I'm doing it to increase my healthspan, lower my chances of dementia and Parkinsons.
If you provide research that tells me 3-4 cups a day reduces dementia and Parkinson's risk, then I'll change my habit, but until then this is occurring:
Research suggests caffeine is not the main reason for these other benefits, go ask your incompetent doctor for clarification.
Like Your Coffee Black? Congratulations, You Could Be a Psychopath I need to add milk
How coffee protects against Parkinson’s Aug. 2014
Coffee May Lower Your Risk of Dementia Feb. 2013
Coffee drinkers rejoice! Drinking coffee could lower the risk of Alzheimer’s disease
And this: Coffee's Phenylindanes Fight Alzheimer's Plaque December 2018
New research suggests drinking coffee may reduce the risk of frailty May 2025
I think I'm in this category: I never get
the jitters or flushed skin.
Genetics determine how much coffee you can drink before it goes wrong
I'm doing a 12 cup pot of coffee a day with full fat milk to lessen my chances of dementia and Parkinsons. Tell me EXACTLY how much coffee to drink for that and I'll change. Yep, that is a lot more than the 400mg. suggested limit, I don't care! Preventing dementia and Parkinsons is vastly more important than whatever problems it can cause!
The latest here:
Caffeine in Aging Brains: Cognitive Enhancement, Neurodegeneration, and Emerging Concerns About Addiction
by 
,,, and
Manuel Glauco Carbone
1,2,3,Giovanni Pagni
4,Claudia Tagliarini
5,Icro Maremmani
2,3,* andAngelo Giovanni Icro Maremmani
2,31
Division of Psychiatry, Department of Medicine and Surgery, University of Insubria, Viale Luigi Borri 57, 21100 Varese, Italy
2
VP Dole Research Group, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy
3
Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy
4
Department of Psychiatry, North-Western Tuscany Local Health Unit, Tuscany NHS, Lunigiana Socio-Sanitary Area, Piazza Craxi 22, 54011 Aulla, Italy
5
Psychiatric Diagnosis and Treatment Service (S.P.D.C.), Sant’Elia Hospital, Provincial Health Authority 2, Via Luigi Russo 6, 93100 Caltanissetta, Italy
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2025, 22(8), 1171; https://doi.org/10.3390/ijerph22081171
Submission received: 20 June 2025 / Revised: 18 July 2025 / Accepted: 21 July 2025 / Published: 24 July 2025
(This article belongs to the Section Behavioral and Mental Health)
Abstract
This narrative review examines the effects of caffeine on brain health in older adults, with particular attention to its potential for dependence—an often-overlooked issue in geriatric care. Caffeine acts on central adenosine, dopamine, and glutamate systems, producing both stimulating and rewarding effects that can foster tolerance and habitual use. Age-related pharmacokinetic and pharmacodynamic changes prolong caffeine’s half-life and increase physiological sensitivity in the elderly. While moderate consumption may enhance alertness, attention, and possibly offer neuroprotective effects—especially in Parkinson’s disease and Lewy body dementia—excessive or prolonged use may lead to anxiety, sleep disturbances, and cognitive or motor impairment. Chronic exposure induces neuroadaptive changes, such as adenosine receptor down-regulation, resulting in tolerance and withdrawal symptoms, including headache, irritability, and fatigue. These symptoms, often mistaken for typical aging complaints, may reflect a substance use disorder yet remain under-recognized due to caffeine’s cultural acceptance. The review explores caffeine’s mixed role in neurological disorders, being beneficial in some and potentially harmful in others, such as restless legs syndrome and frontotemporal dementia. Given the variability in individual responses and the underestimated risk of dependence, personalized caffeine intake guidelines are warranted. Future research should focus on the long-term cognitive effects and the clinical significance of caffeine use disorder in older populations.
1. Introduction
The consumption of caffeine among the elderly represents a complex issue that warrants careful and nuanced examination. While it is acknowledged that caffeine intake can confer certain benefits, it is equally important to evaluate potential risks and the heightened sensitivity that this age group may develop. Caffeine is not solely found in coffee; it is also present in tea, chocolate, energy drinks, and even in some pharmaceuticals, which contributes to its widespread exposure across populations [1,2]. For the purposes of clarity and consistency in this review, we will use the term “elderly people” to refer to individuals aged 65 years or older, a definition that aligns with criteria commonly used by the World Health Organization (WHO) and in numerous studies in the field of geriatrics. It is important to acknowledge, however, that a universally accepted definition of “elderly” does not exist, and that the studies included in this review may employ varying age-based inclusion criteria (e.g., 60 years and older). We recognize that this variability could be a limitation when interpreting and comparing research findings.
In older adults, the metabolism of caffeine tends to slow, leading to prolonged biological half-life and amplification of its effects, thus necessitating a cautious approach to consumption [3].
A key factor contributing to this prolonged half-life is the age-related decline in metabolic rate. However, compromised renal function can further impair the clearance of caffeine metabolites, exacerbating this effect in older adults. Supporting the influence of genetic factors and their association with kidney function, recent research [4,5] has confirmed these relationships. Furthermore, a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES)—a nationally representative survey assessing the health and nutritional status of adults and children in the United States—by Gao et al. (2025) [6] highlighted an inverse association between the consumption of coffee, tea, and caffeine and the presence of CKD, further reinforcing the potential protective role of these dietary habits on renal health.
Moderate caffeine intake has generally been associated with cognitive benefits in elderly individuals, including improvements in short-term memory, attention, and verbal fluency [7,8,9]. Nonetheless, with advancing age, sensitivity to caffeine appears to increase, consequently elevating the risk of adverse effects [10]. These include sleep disturbances, heightened anxiety, gastrointestinal issues, cardiovascular problems, and an increased likelihood of developing osteoporosis [11,12,13,14,15]. Moreover, age-related decline in renal function, coupled with reduced hydration status and potential interactions with polypharmacy, may exacerbate adverse outcomes related to caffeine consumption [16,17,18].
Therefore, a careful assessment of caffeine intake is essential in elderly populations, considering individual health conditions, comorbidities, and medication regimens to balance potential benefits against risks accurately. An often underestimated aspect is the potential for dependence; even in late adulthood, habitual consumers may develop caffeine dependence, with abrupt reduction potentially provoking withdrawal symptoms, such as headaches, fatigue, and irritability [19,20,21].
The prevalence of caffeine consumption among older adults is considerable and warrants attentive awareness from healthcare professionals. Epidemiological studies have demonstrated that a significant proportion of individuals over 65 years consume caffeine regularly [22,23,24]. For instance, a 2018 survey conducted by the National Sleep Foundation reported that approximately 40% of Americans aged between 65 and 79, and about 35% of those aged 80 and above, consume caffeine on a daily basis [25,26,27]. Although research specifically targeting caffeine dependence in older populations remains limited, some evidence suggests that the risk of developing dependence may increase with age, particularly after 60 years [21,28,29,30,31]. This trend could be attributed to factors like decreased metabolic rate and physiological changes in body composition, which may render older adults more susceptible to the stimulating effects of caffeine [32,33].
Caffeine consumption is also widespread within the Italian elderly population, although data indicate that prevalence decreases with age [34]. A survey by the Italian National Institute of Statistics revealed that around 70% of Italians aged between 65 and 74 drink coffee daily [35]. Notably, compared to US figures, Italians tend to consume higher quantities of caffeine overall [36,37]. Nonetheless, it appears that elderly Italians may have a lower propensity to develop caffeine dependence compared to their American counterparts, possibly due to cultural differences in consumption patterns and genetic factors influencing caffeine metabolism [21,38,39,40]. It is important to acknowledge that environmental factors, particularly climate and humidity, can influence renal capacity and hydration, potentially impacting caffeine metabolism [41,42]. While these factors may contribute to population-level differences in caffeine sensitivity, definitive evidence remains limited.
To further elucidate individual variability, we considered research on genetic variations influencing caffeine metabolism. Studies have shown that CYP1A2 rs762551 AC/CC genotypes (associated with slower caffeine metabolism) are linked to increased risks of albuminuria, hyperfiltration, and hypertension with high coffee intake [43], supporting a genetic predisposition. These findings align with research demonstrating that CYP1A2 polymorphism impacts athletic performance [44,45], suggesting a broader influence on individual responses to caffeine. The interplay between climate, genetics, and individual factors likely shapes the complex response to caffeine, highlighting the need for personalized recommendations.
This narrative review aims to critically examine the role of caffeine in brain health among older adults, with a focus on its pharmacological mechanisms, cognitive and motor effects, potential neuroprotective properties in neurodegenerative diseases, and the often-overlooked issue of dependence. By integrating findings across diverse neurological domains, this review seeks to inform clinical awareness and public health strategies for safe and personalized caffeine consumption in later life.
2. Review Results
This narrative review presents an integrated synthesis of current evidence regarding the effects of caffeine on brain health in older adults. The findings are organized into thematic sections to reflect the most clinically and biologically relevant domains.
First, the pharmacokinetic and pharmacodynamic characteristics of caffeine are reviewed, with particular attention to age-related changes that influence its absorption, metabolism, and action on adenosine, dopamine, and glutamate systems. These mechanisms underpin both the stimulant effects of caffeine and its potential to induce tolerance and dependence.
The review then explores the neurobiological basis of caffeine dependence, including receptor adaptations and withdrawal syndromes, which remain under-recognized in elderly populations. Following this, the role of caffeine in various neurological and neurodegenerative conditions is assessed. In movement disorders, such as Parkinson’s disease and essential tremor, as well as in conditions like multiple sclerosis and Tourette’s syndrome, caffeine shows a spectrum of effects ranging from potentially protective to symptom-aggravating depending on dose, disease type, and individual sensitivity.
Attention is also given to caffeine’s influence on cognitive domains, including memory, attention, and executive function, as well as its debated role in age-related cognitive decline. Finally, the review evaluates emerging evidence of caffeine’s impact on major neurodegenerative diseases, including Alzheimer’s disease, vascular dementia, frontotemporal dementia, and Lewy body dementia.
Together, these results highlight a complex and sometimes contradictory profile of caffeine in later life, necessitating a personalized and cautious approach to its use.
2.1. Effects of Caffeine on the Brain: Pharmacokinetics and Pharmacodynamics
Caffeine, a psychoactive compound classified within the methylxanthine group, is widely consumed for its stimulant properties. Its pharmacological activity is intrinsically linked to its trajectory within the body, from absorption to elimination. The absorption of caffeine occurs rapidly, primarily through the gastrointestinal tract, with plasma concentrations reaching their peak approximately 30 to 60 min post-ingestion. Once in circulation, caffeine rapidly disseminates across tissues, including the central nervous system, due to its ability to cross the blood–brain barrier. The hepatic metabolism of caffeine plays a central role, principally mediated by the enzyme CYP1A2, a member of the cytochrome P450 system. This process generates active metabolites, including paraxanthine, theobromine, and theophylline, which contribute to the overall psychoactive effects. Renal excretion is the main pathway for the elimination of caffeine and its metabolites, with the half-life varying significantly among individuals due to factors like age, hepatic and renal function, smoking, and concurrent medication use [46,47,48,49]. In older adults, significant pharmacokinetic changes occur that warrant special attention. Hepatic metabolism, primarily through CYP1A2, declines with age, leading to slower clearance of caffeine [50,51,52,53]. Studies have shown that the half-life of caffeine can increase from 3–5 h in young adults to 6–10 h or more in older adults [19,54]. Reduced renal function further impairs the excretion of caffeine metabolites, prolonging their presence in the body [3,4,11,55]. Consequently, the same dose of caffeine can result in higher plasma concentrations and a greater risk of adverse effects in older adults.
As previously said, it is essential to underscore that individual response to caffeine is highly subjective and can be influenced by genetic predispositions, such as variants of the CYP1A2 gene, as well as physiological states, including pregnancy and aging [50,55,56,57]. In particular, aging-related changes can prolong caffeine’s half-life and heighten susceptibility to adverse effects, underscoring the importance of personalized consumption guidelines [46]. Therefore, healthcare providers should consider these age-related pharmacokinetic changes when recommending caffeine intake to older adults, carefully assessing potential interactions with medications and existing health conditions [2,58].
Caffeine exerts its primary pharmacodynamic effects mainly through antagonism of adenosine receptors in the central nervous system. Adenosine, an inhibitory neurotransmitter, accumulates during wakefulness, promoting relaxation and preparing the brain for sleep. Structurally similar to adenosine, caffeine binds to these receptors without activating them, functioning as a competitive antagonist. This blockade reduces the inhibitory influence of adenosine, thereby increasing arousal, alertness, and cognitive performance. Caffeine exhibits high affinity particularly for the A1 and A2A adenosine receptor subtypes [59,60,61].
The antagonism of A1 receptors, predominantly located in the hippocampus, cerebral cortex, and basal ganglia, facilitates the release of excitatory neurotransmitters, such as dopamine, acetylcholine, and glutamate. These mechanisms help explain caffeine’s stimulant effects on cognitive functions, mood, and vigilance [62,63,64,65,66]. Meanwhile, blocking A2Areceptors, mainly expressed in cerebral vasculature and the striatum, contributes to caffeine’s vasoconstrictive properties and influences motor control. Moreover, inhibition of A2Areceptors in the striatum enhances dopamine release, underpinning caffeine’s rewarding properties and its potential for dependence [67,68,69,70,71,72,73].
Beyond direct receptor interaction, caffeine modulates dopaminergic and cholinergic systems by increasing dopamine release and inhibiting its reuptake at the synaptic level, largely via antagonism of A2Areceptors [74,75,76]. The resultant elevation of dopaminergic activity in the striatum, a key brain area involved in motivation, reward, and executive function, contributes to enhanced mood, motivation, and cognitive performance [77,78]. However, this same mechanism also underpins the development of tolerance and dependence.
Additionally, caffeine influences the cholinergic system by promoting the release of acetylcholine in several brain regions, including the prefrontal cortex and the hippocampus. This effect is mainly mediated by the inhibition of A1 adenosine receptors and plays a significant role in facilitating cognitive processes, such as attention, learning, and memory [11,49].
2.2. Neurobiological Mechanisms of Caffeine Dependence: From Neurotransmitter Systems to Motor and Cognitive Circuits
Chronic caffeine consumption induces neuroadaptive changes that lead to tolerance and dependence. The brain, continually exposed to caffeine’s antagonistic effects on adenosine receptors, activates compensatory mechanisms to preserve homeostasis. One such mechanism is receptor down-regulation, characterized by a reduction in the number of adenosine A1 and A2Areceptors on neuronal cell surfaces. This decrease diminishes the brain’s sensitivity to caffeine’s effects, necessitating higher doses to achieve the same stimulating response. Such adaptation underpins the development of tolerance, whereby increasing amounts of caffeine are required to produce desired effects [79,80,81,82].
Abrupt cessation or significant reduction of caffeine intake following prolonged habitual use can precipitate withdrawal symptoms [83]. This occurs because the suppression of adenosine’s inhibitory action is no longer present, leading to a rebound effect. Withdrawal symptoms typically expressed are listed below.
Headache: Adenosine acts as a vasodilator; caffeine’s vasoconstrictive effect contributes to headaches upon discontinuation due to sudden vasodilation.
Manifestations of caffeine dependence in the elderly may present unique challenges for clinical identification. While the core withdrawal symptoms remain consistent with younger populations, their presentation can be masked or misinterpreted due to the higher prevalence of comorbid conditions and age-related physiological changes [85,87,88,89]. For instance, fatigue, a common withdrawal symptom, can be easily attributed to the natural aging process or underlying medical conditions, such as anemia, endocrinopathies, or different metabolic disorders [90]. Similarly, headaches may be dismissed as tension headaches or attributed to medication side effects [91,92]. Irritability and anxiety may be misconstrued as symptoms of various neuropsychiatric disorders, including primary anxiety disorders, mood disorders, or early manifestations of a neurodegenerative condition [93,94].
Furthermore, the cognitive enhancing effects of caffeine can lead to a cycle of dependence, with older adults using caffeine to counteract age-related cognitive decline or fatigue, unknowingly perpetuating their dependence. This can make it difficult to distinguish between caffeine withdrawal symptoms and underlying cognitive impairment.
Clinical identification of caffeine dependence in the elderly requires a thorough assessment, including a detailed history of caffeine intake, a careful evaluation of other potential causes for their symptoms, and a high index of suspicion. Questionnaires designed to assess caffeine dependence, such as the Caffeine Use Disorder Questionnaire (CUDQ), may be useful in identifying problematic caffeine use [95], but their validity in older adults needs further investigation. Clinicians should also be aware of the potential for underreporting of caffeine consumption due to social stigma or lack of awareness [96,97].
Given the potential for misdiagnosis and the negative impact of caffeine dependence on health outcomes, clinicians should consider routine screening for caffeine use and dependence in older adults, particularly those presenting with unexplained fatigue, anxiety, or cognitive complaints. Strategies to manage caffeine dependence in older adults include gradual caffeine reduction, behavioral therapies, and management of comorbid conditions [21,98].
While caffeine does not directly bind to dopaminergic receptors, it indirectly activates the brain’s reward circuits, particularly the mesolimbic dopamine pathway. Originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens, amygdala, and prefrontal cortex, this system mediates feelings of pleasure, motivation, and associative learning [75]. Caffeine’s blockade of A2Aadenosine receptors in the striatum enhances dopamine release in the nucleus accumbens, producing pleasure and positive reinforcement that contribute to repeated consumption and dependence development.
The rewarding and cognitive-enhancing effects of caffeine are largely mediated through the increased release of excitatory neurotransmitters, including dopamine, acetylcholine, and glutamate, via the antagonism of adenosine receptors [99]. This mechanism explains caffeine’s efficacy in improving vigilance, attention, memory, and executive functions. However, this stimulatory effect can become self-perpetuating, as dependence develops as individuals seek to maintain optimal cognitive performance, fostering a vicious cycle. Tolerance to caffeine’s cognitive effects may drive increased intake, culminating in dependence and withdrawal symptoms, such as headache, fatigue, and irritability, upon attempts to reduce consumption [100].
Long-term habitual caffeine intake may lead to significant neurophysiological alterations, with potential negative consequences for cognitive function and motor control. Prolonged caffeine exposure induces down-regulation of adenosine receptors, resulting in modifications across several brain regions described below [65,77,101].
- Prefrontal cortex (PFC): The PFC is critical for executive functions, working memory, decision making, and attention. The PFC shows increased activity initially with caffeine due to elevated levels of dopamine and acetylcholine. Chronic use, however, can lead to dopamine receptor down-regulation, impairing cognitive efficiency, reducing cognitive flexibility, and increasing impulsivity.
Amygdala: Involved in emotion regulation, particularly fear and anxiety, caffeine may augment amygdala activity, heightening stress responses and anxiety, especially in predisposed individuals. Chronic use may contribute to hyperactivity of this region, exacerbating anxiety and irritability, notably during caffeine withdrawal.
Striatum: Caffeine influences motor control primarily through antagonism of A2Areceptors in the striatum, a pivotal structure in voluntary movement regulation [102,103,104,105,106]. Persistent caffeine intake can cause desensitization of dopaminergic receptors in the striatum, diminishing its initial positive effects on motor coordination. Manifestations may include decreased movement precision, tremors, impaired coordination, and slowed reaction times.
Cerebellum: This structure, integral for fine motor coordination, balance, and motor learning, may also be affected indirectly by caffeine-induced dopaminergic alterations, potentially contributing to deficits in balance and coordination. Although direct studies are limited, the neuroadaptive changes in dopaminergic pathways suggest that long-term caffeine consumption could subtly impair motor functions.
In summary, sustained caffeine intake can induce widespread alterations in neural activity across multiple brain regions, with potential adverse effects on cognitive and motor functions. It is crucial to recognize that individual sensitivity to caffeine, dosing patterns, and duration of use significantly modulate these neurophysiological responses, emphasizing the importance of personalized assessment and cautious consumption in vulnerable populations.
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