Neuroprotective Effects of Wine Polyphenols in Alzheimer’s and Parkinson’s Diseases: A Review of Risks and Benefits

Abstract

Neurodegenerative diseases are characterized by the irreversible and progressive loss of nerve cell function, leading to gradual cognitive decline. These diseases often result in a deterioration in quality of life and a shortened lifespan. The most common neurodegenerative diseases in humans are Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis. The recent growing interest is due to the increasing incidence of these diseases and the lack of effective therapeutic methods that could prevent them. However, bioactive compounds contained in foods and beverages have been found to play a significant role in this respect. In particular, a growing body of reports suggests the inverse relationship between wine consumption and the development of such diseases. The main components of wine include ethyl alcohol and polyphenolic compounds (obviously, on a different scale). Wine polyphenols exhibit antioxidant and anti-inflammatory effects. Some of them may cross the blood–brain barrier and then affect the functioning of neurons and other cells. Such activity is considered to be an important factor in the prevention of neurodegenerative diseases related to inflammation, oxidative stress, and mitochondrial dysfunctions. The review presents the current knowledge on the impact of wine consumption and its components on the development of neurodegenerative diseases.

1. Introduction

In recent decades, an average human life expectancy has steadily increased, resulting in a growing proportion of elderly individuals and a corresponding rise in the incidence of neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) in the population. In the overall U.S. population, approximately 10.9% of people aged 65 and older have Alzheimer’s disease, with the percentage of people with AD being 5.0% of those aged 65–74, 13.2% of those aged 75–84, and 33.4% of those aged 85 and older [1]. In the EUROPARKINSON study, a significant portion of undiagnosed Parkinson’s disease cases were identified through screening, with 18% found in the 65–70 age group and 36% in the 80–85 age group. A study in East Boston, Massachusetts, revealed that over 50% of adults over 85 had undiagnosed Parkinson’s disease [2]. These disorders are marked by progressive functional decline, and current therapeutic approaches remain largely symptomatic. Consequently, there is substantial scientific interest in identifying modifiable risk factors, including those related to diet. Among the various dietary patterns examined, the Mediterranean diet has garnered particular attention, in part due to moderate wine consumption. The incorporation of wine into this dietary model, along with the phenomenon known as the “French paradox”, has stimulated research into its potential health effects, especially those associated with its bioactive compounds, most notably polyphenols [3]. What is important is that wine contains ethanol, a substance associated with an increased risk of several diseases, including cancer. However, polyphenols found in wine, particularly resveratrol, are thought to exert beneficial effects in humans, and recent studies reported their neuroprotective properties [4]. Both in vitro and animal studies have provided evidence supporting the ability of these compounds to counteract neurodegenerative processes [4], thereby offering a rationale for investigation into the role of moderate wine consumption in the prevention of neurodegenerative diseases in humans.

The objective of this study was to conduct a critical literature review and explore current research on the relationship between wine consumption and the risk of developing neurodegenerative disorders, specifically Alzheimer’s and Parkinson’s diseases. The emphasis was placed on the particular polyphenolic compounds present in wine, their bioavailability, and their effects on molecular mechanisms involved in neurodegeneration.

2. Overview of Neurodegenerative Diseases

Neurodegenerative diseases comprise a group of disorders characterized by the progressive and irreversible degeneration of neurons, resulting in a gradual decline in both cognitive and motor functions, as well as a significant reduction in quality of life and life expectancy [5,6]. A hallmark of these diseases is the accumulation of specific misfolded proteins that contribute to neuronal dysfunction and death. The most common neurodegenerative disorders include Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). In humans, the incidence of these diseases increases markedly with age, rising approximately ninefold between the ages of 65 and 80. In recent years, the prevalence of neurodegenerative diseases has grown in tandem with rising life expectancy, and the number of affected individuals is projected to increase substantially in the coming decades [7,8,9]. AD is the most prevalent neurodegenerative disorder [1,10], characterized by progressive neuronal loss and a decline in neurotransmitter levels, particularly acetylcholine. The pathophysiology of AD is associated with the accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles, along with the presence of dystrophic neurites. Amyloid plaques are primarily composed of aggregated beta-amyloid (Aβ) peptides, whereas neurofibrillary tangles consist of abnormally hyperphosphorylated tau protein [11]. According to the amyloid cascade hypothesis, the accumulation of Aβ peptides triggers a series of neurodegenerative processes that ultimately lead to neuronal dysfunction and cell death [12]. AD typically presents with a gradual onset. Early symptoms often include mood disturbances, short-term memory loss, and impaired learning ability [1,13]. As the disease advances, patients may experience more severe impairments such as long-term memory loss, aphasia, disorientation, and neuropsychiatric symptoms including depression, anxiety, delusions, and aggression [14,15]. Age is the most significant risk factor for AD. However, other contributing factors include genetic predispositions—most notably the presence of the apolipoprotein E ε4 (ApoE-ε4) allele—and various environmental and lifestyle influences. These include exposure to air pollution, high-fat diets, nutritional deficiencies, central nervous system infections, and comorbid conditions such as diabetes, obesity, atherosclerosis, stroke, and hypertension [8,13,16,17,18,19,20,21,22]. Parkinson’s disease is the second most common neurodegenerative disorder [2], characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra leading to reduced dopamine production. This neuronal loss occurs at a rate approximately 8–10 times higher than that observed in normal aging [16,23,24]. Elevated concentrations of iron ions and hydrogen peroxide in PD contribute to dopamine autoxidation, resulting in the generation of toxic byproducts. Additionally, the intraneuronal accumulation of misfolded proteins, particularly α-synuclein and ubiquitin, leads to the formation of Lewy bodies—a pathological hallmark of PD [25,26]. The primary motor symptoms of PD include bradykinesia, resting tremors, muscular rigidity, and reduced muscle strength. As the disease progresses, patients often develop postural instability and gait abnormalities. PD is also associated with a range of non-motor symptoms, including cognitive decline, dementia, autonomic dysfunction, anosmia, and sleep disturbances such as REM sleep behavior disorder [27]. Other clinical features that aid in diagnosis include hypomimia (reduced facial expressivity), micrographia (progressively smaller handwriting), and a characteristic shuffling gait [28,29]. Aging is the most significant risk factor for PD. However, several other contributors have been identified, including genetic mutations—most notably in the SNCA gene, which encodes α-synuclein—chronic neuroinflammation, oxidative stress, and exposure to environmental toxins such as pesticides. Conversely, potential protective factors include nicotine use, coffee, and moderate alcohol consumption, and also regular physical activity [8,16,17,30]. Although neurodegenerative diseases differ in clinical presentation, they share several core pathophysiological mechanisms. These include the misfolding of amyloidogenic proteins into toxic oligomers and fibrils, which contribute to and are exacerbated by oxidative stress and mitochondrial dysfunction. These processes result in excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [31,32,33]. Oxidative stress arises when the production of free radicals exceeds the capacity of antioxidant defenses. This imbalance leads to the overproduction of ROS such as superoxide anion (O₂•⁻) and hydroxyl radical (•OH), which damage lipids, proteins, DNA, and regulatory molecules. The brain is especially vulnerable due to its high oxygen consumption, high content of polyunsaturated fatty acids, and relatively low levels of antioxidant enzymes. ROS-induced neuronal damage contributes to functional decline and cell death. The body counteracts oxidative stress through antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In addition to these endogenous defenses, dietary bioactive compounds—especially polyphenols—can reduce oxidative damage via antioxidant activity and metal ion chelation [31,32,33]. Neuroinflammation also plays a central role in neurodegeneration by disrupting intracellular signaling and intensifying oxidative stress. Chronic inflammation in the central nervous system (CNS) activates glial cells—primarily microglia and astrocytes. These cells can release pro-inflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitric oxide (NO), proteases, and/or anti-inflammatory agents like interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) [34,35,36]. The phenotypic plasticity of glial cells allows them to shift between protective and harmful states, influencing the progression of inflammation and neurodegeneration. Astrocytes are also crucial in maintaining CNS homeostasis through energy supply, blood flow regulation, and sustaining blood–brain barrier integrity. Studies of patients with mild cognitive impairment (MCI) who progressed to AD revealed elevated TNF-α and reduced TNF-β levels in cerebrospinal fluid, compared to those individuals who did not develop AD [31,32,37]. The brain’s high demand for mitochondrial energy makes it particularly vulnerable to mitochondrial dysfunction—a central element in neurodegenerative disease pathology. Mitochondrial ROS overproduction overwhelms detoxification systems and damages cellular components, leading to death due to apoptosis [38]. Mitochondrial DNA mutations and impaired respiratory chain function further accelerate aging and degeneration. In neurodegenerative diseases, this dysfunction is often marked by reduced activity of respiratory chain enzymes and deficiencies in key electron transport chain complexes, which are essential for oxidative phosphorylation [32].

3. Chemical Composition of Wine

Wine is a non-distilled alcoholic beverage typically produced from grapes through a yeast-driven fermentation process. One of its primary components is ethanol, which generally constitutes between 5% and 13% v/v. Ethanol exerts a biphasic effect on the CNS, while low to moderate doses may offer neuroprotective benefits such as modulating signaling pathways and reducing oxidative stress. Chronic or excessive alcohol consumption is linked to the progression of neurodegenerative processes. These harmful effects include increased production of ROS, mitochondrial dysfunction, microglial activation, impaired neurogenesis, and cognitive decline [39,40].

Each type of wine possesses a unique composition of phenolic compounds, polysaccharides, organic acids, volatile compounds, water, and other compounds. Among these constituents, polyphenols are of particular interest due to their well-documented antioxidant and anti-inflammatory properties. The primary polyphenols found in wine include flavonoids—such as flavanols, flavonols, and anthocyanins—as well as non-flavonoids, including phenolic acids, tannins, and stilbenes (Figure 1). The polyphenol content of wine is influenced by several factors, including grape variety, ripeness, and winemaking techniques, as well as environmental and agricultural conditions such as soil type, climate (including thermal amplitude and precipitation), and viticultural practices [41]. Notably, red wines contain substantially higher levels of polyphenols compared to white wines, primarily because red wine is fermented in the presence of grape skins and seeds, which are rich in polyphenolic compounds [7,31,33,42].

The main polyphenols found in wine include flavanols, which represent the most reduced form of flavonoids. Their concentration in wine typically ranges from 20 to 100 mg/L, with catechin being one of the predominant compounds in this group [41]. Wine is also a notable source of flavonols, which naturally occur in plants primarily as glycosides. In grapes, flavonols are concentrated in the skin, and their levels in grape wines can reach up to 200 mg/L [33]. The primary flavonols present in wine include quercetin, myricetin, and kaempferol [41]. Among all phenolic compounds found in wine, the most extensively studied is resveratrol (3,4′,5-trihydroxystilbene), a member of the stilbene group. Its concentration in wine can reach up to 15 mg/L, with an average of approximately 7 mg/L [31]. Red wines contain significantly higher levels of resveratrol than white wines, owing to its predominant localization in grape skins and the prolonged skin contact during red wine fermentation. Resveratrol has been shown to possess anti-inflammatory, antioxidant, anti-aging, and cardioprotective properties. It is capable of scavenging both ROS and RNS. Notably, catechin, quercetin, and resveratrol are all able to cross the blood–brain barrier—a critical feature in the context of neurodegenerative disease prevention and treatment [31,33,44,45]. The absorption and bioavailability of polyphenols is a complex, multi-step process. Most polyphenols reach the duodenum in an unaltered form; however, only a fraction—primarily aglycones and certain glycosides—is absorbed in the small intestine [46]. The remaining compounds, including esters, polymers, and glycosides, pass into the large intestine, where they are hydrolyzed by colonic microbiota into simpler metabolites that can be absorbed into the bloodstream [47]. Polyphenol absorption in the colon is generally less efficient than in the small intestine, due in part to the colon’s smaller absorptive surface area. Once absorbed into enterocytes, polyphenols undergo phase II conjugation reactions such as methylation, sulfonation, or glucuronidation, which increase their hydrophilicity and facilitate systemic circulation [48]. These conjugated metabolites enter the bloodstream, where they bind primarily to plasma proteins—most notably albumin—and are transported to various tissues throughout the body. Polyphenols are excreted predominantly via the urinary route, but also through the biliary system [49]. Those excreted in bile may re-enter the duodenum and undergo further microbial metabolism followed by reabsorption, a process known as enterohepatic recirculation. The remainder is eliminated in the feces [33,50]. The bioavailability of polyphenols is a critical determinant of their biological activity, particularly with respect to their effects on the nervous system and potential neuroprotective properties. Although resveratrol exhibits relatively low bioavailability, multiple in vivo studies have demonstrated its beneficial effects in humans. This paradox may be partially explained by the biological activity of its metabolites, the potential reconversion of resveratrol glucuronides and sulfates into the active parent compound at target tissues, and enterohepatic recirculation, which prolongs its systemic presence [31,51]. Animal studies have shown that polyphenols such as catechin, epicatechin, and gallic acid, when consumed repeatedly, enter the bloodstream and accumulate in brain tissue [31,52]. Human studies have further demonstrated that regular red wine consumption results in detectable plasma levels of catechin and epicatechin metabolites [53,54]. These findings suggest that consistent polyphenol intake is necessary to maintain adequate plasma concentration for biological effects, including antioxidant and neuroprotective actions. However, polyphenol bioavailability is generally limited and influenced by several factors, including chemical structure (e.g., free vs. glycosidically bound forms), interactions with other dietary components, individual variability in gut microbiota composition, and metabolic transformations occurring in the intestine and liver. As a result, the in vivo biological activity of polyphenols may differ significantly from outcomes observed in vitro, highlighting the need for further research to elucidate their preventive and therapeutic potential [31,53,55]. Dietary components consumed alongside polyphenols—such as alcohol—may also influence their absorption. Alcohol has been shown to enhance polyphenol solubility, thereby potentially increasing absorption. Animal studies have demonstrated that ethanol can augment the absorption of quercetin; however, the concentrations required exceed those achievable through typical dietary alcohol consumption. Human pharmacokinetic studies comparing plasma concentrations of catechin and its metabolites after the consumption of alcoholic vs. non-alcoholic red wine have generally found no significant differences in systemic availability [56]. Interestingly, a modest (~20%) increase in urinary excretion of catechin and its metabolites was observed following the intake of alcoholic wine. While the mechanism behind this observation is not fully understood, one plausible explanation is the diuretic effect of ethanol, which may enhance renal elimination [50,54,57]. However, this finding should be interpreted with caution, as it does not necessarily reflect differences in absorption or bioavailability, and may instead be related to alcohol-induced changes in fluid balance or renal function. Given the rich polyphenol content of wine and its inclusion in dietary patterns such as the Mediterranean and Mediterranean-DASH diets, there is a strong rationale for further investigation into the role of wine consumption in modulating the risk of neurodegenerative diseases in humans [8,58,59,60].

4. Potential Neuroprotective Mechanisms

Polyphenols exhibit neuroprotective effects through their antioxidant and anti-inflammatory properties, their ability to modulate cellular signaling pathways, and their anti-amyloid activity [31]. The antioxidant activity of polyphenols involves the scavenging of free radicals such as reactive oxygen and nitrogen species, thereby protecting cells and tissues from damage. Key mechanisms include regulation of redox-sensitive transcription factors, inhibition of pro-oxidant enzymes, and activation of antioxidant enzymes. Additionally, polyphenols exert beneficial effects on mitochondrial function [31,33,61,62]. In a study using lymphocytes derived from both healthy individuals and those with Alzheimer’s disease, resveratrol was shown to reduce ROS levels, increase the expression of antioxidant enzymes (e.g., catalase), and upregulate anti-aging factors such as sirtuin 1 (SIRT1, silent-mating type information regulation 2 homolog 1) and sirtuin 3 (SIRT3) [61,62]. An in vivo study in gray mice demonstrated that oral administration of resveratrol at a dose of 200 mg/kg body weight/day led to a transient increase in oxidative stress levels, followed by a gradual reduction with age [61,63]. A human study showed that red wine consumption led to increased activity of antioxidant enzymes in the blood, including catalase and superoxide dismutase—key enzymes in the prevention of oxidative stress-related diseases [61,64]. The anti-inflammatory properties of polyphenols are primarily associated with regulation of pro-inflammatory gene expression and cytokine secretion—specifically, suppression of pro-inflammatory cytokines and promotion of anti-inflammatory cytokine production. Polyphenols also influence the function of various immune cells [42]. Numerous in vitro and in vivo studies indicate that resveratrol intake leads to reduced systemic inflammation. In an in vitro model using hippocampal astrocyte cultures from Wistar rats, resveratrol enhanced enzymatic antioxidant defenses by increasing glutathione levels and glutamine synthetase activity. It also significantly decreased levels of pro-inflammatory cytokines such as TNF-α and IL-1β, which are typically elevated in neurodegenerative diseases [61,65]. In vivo study further demonstrated that resveratrol exerts neuroprotective effects in aged mice by attenuating cognitive deficits induced by lipopolysaccharide (LPS) administration and by inhibiting LPS-induced increases in IL-1β levels both in plasma and in the hippocampus. These findings suggest that resveratrol may modulate inflammatory responses in the central nervous system, thereby protecting cognitive function during neuroinflammatory processes [66]. At the cellular level, the neuroprotective effects of polyphenols are linked to their ability to modulate specific signaling pathways. Polyphenols may exert either inhibitory or stimulatory effects on signaling cascades involved in cellular stress responses, including those related to oxidative stress, inflammation, and mitochondrial dysfunction. This modulation may lead to changes in protein phosphorylation states and regulation of genes involved in cell survival, apoptosis, inflammation, and repair mechanisms [31]. Among wine-derived polyphenols, resveratrol is a well-characterized molecule which modulates multiple signaling intracellular pathways. It regulates inflammatory responses through multiple mechanisms, including the arachidonic acid (AA) pathway and the nuclear factor-kappa B (NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway. Figure 2 provides a schematic overview of the main signaling pathways influenced by wine-derived polyphenols, such as NF-κB, Nrf2, SIRT1/3, and COX-2, highlighting their potential contribution to neuroprotection in AD and PD. Within the AA pathway, resveratrol has been shown to inhibit cyclooxygenase (COX) activity, resulting in reduced prostaglandin synthesis. This mechanism is significant, as prostaglandins are key mediators of inflammation and pain. Some studies suggest that resveratrol acts as a more potent inhibitor of COX-2 than COX-1, which is particularly relevant for its specific anti-inflammatory effects, since COX-2 inhibition leads to reduced production of pro-inflammatory prostaglandins [45]. Multiple studies [42,45] confirmed that resveratrol inhibited the activation of NF-κB, resulting in decreased production of pro-inflammatory cytokines such as IL-1, IL-2, IL-6, and TNF-α. Quercetin has also been shown to suppress the expression of inflammation-related genes and to inactivate the NF-κB pathway, thereby reducing the secretion of pro-inflammatory cytokines.

The figure summarizes key neuroprotective mechanisms, including antioxidant and anti-inflammatory effects, modulation of mitochondrial function, inhibition of amyloid aggregation, and regulation of major signaling pathways (e.g., NF-κB, Nrf2, SIRT1/3, COX-2), with emphasis on resveratrol and quercetin. The figure was created using elements from Canva (www.canva.com, accessed on 2 August 2025), under Canva’s content license.

Polyphenols found in wine also possess potent anti-amyloidogenic properties. Their ability to inhibit the formation of amyloid aggregates occurs through several mechanisms, including the stabilization of non-toxic native forms of amyloidogenic proteins and the inhibition of early stages of protein aggregation. Additionally, polyphenols can interfere with fibril growth, promote fibril disassembly into non-toxic species, and prevent amyloid-membrane interactions [31]. In particular, some studies have investigated the effects of wine polyphenols on the formation of toxic amyloid aggregates. Using in vitro models, Caruana et al., 2016 [31] have shown that quercetin inhibits β-amyloid fibril formation and destabilizes preformed fibrils. Furthermore, a metabolite of quercetin—quercetin-3-O-glucuronide—prevented the formation of neurotoxic oligomeric β-amyloid species. Resveratrol is another polyphenol capable of interfering with toxic amyloid aggregation. It has been shown to directly bind to β-amyloid, thereby preventing its aggregation. Studies on Parkinson’s disease have also demonstrated that wine-derived polyphenols such as gallic acid, myricetin, ferulic acid, kaempferol, epicatechin, and catechin inhibit the formation of α-synuclein fibrils and destabilize preformed fibrils [31].

5. Wine Components and Their Beneficial Effects—Review of In Vivo Studies

The assessment of wine consumption in relation to the development of neurodegenerative diseases such as AD and PD is based on results from in vitro and in vivo studies, as well as epidemiological analyses involving human populations [31]. In an in vivo mouse model study, red wine consumption was shown to result in less impairment of spatial memory compared to mice that consumed either water or ethanol. Additionally, reductions in amyloidogenic peptides Aβ1-40 and Aβ1-42 were observed, along with a lower incidence of beta-amyloid plaques in the brains of mice that consumed red wine compared to those given ethanol. The study also demonstrated that moderate wine consumption promotes non-amyloidogenic processing of amyloid precursor protein (APP), which may delay or inhibit the formation of amyloidogenic β-amyloid—a key factor in cognitive decline. However, to confirm the beneficial effects of wine consumption in preventing neurodegenerative diseases, well-designed human studies are essential [31,67]. A study conducted by Orgogozo et al., 1997 [68] reported an approximately fivefold reduction in dementia risk among individuals consuming 3–4 servings of wine per day (250–500 mL), compared to non-drinkers [Odds Ratio (OR) = 0.19, 95% CI: 0.05–0.66]. When focusing specifically on Alzheimer’s disease, a significant reduction in risk was also noted among those consuming 3–4 servings of wine daily (OR = 0.28, 95% CI: 0.08–0.99), with a similar but less pronounced protective effect in individuals consuming 1–2 servings per day (OR = 0.55, 95% CI: 0.31–0.99) relative to abstainers. However, the consumption of more than four servings per day did not show any protective effect against either dementia or Alzheimer’s disease [68,69,70]. Similar findings were reported by Lindsay et al., 2002 [71] who demonstrated that regular wine consumption (at least once per week) was associated with a nearly 50% reduction in the risk of developing AD (OR = 0.49, 95% CI: 0.28–0.88). A similar association was observed with general alcohol consumption, which was also correlated with a lower risk (OR = 0.68, 95% CI: 0.47–1.00). The analysis also included beer and spirits, but no significant protective effects were observed for these beverages with respect to AD risk reduction. In a study conducted by Fischer et al., 2018 [72], higher red wine consumption was associated with a lower incidence of Alzheimer’s disease [Hazard Ratio (HR) = 0.92, 95% Confidence Interval (CI): 0.85–0.99]. Interestingly, the protective effect was observed only in men (HR = 0.82, 95% CI: 0.74–0.92), whereas in women a higher red wine intake was associated with an increased risk of AD (HR = 1.15, 95% CI: 1.00–1.32). No significant association was found between white wine consumption and AD risk in the general population. However, among APOEε4 allele carriers, higher intake of white wine was linked to an increased incidence of the disease (HR = 1.21, 95% CI: 1.01–1.46) [72]. Given that wine contains alcohol, it is also important to consider the potential role of alcohol itself in Alzheimer’s disease risk. Several other studies [7,39,73] have shown that alcohol consumption is associated with a 29% reduced risk of dementia (HR = 0.71, 95% CI: 0.53–0.96) and a 42% reduced risk of AD (HR = 0.58, 95% CI: 0.38–0.89) compared to abstainers. A dose–response analysis indicated that the lowest risk of dementia (HR = 0.40, 95% CI: 0.17–0.94) and AD (HR = 0.13, 95% CI: 0.02–0.95) was observed among individuals consuming 20–29 g of alcohol per day. Neither lower nor higher alcohol intake produced a similar protective effect. Comparable findings were reported by Deng et al., 2006 [74] who found that low alcohol consumption was associated with a reduced risk of both dementia (HR = 0.52, 95% CI: 0.32–0.85) and AD (HR = 0.63, 95% CI: 0.55–0.72) compared to non-drinkers. Furthermore, moderate wine intake specifically was linked to a lower risk of dementia (HR = 0.68, 95% CI: 0.50–0.92) relative to non-wine consumers. These effects were not observed with high levels of alcohol or wine consumption. Some studies have also investigated whether wine consumption affects the progression rate of Alzheimer’s disease after diagnosis. Heymann et al., 2016 [75] reported a slower cognitive decline among both abstainers and individuals consuming one to seven alcoholic drinks per week, compared to those who consumed higher amounts. The slowest rate of cognitive decline was observed in the group of moderate drinkers (1–7 drinks per week). Additionally, the study found that higher consumption of spirits was associated with faster cognitive deterioration, whereas no such association was observed for wine or beer consumption. As previously discussed, resveratrol is one of the key bioactive compounds in wine implicated in neuroprotective mechanisms. Further research has aimed to clarify its role specifically in Alzheimer’s disease. For example, a randomized controlled trial investigating the impact of low-dose resveratrol supplementation on AD progression reported a trend toward reduced cognitive decline in the treatment group compared to placebo. Although the difference did not reach statistical significance, these findings may indicate a modest neuroprotective potential warranting further investigation [76]. Higher doses of isolated resveratrol were used in a study conducted by Turner et al., 2015 [77] in which individuals with mild to moderate AD received at least 500 mg of resveratrol daily. After 52 weeks of supplementation, participants in the resveratrol group showed a smaller decline in Aβ40 concentrations in cerebrospinal fluid and blood serum, as well as a milder deterioration in daily functioning compared to those in the placebo group. These findings suggest that resveratrol may exert neuroprotective effects in the clinical setting. In the context of Parkinson’s disease, one of the earliest studies found a significant inverse association between wine consumption and PD risk. Compared to individuals who abstained from wine, those who consumed one to four bottles of wine per month had a significantly lower risk of developing PD (OR = 0.38, 95% CI: 0.20–0.68), with an even greater reduction observed in those who consumed two to six bottles monthly (OR = 0.25, 95% CI: 0.11–0.56) [78]. Similar results were reported in the Italian FRAGMP study, which demonstrated a reduced risk of PD among wine consumers compared to non-consumers (OR = 0.62, 95% CI: 0.44–0.86). A dose–response trend was also observed: individuals consuming 1–2 glasses of wine per day had a significantly lower risk of PD (OR = 0.68, 95% CI: 0.47–0.97) compared to abstainers, while those consuming at least 3 glasses daily exhibited an even greater risk reduction (OR = 0.45, 95% CI: 0.28–0.74) [79]. Liu et al., 2013 [80] conducted a prospective cohort study as part of the NIH-AARP Diet and Health Study, involving over 300,000 adults aged 50–71 years. The aim of the analysis was to investigate the association between overall alcohol consumption, types of alcoholic beverages (wine, beer, and spirits), and the risk of developing Parkinson’s disease. Over the observation period, no significant association was found between total alcohol intake and PD risk. However, a trend toward reduced risk was observed among individuals consuming 1–2 servings of wine per day compared to abstainers (OR = 0.74; 95% CI: 0.53–1.02), although this result did not reach statistical significance. While these findings suggest a possible inverse association between moderate wine consumption and PD risk, the absence of statistical significance and the observational nature of the study limit the ability to infer causality. Other confounding factors and self-reported alcohol intake may also have influenced the observed trends, underscoring the need for further well-controlled prospective studies. Despite the lack of a demonstrated association between alcohol consumption and Parkinson’s disease risk in the study discussed, meta-analyses confirm the existence of such a relationship [81,82,83]. One of the most recent meta-analyses, conducted by Shao et al., 2021 [81], suggests that moderate alcohol consumption is associated with a reduced risk of developing Parkinson’s disease (RR = 0.81; 95% CI: 0.70–0.95) when compared to the lowest level of intake. The relationship between alcohol intake and PD risk was U-shaped, with the most pronounced protective effect observed at a consumption level of 26–35 g/day. Importantly, further increases in alcohol intake did not result in additional risk reduction, indicating that excessive consumption is not beneficial. When analyzing the impact of wine consumption specifically, no significant association was found with PD risk [81]. Given its high polyphenol content, regardless of alcohol presence, wine has been of interest in the context of the potential role these compounds play in the prevention of PD. Gao et al., 2012 [84] showed that higher flavonoid intake was associated with a lower risk of PD in men. Specifically, a statistically significant 40% reduction in risk was observed among men consuming the highest amounts of flavonoids (quintile 5) (HR = 0.60, 95% CI: 0.43–0.83) compared to men consuming the lowest amounts (quintile 1). No such association was found in women. The study also assessed the impact of wine consumption as a rich source of flavonoids. Interestingly, although wine is a major dietary source of flavonoids, the study found no significant association between wine consumption itself and the risk of PD. This discrepancy suggests that factors other than flavonoid content—such as alcohol or lifestyle variables associated with wine consumption—may influence the observed outcomes. It also highlights the complexity of dietary patterns and the need for caution when interpreting the effects of individual foods or beverages in isolation. Another study evaluated the impact of polyphenols on the progression of already diagnosed PD. It was found that higher flavonoid intake before diagnosis was associated with lower mortality risk in men. The strongest effect was observed among individuals consuming the highest amounts of flavonoids (quartile 4), where the risk was significantly lower (HR = 0.53; 95% CI: 0.39–0.71) compared to individuals consuming the lowest amounts (quartile 1). No similar association was observed in women. Furthermore, it was shown that consuming at least three servings of wine per week before diagnosis was associated with a lower mortality risk (HR = 0.68, 95% CI: 0.51–0.91) compared to those consuming less than one serving per week. An analysis of wine consumption after PD diagnosis revealed that consuming at least three servings per week was associated with a reduction in mortality risk (HR = 0.60, 95% CI: 0.42–0.85) compared to those consuming less than one serving per week [85]. Mischley et al. [86] demonstrated a significant correlation between wine consumption frequency and the rate of Parkinson’s disease progression, measured using the Patient-Reported Outcomes in Parkinson’s Disease (PRO-PD) scale. The PRO-PD scale encompasses over 30 motor and non-motor symptoms, with total scores exceeding 1000 in advanced stages; lower scores indicate milder symptom severity. Each additional unit increase in wine consumption frequency was associated with an average 14.6-point lower PRO-PD score, suggesting a potential protective effect of wine in slowing disease progression. However, this relationship is likely non-linear, and excessive alcohol intake carries known health risks. The study also considered other dietary components and supplements, with statistical models accounting for potential confounders to partially isolate the effect of wine consumption. Nonetheless, due to the observational design, residual confounding cannot be ruled out, and further research is needed. A detailed overview of the epidemiological evidence linking wine consumption to neurodegenerative disease risk is provided in

Table 1. (A) Impact of wine and alcohol consumption on the risk of AD and dementia. (B) Impact of wine and polyphenol intake on risk and progression of PD.

(A)
Type of Alcohol	Amount/Frequency	Effect	Observations	Reference
red wine	3–4 servings/day	↓ risk of AD and dementia	protective effect lost above 4 servings/day	[68]
wine (general)	≥once per week	↓ risk of AD	general alcohol: OR = 0.68 (0.47–1.00); no effect for beer or spirits	[71]
red and white wine	higher intake	♂: ↓ AD risk ♀: ↑ AD risk	white wine increased risk in APOEε4 carriers	[72]
alcohol (general)	20–29 g alcohol/day	lowest risk of AD and dementia	U-shaped dose–response	[7,39,73]
wine/alcohol	low/moderate intake	↓ risk of AD and dementia	no protective effect at high intake	[74]
alcohol (general)	1–7 drinks/week	↓ cognitive decline rate	spirits associated with faster decline; wine and beer neutral	[75]
resveratrol (supplement)	≥500 mg/day for 52 weeks	↓ decline in Aβ40 and daily functioning	suggesting potential neuroprotective effects	[77]
resveratrol (low dose)	–	trend toward ↓ cognitive decline	difference not statistically significant	[76]
(B)
Type of Alcohol	Amount/Frequency	Effect	Observations	Reference
red wine	1–4 bottles/month	↓ risk of PD	dose-dependent effect	[78]
wine	1–2 glasses/day	↓ risk of PD	–	[79]
alcohol (general)/wine	1–2 servings wine/day	trend to ↓ PD risk (not significant)	large cohort; self-reported intake	[80]
alcohol (general)	26–35 g alcohol/day	greatest ↓ risk of PD	U-shaped relationship; no effect for wine	[81]
flavonoids (diet)	quintile 5 vs. 1	↓ PD risk in men	no direct association with wine	[84]
wine (pre/post diagnosis)	≥3 servings/week	↓ mortality risk	no effect at <1 serving/week	[85]
wine	increased frequency	↓ PD progression (PRO-PD score)	observational; adjusted for confounders	[86]

A (AD and dementia) and Table 1B (PD).

6. Dangers of Drinking Wine

While certain bioactive compounds in wine, such as polyphenols, have been associated with potential health benefits, it is imperative to acknowledge that wine contains ethanol, a well-established neurotoxic and addictive agent. Chronic ethanol exposure has been robustly linked to an elevated risk of multiple adverse health outcomes, including carcinogenesis [87], cardiovascular pathology, hepatic injury, and neuropsychiatric disorders [88,89,90]. Despite epidemiological data suggesting possible protective effects of moderate wine consumption, authoritative bodies such as the World Health Organization [91] and the American Cancer Society [92] consistently maintain that no amount of alcohol consumption can be considered completely safe. Therefore, alcohol intake should not be advocated as a prophylactic intervention. Moreover, the addictive potential of ethanol and individual contraindications, including pre-existing medical conditions and medication interactions, necessitate cautious evaluation before recommending wine consumption in clinical practice.

7. Conclusions and Future Perspectives

Several observational studies have suggested a potential association between low to moderate wine consumption and a reduced risk of developing neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. This potential protective effect is believed to be partly attributable to the presence of bioactive compounds in wine, particularly polyphenols. Moderate red wine intake is traditionally associated with the Mediterranean diet—a dietary pattern widely acknowledged for its positive impact on brain health. In this context, wine is considered as just one component of a broader lifestyle that emphasizes high consumption of vegetables, fruits, whole grains, legumes, fish, nuts, and olive oil, while limiting processed foods and added sugars. Given the well-established health risks associated with alcohol, there is growing interest in the potential health effects of non-alcoholic wine. Since polyphenols are present in wine irrespective of its alcohol content, research into non-alcoholic wine offers an opportunity to examine the potential neuroprotective effects of these compounds without the confounding and harmful influence of ethanol. Further investigation is warranted to clarify whether non-alcoholic wine can confer similar neurological benefits and to better understand the role of polyphenols in neurodegenerative disease prevention.