomarkers in a cohort of middle-aged adults without dementia.
Methods
A total of 195 participants without dementia were included from the ALBION study. Multivariate logistic regression analyses were conducted using drinking frequency subgroups (abstainers, occasional drinkers, and light-to-moderate drinkers) and Mediterranean-Alcohol Dietary Pattern (MADP) adherence subgroups along with cerebrospinal fluid (CSF) AD biomarkers (Tau, phosphorylated tau (PTau) and amyloid beta (Aβ). In these analyses, the abstinence was used as the reference category.
Results
Of the 195 individuals without dementia, 66% were female, with an average age of 65 ± 9.4 years, and they had 13.8 ± 3.6 years of education. Logistic regression analyses revealed that light-to-moderate drinkers (n = 51) were associated with higher Aβ positivity [OR: 2.98 (1.29–6.90)] compared to the abstinence (n = 117). Additionally, high adherence to the MADP was significantly associated with higher Aβ, Tau/Aβ42, and PTau/Aβ42 ratios positivity compared to the abstinence.
Conclusion
Light-to-moderate alcohol intake was associated with higher Aβ deposition in middle-aged individuals without dementia, compared to abstinence. High adherence to the MADP, which indicates low-to-moderate red wine consumption distributing over the week with meals, was associated with a higher Aβ and Tau/Aβ and PTau/Aβ positivity. Therefore, the management of alcohol consumption may help improve AD outcomes even at the preclinical stage.
Keywords: Alcohol consumption, Mediterranean-alcohol dietary pattern, Alzheimer’s disease, Amyloid beta, Cerebrospinal fluid, Neurodegeneration biomarkers
Introduction
In accordance with a statement issued by the World Health Organization (WHO) in January 2023, it has been asserted that there is no safe level of alcohol consumption in terms of human health [1external link, opens in a new tab]. A Paneuropean study conducted in 2021 concluded that the consumption of alcohol at a light to moderate level (1–2 drinks per day) was responsible for 23,300 new cases of cancer [2external link, opens in a new tab]. However, on the opposite side, it has been argued that the health effects of alcohol are significantly influenced by the quantity consumed, and the drinking patterns. As an example, there is evidence indicating that consuming certain alcoholic beverages in low amounts, along with meals or in specific patterns such as the Mediterranean-Alcohol Dietary Pattern (MADP), may have potential benefits for cardiovascular health [3external link, opens in a new tab–5external link, opens in a new tab]. In any way, excessive alcohol consumption leads to conditions such as alcoholic liver disease, malnutrition, pancreatitis, brain diseases, and fetal alcohol spectrum disorder in cases of alcohol-use disorder [6external link, opens in a new tab].
When it comes to cognitive effects, it is well-established that chronic, heavy alcohol consumption causes alcohol-related brain damage [7external link, opens in a new tab] and cognitive deficits [8external link, opens in a new tab, 9external link, opens in a new tab]. With respect to moderate alcohol consumption, observational studies often report a J-shaped relationship between alcohol consumption and cognitive outcomes, including specific and all-cause dementias; low-to-moderate alcohol consumption is often associated with a lower risk of dementia compared to abstention and heavy drinking [10external link, opens in a new tab]. Specifically, meta-analyses of studies involving older adults, both prospective and case-control, indicate that low or even moderate levels of alcohol consumption among older individuals may reduce the risk of cognitive decline and Alzheimer’s disease (AD), revealing a non-linear dose-response relationship between alcohol intake and the risk of AD [11external link, opens in a new tab–17external link, opens in a new tab].
There are several pathways through which alcohol consumption may affect cognitive function. Alcohol may induce aberrant activation of cell death through various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons, individually or in combination, have been observed in the AD [18external link, opens in a new tab]. Pathological hallmarks of AD include primarily the accumulation of two proteins: Amyloid beta (Aβ) peptides and abnormally phosphorylated tau (PTau) proteins [19external link, opens in a new tab, 20external link, opens in a new tab]. These protein aggregates result in the formation of Aβ plaques and neurofibrillary tangles [21external link, opens in a new tab, 22external link, opens in a new tab], respectively, and induce neuroinflammation and neurodegeneration over years, leading to a multitude of cognitive and behavioral deficits [23external link, opens in a new tab]. Monitoring Aβ levels can serve as an early indication of the onset of AD [24external link, opens in a new tab], and the identification of factors that have the potential to influence Aβ, Tau and PTau levels may pave the way for future recommendations in the prevention and treatment of AD [25external link, opens in a new tab]. Various environmental factors, such as healthy eating habits [26external link, opens in a new tab], adequate sleep [27external link, opens in a new tab] and high activity levels [28external link, opens in a new tab], may delay the Aβ accumulation.
With respect to alcohol consumption, there are limited and conflicting data regarding its association with the accumulation of Aβ [26external link, opens in a new tab]. A cross-sectional study including 806 participants, published in 2021, indicated that moderate alcohol consumption (≥ 1 times/week) may have a detrimental influence on cerebrospinal fluid (CSF) AD biomarkers (Aβ burden, Tau/Aβ, and PTau/Aβ ratios) compared to the light drinking (> 0 times/week and < 1 times/week) [29external link, opens in a new tab]. Conversely, previous cross-sectional studies, with smaller sample sizes, indicated that moderate alcohol consumption may have a beneficial influence on Aβ burden in individuals without dementia [30external link, opens in a new tab, 31external link, opens in a new tab]. Lastly, two cross-sectional and one cohort study reported that there was no significant correlation between alcohol consumption and Aβ and/or Tau and PTau deposition [25external link, opens in a new tab, 32external link, opens in a new tab, 33external link, opens in a new tab]. In summary, the existing observational studies examining the association between CSF AD biomarkers and alcohol consumption are limited and have produced mixed results. In addition, none of these observational studies examined other parameters of alcohol consumption, apart from frequency, such as drinking patterns, including the type of alcohol, whether alcohol consumed with or without meals, the distribution of alcohol consumption over the week or overall alcohol consumption patterns.
Therefore, the aim of this cross-sectional study was to examine whether alcohol consumption is associated with CSF neurodegeneration biomarkers (Aβ burden, Tau/Aβ and PTau/Aβ ratios) in middle-aged adults without dementia. We conducted an analysis of alcohol consumption utilizing two distinct metrics, namely (i) frequency of alcohol consumption and (ii) the MADP.