Abstract
Emerging evidence suggested that impairments in sensory function (e.g., vision, hearing, taste, smell, touch, and somatosensation) may be linked to the increased risk of late-life cognitive disorders, dementia, and Alzheimer's disease (AD). Among sensory changes, age-related gustatory function plays a critical role in appetite regulation and nutritional status, altering dietary patterns and leading to inadequate nutrient intake and an increased frailty risk, particularly oral frailty. This novel frailty phenotype showed an abnormal oral structure and/or decline in multi-faceted oral function and coexisting decline in physical and cognitive functions. In the present review article, we discussed the intricate interplay among gustatory dysfunction, oral frailty, and AD, addressing also possible underlying mechanisms. In AD, gustatory dysfunction was differentially associated with the severity of cognitive deficits. In AD patients, worse threshold scores and overall taste identification (particularly for sour) were found compared to controls, along with worse overall scores, sweet, and sour scores compared to subjects with mild cognitive impairment. Periodontal disease and number of teeth (two key indicators of oral frailty) were consistently associated with late-life cognitive impairment/decline and dementia, particularly AD. Although the mechanisms are unclear, gustatory dysfunction and oral frailty may increase the risk of cognitive disorders/AD through increased brain atrophy or impacts on social isolation, psychological well-being, or oral health. Understanding the associations among gustatory dysfunction, oral frailty, and AD may be critical for developing comprehensive strategies to preserve sensory and oral function, and for prevention, earlier diagnosis, and holistic management of patients with or at risk for AD.
Keywords
Introduction
Aging is associated with a progressive decline in sensory and physiological functions, significantly impacting overall health and quality of life. 1 Vision, hearing, smell, taste, touch, and somatosensation may mediate our interaction with the world and contributed uniquely to our understanding of the environment and ourselves. 2 Social isolation, loneliness and chronic stress may promote late-life cognitive and psychiatric disorders and, in a vicious circle, sensory deficits (vision, hearing, olfaction, taste, and somatosensation). 2 In particular, sensory changes, particularly hearing and vision impairments, are dementia-modifiable risk factors as suggested by an exploratory workshop of the National Institute on Aging, concluding that sensory and motor changes may anticipate the cognitive symptoms of Alzheimer's disease (AD) by several years, significantly increasing AD risk.3,4 Very recently, the 2024 update of the Lancet Commission on dementia identified peripheral age-related hearing loss, untreated vision loss, and social isolation as potentially modifiable dementia risk factors. 5 Among sensory changes, gustatory function—the ability to detect and distinguish taste stimuli—plays a critical role in appetite regulation and nutritional status. 6 Age-related deterioration in gustatory function can alter dietary patterns, leading to inadequate nutrient intake and an increased risk of frailty in older adults. 7 Frailty, a clinical syndrome marked by diminished strength, endurance, and physiological reserves, is linked to adverse health-related outcomes, including sarcopenia, heightened susceptibility to illness, and increased mortality risk. 8 Individuals with AD were particularly vulnerable to the combined effects of gustatory dysfunction, malnutrition, and oral frailty, a particular multifactorial phenotype of frailty involving declines in mastication, swallowing function, and overall oral health, further accelerating functional deterioration.9–11
Gustatory dysfunction, defined as a reduced ability to perceive taste stimuli, is prevalent among aging populations due to structural and functional changes in the peripheral and central gustatory pathways. 1 Contributing factors included taste bud atrophy, altered salivary composition, and neurodegenerative processes affecting the gustatory cortex and insular regions. 12 Additionally, multimorbidity, such as diabetes mellitus and hypertension, along with pharmacological treatments commonly prescribed to older adults, may further impair taste perception. 13 The diminished ability to detect key taste modalities—particularly bitter, sour, and umami—can reduce the palatability of nutrient-dense foods, fostering a preference for highly processed, energy-dense foods rich in sugar and sodium. Such dietary changes may result in micronutrient deficiencies and inadequate protein intake, both critical contributors to frailty progression. 7 Oral frailty may further exacerbate nutritional deficits in older adults. Age-related factors such as tooth loss, xerostomia, and neuromuscular impairment of the orofacial region can significantly hinder food intake. 14 Additionally, gustatory dysfunction may reduce the sensory feedback essential for effective chewing and swallowing, further diminishing dietary intake and accelerating frailty progression. 15 Frailty itself is characterized by declines in muscle mass, strength, and physical function, increasing the risk of falls, hospitalization, and reduced quality of life. 8 The co-occurrence of gustatory dysfunction and oral frailty has been described as a potential “vicious cycle” (Figure 1), whereby impaired taste perception and poor oral function may contribute to nutritional decline, frailty, and cognitive deterioration.10,14 However, these interactions are highly multifactorial, influenced by systemic inflammation, multimorbidity, psychosocial factors, and health behaviors. Thus, the ‘vicious cycle’ should be regarded as a conceptual framework rather than a comprehensive mechanistic model.
The vicious cycle of gustatory dysfunction, poor nutrition, frailty, and cognitive decline.
In the context of AD, the interplay between gustatory dysfunction, oral frailty, and cognitive impairment is particularly pronounced.10,14 AD pathology, characterized by amyloid-β (Aβ) plaques and tau protein aggregates (neurofibrillary tangles, NFTs), leads to widespread neurodegeneration affecting multiple brain regions, including those involved in gustatory processing. 1 Notably, taste perception deficits have been reported as early manifestations of AD, sometimes preceding overt cognitive impairment. 16 Dysfunction within the insular cortex and other gustatory-related neural networks may contribute to altered taste perception, diminished appetite, and unintentional weight loss. 17 Furthermore, AD progression is associated with impairments in oromotor function and swallowing, increasing the risk of malnutrition and frailty. 18
The interrelationships among gustatory dysfunction, oral frailty, and AD highlighted the need for early identification and targeted interventions to mitigate nutritional decline in aging populations. Understanding these associations may be critical for developing comprehensive strategies to preserve sensory and oral function, optimize nutritional intake, and prevent frailty-related complications. In the present narrative review article, we discussed the intricate interplay among gustatory dysfunction, oral frailty, and AD, addressing also the possible underlying mechanisms. In fact, given the impact of gustatory dysfunction on dietary behaviors and overall health, future research should explore therapeutic approaches, including dietary modifications, oral rehabilitation strategies, and pharmacological interventions, to improve nutritional outcomes and enhance quality of life in older adults, particularly those with AD and other neurodegenerative disorders.
Methods
The present article was a narrative review, nevertheless, to minimize bias and provide transparency, we performed a structured literature search in PubMed, Scopus, and Web of Science databases. The search covered publications from January 2000 to March 2025 using combinations of the following keywords: gustatory dysfunction, taste impairment, oral frailty, aging, Alzheimer's disease, cognitive decline, nutrition, and frailty. Additional relevant articles were identified through manual searches of reference lists. We prioritized peer-reviewed original research articles, systematic reviews, and meta-analyses published in English. Studies were included if they addressed gustatory dysfunction, oral frailty, or their association with aging, frailty, or AD. Exclusion criteria were case reports, non-peer-reviewed articles, conference abstracts, and studies focused exclusively on pediatric or non-human populations. The final selection was based on relevance to the aims of the present narrative review.
Pathophysiology of age-related gustatory dysfunction
As the human body ages, sensory perception undergoes significant changes, including a decline in taste perception, known as age-related gustatory dysfunction. This decline resulted from physiological, cellular, and neural alterations that compromise the integrity of the gustatory system. 19 A primary factor is the gradual degeneration of taste buds and reduced density, particularly in the fungiform papillae on the anterior tongue. While taste buds undergo continuous turnover, aging diminishes the regenerative capacity of taste receptor cells, leading to decreased taste sensitivity. This process is further exacerbated by epithelial atrophy, which may impair signal transduction from tastants to neural pathways.20,21
Salivary composition and flow rate also declined with age, affecting the dissolution and transport of tastants to taste receptors. Saliva contains essential enzymes and proteins facilitating flavor detection, and reduced salivation, often associated with xerostomia (dry mouth), further impairs taste perception. 22 At the molecular level, changes in taste receptor expression contributed to altered taste function. G-protein-coupled receptors (GPCRs) that mediate sweet, umami, and bitter taste signaling undergo age-related downregulation, while ion channels responsible for detecting salty and sour stimuli may exhibit functional alterations. These molecular changes reduced the ability to distinguish subtle flavor differences, often leading to complaints of food tasting bland or having altered intensities.23,24
The decline in taste perception extends beyond peripheral receptors to central gustatory processing pathways. Taste signals are transmitted via the facial, glossopharyngeal, and vagus nerves to the nucleus of the solitary tract in the brainstem. 19 In these pathways, age-related neuronal loss, demyelination, and reduced synaptic efficiency may impair taste signal transmission and integration. In the gustatory cortex, located in the insular and frontal opercular regions, structural and functional changes contributed to deficits in higher-order taste processing, reducing the ability to identify complex flavors.19,25,26 For example, Hoogeveen and colleagues used functional magnetic resonance imaging to compare brain activation in response to basic tastes between young and older adults, revealing altered activation patterns in higher-order taste processing areas among older individuals. 25 Additionally, a randomized clinical trial (RCT) involving 96 participants employed gustatory event-related potentials to examine age-related differences in taste processing. 26 Findings indicated changes in neural signatures within the central nervous system, supporting the notion that aging-related gustatory decline extends beyond peripheral taste bud degeneration to neural circuit alterations. 26
Beyond physiological changes, systemic factors such as chronic inflammation, oxidative stress, and metabolic alterations may contribute to age-related gustatory dysfunction. Elevated inflammatory cytokines and oxidative damage can impair both peripheral and central gustatory structures, further compromising function. 27 Additionally, polypharmacy is common in older adults, with medications such as antihypertensives, antidepressants, and chemotherapeutic agents known to alter taste perception either by directly affecting taste receptors or inducing dry mouth. 28 Neurodegenerative diseases, including AD and Parkinson's disease (PD), further exacerbated gustatory dysfunction by disrupting neural circuits involved in taste perception.1,9,17
Impact of gustatory dysfunction on dietary habits and frailty
Gustatory dysfunction, characterized by impaired taste perception, has significant consequences for dietary habits and overall health, particularly in individuals at risk of frailty. 29 Taste plays a crucial role in food choices, nutrient intake, and appetite regulation. Disruptions in taste perception, whether due to aging, neurological disorders, metabolic diseases, or medication side effects, can lead to dietary changes that often resulted in nutritional deficiencies.30,31 A diminished ability to perceive basic taste modalities (sweet, salty, sour, bitter, and umami) can drive increased consumption of highly palatable but nutritionally poor foods, reducing overall diet quality and quality of life. 32 For instance, individuals with hypogeusia or ageusia may develop a preference for foods high in sugar or salt to compensate for reduced taste sensitivity, potentially worsening conditions such as hypertension, obesity, and diabetes mellitus.33–35 Conversely, dysgeusia, characterized by distorted taste perception, may lead to aversions to nutrient-dense foods, such as fruits, vegetables, and protein sources, further increasing the risk of malnutrition. 36
The link between gustatory dysfunction and frailty is particularly evident in older adults, where gustatory impairment often coincides with olfactory decline, collectively termed chemosensory dysfunction. 37 A cross-sectional analysis of the U.S. National Health and Nutrition Examination Survey (NHANES) 2013–2014 demonstrated that self-reported chemosensory dysfunction was independently associated with frailty measures, suggesting a potential tool for assessing or predicting frailty in older individuals. 37 Frailty, a multidimensional syndrome characterized by reduced physiological reserves, strength, and resilience, is closely linked to inadequate dietary intake and malnutrition. 7 Some studies indicated that individuals with gustatory impairment were more prone to unintended weight loss, sarcopenia, and reduced protein intake, all of which are critical contributors to frailty. 38 However, these associations may also be influenced by confounding variables such as socioeconomic status, multimorbidity, and polypharmacy that have not been consistently taken into account across the studies. Limited dietary diversity, often seen in older subjects with gustatory impairment, exacerbated vitamin and mineral deficiencies, accelerating both physical and cognitive decline. 39 Moreover, gustatory dysfunction may negatively impact psychological well-being, reducing meal enjoyment, social engagement, and overall quality of life.32,40,41 This psychological burden may further discourage adequate nutrition, creating a vicious cycle of frailty and deteriorating health.
Addressing the impact of gustatory dysfunction on dietary habits and frailty requires targeted nutritional interventions and sensory stimulation techniques. Enhancing food palatability through herbs, spices, and umami-rich seasonings can help improve taste perception without excessive sugar or salt intake.42,43 Additionally, texture-modified diets, tailored meal planning, and nutritional counseling can support adequate food intake despite gustatory impairment.44,45 Emerging studies suggested that interventions such as zinc supplementation and taste training therapies may help restore taste function, improving dietary behaviors and reducing frailty-related complications. 46 In particular, a recent systematic review and meta-analysis including 12 RCTs with 938 subjects with idiopathic and zinc-deficient gustatory disorder suggested that the intervention with zinc supplementation found more frequent improvements in gustatory disorder in the experimental group compared to the control group. 46 A holistic approach integrating medical, nutritional, and psychological support may contribute to enhance food enjoyment, maintain nutritional adequacy, and ultimately improve health outcomes for individuals with gustatory dysfunction.
Oral frailty: definitions, causes, and implications
Oral frailty is a relatively new concept in gerodontology and aging research, describing the progressive decline in oral function associated with aging.14,47,48 This construct encompasses impairments in mastication, swallowing, tongue strength, and saliva production, which can lead to difficulties in eating, speaking, and maintaining oral hygiene.14,49,50 In 2013, the concept of oral frailty was first proposed by the Japanese Society of Gerontology and defined as an age-related decrease in oral function, 51 however, the definition of this new construct remained controversial. 52 Table 1 shows the principal conceptual and operational definitions of oral frailty.14,47,48,51–63
Principal conceptual and operational definitions of oral frailty.
A recent concept analysis defined oral frailty as abnormal oral structure and/or decline in multi-faceted oral function and coexisting decline in physical, cognitive, and social functions. 52 The causes were aging, social frailty, and severe periodontal disease, whereas its implications were decline in physical health and mental health, social withdrawal, lower quality of life and systemic frailty. 52 In fact, recognized as an intermediate stage between robust oral health and severe oral disability, oral frailty is increasingly viewed as a significant risk factor for systemic frailty and overall functional decline in older adults. Recent studies highlighted that oral frailty is not merely a localized concern but a key determinant of general adverse health-related outcomes, with strong associations to increased risks of sarcopenia, malnutrition, cognitive decline, and AD.10,14,48,50 Early identification of oral frailty is crucial, as it serves as a predictive marker for broader frailty syndromes and potential disability in older individuals.48,50 However, the lack of a standardized definition of oral frailty represents a major challenge for both research and clinical practice. The existence of multiple, sometimes overlapping, operational criteria has led to substantial variability in prevalence estimates and inconsistent identification of at-risk individuals across studies (Table 1). This definitional uncertainty undermines comparability of findings, limits the ability to pool data in meta-analyses, and complicates the interpretation of longitudinal associations with frailty, cognitive decline, and AD. Moreover, without consensus on diagnostic thresholds, it remains difficult to translate research findings into screening tools or intervention strategies. Greater efforts are therefore needed to achieve harmonization of definitions and standardized assessment protocols to advance both research validity and clinical applicability
The causes of oral frailty are complex and multifactorial, involving physiological, pathological, and behavioral components. 14 Age-related sarcopenia affects the muscles involved in mastication and swallowing, leading to weakened oral motor function and an increased risk of aspiration pneumonia.48,49 Additionally, periodontal disease, tooth loss, and reduced saliva secretion significantly contribute to diminished oral capacity. Key indicators of oral frailty included declines in oral motor skills, chewing and swallowing difficulties, and oral pain, all of which are strongly associated with systemic frailty. 14 Neurological disorders such as dementia and PD further exacerbate oral dysfunction, as cognitive decline impairs an individual's ability to maintain oral hygiene and proper dietary intake.10,64 Moreover, lifestyle factors such as poor oral hygiene, smoking, and a lack of regular dental care accelerate the deterioration of oral function.65,66
The implications of oral frailty extend beyond oral health, profoundly affecting overall well-being and quality of life (Table 1).50,52 Impaired mastication can lead to inadequate nutrient intake, weight loss, and muscle wasting, all of which contribute to physical frailty.14,48 Some studies have also linked poor oral health to a higher risk of hospitalization, functional disability, bone disorders, and even mortality, although factors such as general health behaviors, nutrition, and access to dental care may partially explain these associations.48,50,67 Furthermore, compromised oral frailty indicators may increase the risk of cardiovascular disease, 68 primarily due to chronic inflammation associated with periodontal disease. For example, periodontal disease has been shown to trigger systemic inflammation, which plays a key role in the development of cardiovascular conditions. 68 Similarly, diabetes mellitus is closely linked to oral health, as hyperglycemia worsens gum disease, creating a cycle of systemic inflammation and impaired metabolic control. 69 In addition, individuals with oral frailty were at a heightened risk of respiratory infections, including aspiration pneumonia, due to weakened swallowing mechanisms that allow oral bacteria to enter the airway. 49 Given these connections, addressing oral frailty is not merely linked to the maintenance of oral function but also to the prevention of serious, life-threatening complications. The social and psychological consequences of oral frailty were also significant. Older adults with oral frailty often experienced reduced confidence in social interactions due to difficulties in speaking and eating. This can lead to social isolation, depression, and even cognitive decline, as social engagement serves as a protective factor against neurodegeneration.10,14,52 The bidirectional relationship between oral frailty and systemic frailty underscored the importance of preserving oral function to maintain both physical and mental well-being.
Managing oral frailty requires a multidisciplinary approach that integrates dentistry, geriatrics, nutrition, and speech therapy to develop effective interventions. Regular dental check-ups, oral rehabilitation exercises, speech and swallowing therapy, and the use of dental prosthetics can help preserve oral function.14,49,50,67 Nutritional interventions, including a diet rich in soft but nutrient-dense foods, may help mitigate the effects of oral frailty on overall health. 70 Public health initiatives should also emphasize the importance of lifelong oral hygiene habits to prevent the early onset of oral frailty. Given the increasing global aging population, recognizing oral frailty as a critical health issue may be essential for promoting healthy aging and preventing disability.
The bidirectional relationship between gustatory dysfunction and oral frailty
The bidirectional relationship between gustatory dysfunction and oral frailty resulted in a cascading impact on systemic health, particularly in older age (Figure 1). One key mechanism linking gustatory dysfunction to oral frailty is salivation. Saliva is essential for taste perception, as it dissolves tastants and facilitates their interaction with taste receptors. Hyposalivation, a common feature of oral frailty, leads to impaired gustatory response. Sasano and colleagues demonstrated that treating hyposalivation reduces hypogeusia, underscoring the importance of salivation in maintaining normal taste function. 71 Notably, umami taste stimulation has been shown to enhance salivary flow through the gustatory–salivary reflex. 71 The use of Japanese Kobucha (kelp tea: powdered tangle seaweed) to stimulate umami taste and promote reflexive salivation has yielded improvements in salivation, taste function, appetite, weight, and overall health. 71 Reduced taste sensitivity may also drive dietary modifications, with individuals favoring softer, processed, and often nutrient-poor foods. This shift accelerates masticatory muscle atrophy and exacerbates oral frailty. 72 Furthermore, deficiencies in key micronutrients, particularly zinc, vitamin B12, and iron, which are essential for taste bud maintenance and neural taste transmission, can contribute to both gustatory dysfunction and the deterioration of oral structures.46,73
Conversely, oral frailty itself can precipitate or worsen gustatory dysfunction due to mechanical and neuromuscular decline. The progressive reduction in tongue strength and mobility, characteristic of oral frailty, may impair tastant distribution across the tongue, leading to altered taste perception.14,48,50 Additionally, poor dentition and prosthetic maladaptation can further compromise masticatory efficiency, indirectly affecting gustatory receptor stimulation. 74 Chronic oral inflammation, frequently associated with oral frailty, has also been linked to gustatory disturbances. Conditions such as periodontal disease and oral lichen planus may trigger inflammatory cytokine release, disrupting taste receptor cell renewal and altering neural processing of taste stimuli.75,76
Beyond localized oral effects, the interplay between gustatory dysfunction and oral frailty has broader implications for overall health and quality of life. Gustatory dysfunction is strongly associated with reduced appetite and weight loss, increasing the risk of sarcopenia and systemic frailty.7,25 Malnutrition, a frequent consequence of altered taste perception and gustatory dysfunction, contributes to immune dysregulation, cognitive decline, and heightened susceptibility to infections.15,77 Moreover, gustatory dysfunction has been implicated in neurodegenerative disorders, including PD and AD, both of which are linked to oral frailty.1,10,17,64 Shared pathophysiological mechanisms, such as neuroinflammation and impaired dopaminergic signaling, suggest a potential common pathway that warrants further investigation.
Intervention strategies such as salivary stimulants, dietary modifications, prosthodontic rehabilitation, and neuromuscular training may help break the cycle of deterioration. Additionally, emerging research on taste receptor modulation and regenerative therapies may offer promise in mitigating both gustatory and oral frailty-related impairments. Understanding taste receptor functions beyond the oral cavity, particularly in the gastrointestinal tract, may pave the way for novel interventions aimed at improving metabolic functions and digestion, potentially alleviating aspects of gustatory dysfunction and oral frailty.70,78–80
Gustatory dysfunction and oral frailty in Alzheimer's disease
Gustatory dysfunction and oral frailty in AD significantly impacted overall health and quality of life in affected individuals.1,9,10 AD is marked by cognitive decline, memory loss, and various physical impairments. Among the less commonly discussed consequences were the AD effects on oral health and gustatory function.1,11,16 Gustatory dysfunction, which often presents as hypogeusia or ageusia, and oral frailty—characterized by weakened oral structures and muscles—were prevalent among individuals with AD. These conditions contribute to malnutrition, reduced dietary intake, and a diminished quality of life. 1 9–11,18
A recent systematic review and meta-analysis of studies evaluating gustatory dysfunction in neurocognitive disorders (NCDs) of different severity [mild NDCs (mild cognitive impairment, MCI) and major NCDs (dementia)] and etiologies (AD, PD, vascular dementia, Lewy body dementia, frontotemporal multiple etiologies) found that, despite some discrepancy across studies, patients with NCDs showed overall worse gustatory function than cognitively intact individuals. 9 Moreover, gustatory dysfunction was differentially associated with the severity of cognitive deficits in AD-related NCDs. 9 Finally, in AD patients were also found worse global taste threshold and identification scores (sour in particular) than controls and worse global, sweet, and sour scores compared to MCI. 9 Gustatory dysfunction in AD was commonly associated with neurodegenerative changes in brain regions responsible for taste perception and sensory processing, particularly the gustatory cortex, i.e., the anterior insula on the insular lobe and the frontal operculum on the inferior frontal gyrus of the frontal lobe.12,17 In fact, amygdala, insula, orbitofrontal cortex, and thalamus are key brain regions both for gustatory and cognitive processing. Volume changes in the medial temporal lobe structures including amygdala, hippocampus, entorhinal cortex, and parahippocampal gyrus, have been reported by neuroimaging studies of early AD.81,82 As the disease advances, Aβ plaque accumulation and NFTs disrupted normal sensory processing, resulting in diminished taste perception. This reduction not only decreased the enjoyment of food but may also may lead to disinterest in eating altogether, further reducing nutrient intake.12,17 Impaired taste perception, especially regarding sweetness or saltiness, may result in a preference for highly processed and nutritionally poor foods, exacerbating malnutrition.33–36
Oral frailty in AD patients, though related to gustatory dysfunction, is a distinct condition encompassing difficulties with chewing, swallowing, and maintaining oral hygiene. 10 Cognitive and physical decline associated with AD may impair the coordination of muscles involved in mastication and swallowing. As frailty progresses, individuals often preferred softer, less nutritious foods that require minimal mastication, thereby worsening malnutrition.10,11,83 Additionally, compromised dentition, inadequate dental care, and poorly fitting dentures further reduced masticatory efficiency, negatively impacting both oral health and overall nutrition.10,14,74 Moreover, chronic oral inflammation, frequently observed in AD, also may contribute to gustatory dysfunction. A large systematic review and meta-analysis investigating the impact of periodontal disease, one of the key indicators of oral frailty, on cognitive disorders (cognitive impairment and cognitive decline), dementia, and depression showed that periodontal disease was found to be associated with both cognitive disorders [relative risk (RR) 1.25, 95% confidence interval (CI): 1.11–1.40 for cross-sectional studies/cognitive impairment and RR 3.01, 95% CI 1.52–5.95 for longitudinal studies/cognitive decline) and dementia (RR 1.22, 95% CI 1.10–1.36). 83 Conditions such as periodontal disease can provoke the release of inflammatory cytokines, which impaired taste receptor function, hindering the renewal of taste receptor cells.76,83 Moreover, inflammatory disorders like periodontal disease and oral lichen planus may alter the neural processing of taste stimuli, further aggravating gustatory dysfunction and oral frailty.75,76 This convergence of neurodegeneration and inflammation may create a vicious cycle where poor oral health can exacerbate gustatory dysfunction, leading to further nutritional deficiencies and weight loss.10,76,83
According to a recent meta-analysis, individuals with a higher degree tooth loss, another key indicator of oral frailty, showed a 1.48 times greater likelihood of developing cognitive impairment and a 1.28 times higher risk of being diagnosed with dementia. 84 Furthermore, edentulous individuals were associated with a 1.54-fold increased risk of cognitive impairment and a 1.40-fold higher risk of being diagnosed with dementia. 84 Beyond nutritional implications, gustatory dysfunction and oral frailty profoundly affected mental health and overall well-being.10,40,50 Loss of taste and eating difficulties can lead to depression, anxiety, social isolation, and agitation, 85 as affected individuals may struggle to enjoy meals or participate in social activities involving food.10,86,87
Finally, a very recent large systematic review on 63 studies (56,520,662 subjects) investigated the impact of oral frailty indicators on late-life cognitive disorders and late-life depression (LLD) utilizing 11 oral frailty indicators subdivided in four categories: (i) oral health status deterioration, (ii) decline in oral motor skills, (iii) chewing, swallowing, and saliva disorders, and (iv) oral pain. 88 In this study, four oral frailty indicators (number of remaining teeth, periodontal disease, difficulties in chewing, and difficulties in swallowing) were related with late-life cognitive impairment/decline, MCI, dementia, and LLD. 88 Among categories, oral health status deterioration and chewing, swallowing, and saliva disorders were associated with late-life cognitive impairment/decline, MCI, dementia, and LLD. Decline in oral motor skills was related with late-life cognitive impairment/decline, while oral pain was associated only to LLD. 88
Limitations and confounding factors
The interpretation of the associations summarized in the present narrative review must be approached with caution. Most available studies are observational, and many are cross-sectional, limiting causal inference. Study quality varies, with inconsistent control for confounding variables. Important factors such as socioeconomic status, education, health behaviors (diet, smoking status, physical activity), multimorbidity, polypharmacy, and access to dental and medical care may influence both gustatory/oral function and cognitive outcomes. In many cases, these potential confounders were not systematically adjusted for, raising the possibility of residual biases. Furthermore, heterogeneity in study design, sample size, diagnostic criteria, and methods for assessing taste or oral frailty complicates direct comparisons across studies. Future research should incorporate more rigorous adjustment for confounding variables and employ longitudinal and interventional designs to better clarify these relationships.
Conclusions
In older age, gustatory dysfunction and oral frailty are emerging areas of interest in understanding the complex relationships among oral health and neurodegenerative conditions, particularly AD. Emerging evidence suggested that these conditions are not merely consequences of aging or cognitive decline; instead, they may actively contribute to the pathophysiological processes underlying AD. Disruptions in taste function may lead to reduced dietary intake and malnutrition, which can exacerbate systemic inflammation and neurodegenerative pathways. Additionally, oral frailty, characterized by impaired chewing ability and deteriorating oral hygiene, may worsen cognitive decline through chronic inflammatory responses and reduced sensory stimulation. However, the majority of the current findings were based on observational studies and the proposed mechanistic pathways remained speculative.
Two key indicators of oral frailty (periodontal disease and number of teeth) were consistently associated with late-life cognitive impairment/decline, and dementia, particularly AD. Very recently, using data from a nationally representative sample of U.S. older adults, several associations have been found between periodontal disease and intrinsic capacity, a novel construct encompassing individual's combined physical and mental resources essential for daily functioning across five key domains—locomotion, cognition, vitality, psychological well-being, and sensory function. 89 In particular, severe periodontal disease was associated with reduced locomotion, impaired psychological well-being (depressive symptoms) and sensory function (vision), while moderate periodontal disease was linked to reduced locomotion and impaired sensory function (hearing). 89
Therefore, these preventable oral frailty indicators should be comprehensively managed in individuals with early cognitive dysfunction, underlining the importance of integrating oral health assessments into broader health evaluations for older adults. Moreover, addressing periodontal disease could be a key component in preserving unimpaired cognitive and mental health and enhancing quality of life in older age. The interconnection among oral frailty indicators, late-life cognitive disorders, and AD requires a comprehensive and interdisciplinary approach to care. Robust research, integrated care models, and preventive strategies may be essential for better health outcomes and improved quality of life in subjects with late-life cognitive disorders. By understanding and coordinating care for these conditions, healthcare providers can significantly enhance the well-being and functional status of older adults.
Based on current evidence, several practical steps can be recommended despite existing limitations. First, older adults, particularly those with MCI or early AD, should be considered priority populations for gustatory dysfunction and oral frailty screening. Simple tools such as self-reported gustatory and chewing difficulties, combined with basic oral examinations, can be integrated into comprehensive geriatric assessment and memory clinic evaluation. 90 Second, interventions should be tailored: zinc supplementation may be appropriate for individuals with documented deficiency or idiopathic gustatory disorder, whereas oral frailty may be addressed through dental rehabilitation, prosthetic adjustments, and targeted orofacial exercises. Nutritional counseling, including flavor enhancement strategies (e.g., use of herbs, spices, umami-rich seasonings), should be implemented to mitigate reduced palatability of nutrient-dense foods. Finally, interdisciplinary collaboration between geriatricians, dentists, nutritionists, speech therapists, and neurologists is essential to deliver comprehensive care. Despite these recommendations, evidence remains sparse. Most interventions are supported by small-scale or short-term studies, with heterogeneity in methods and outcomes. Larger, well-controlled RCTs are urgently needed to determine treatment effectiveness, optimal protocols, and long-term benefits for specific patient groups. Until such data are available, clinical strategies should remain pragmatic, patient-centered, and flexible to individual needs.
Currently, research efforts focus on charting clear directions in preventive health care settings to anticipate key adverse health outcomes in AD patients. The bidirectional relationship between gustatory dysfunction and oral frailty may complicate their roles in AD. Impaired taste perception may lower motivation for oral care, while oral frailty may negatively impact both nutritional status and gustatory function. This could create a vicious cycle that accelerates cognitive deterioration and may diminish the quality of life for older adults. Given these findings, integrating assessments of gustatory function and oral frailty into routine geriatric evaluations could help identify individuals at risk for cognitive decline early on. that the majority of current findings are based on observational studies and that proposed mechanistic pathways remain speculative that the majority of current findings are based on observational studies and that proposed mechanistic pathways remain speculative Further longitudinal and interventional studies are needed to clarify the causal mechanisms and validate these oral health markers as predictive tools for AD. Addressing gustatory dysfunction and oral frailty in clinical practice could open new avenues for prevention, early intervention, and management of patients with or at risk for AD.
Footnotes
Author contribution(s)
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This paper was supported by the Project “Development of an ensemble learning-based, multi-dimensional sensory impairment score to predict cognitive impairment in an elderly cohort of Southern Italy” funded by the European Union – Next Generation EU – NRRP M6C2 – Investment 2.1 Enhancement and Strengthening of NHS biomedical research (Grant Agreement PNRR-MAD-2022-12376656)
Declaration of conflicting interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Francesco Panza and Madia Lozupone are Editorial Board Members of this journal but were not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.