Dementia is a progressive neurological disorder in which cognitive decline and impaired daily functioning present significant global health and socioeconomic challenges [1].  In view of the graying of the population, its prevalence is expected to increase dramatically; thus, there is an ever greater need to address this condition in all its multifaceted dimensions. Besides the neurodegenerative implications, often said to be the most characteristic signs of the disease, oral effects of health probably represent a relatively neglected, yet crucial area requiring systematic consideration [2]. Problems with dental hygiene expose patients with dementia to the risk of diseases due to the cognitive, behavioural, and motor impairment issues that characterize the disease and compound the bidirectional relationship between oral and systemic health [3].

The interrelation of oral health with dementia is multifactorial and occurs through numerous mechanisms, including systemic inflammation, alterations in the microbiome, and direct effects from oral diseases on cognitive pathways [4]. Chronic oral conditions such as periodontitis and caries have been considered in the causation of systemic inflammatory states in patients with dementia. These systemic inflammatory states may accelerate neurodegenerative processes by increasing pro-inflammatory cytokines within peripheral circulation and also within the central nervous systems of dementia patients [5]. Furthermore, oral pathogen colonization, including that of Porphyromonas gingivalis, has been implicated in cognitive decline through various mechanisms implicating disruption of the blood-brain barrier, amyloidogenesis, and neuroinflammation [6-8].

Furthermore, the pharmacological interventions to treat dementia result in related side effects such as xerostomia and decreased salivary flow. This further diminishes the oral health of patients [9]. Poor oral hygiene in patients with dementia tends to lead to higher rates of aspiration pneumonia, malnutrition, and reduced quality of life, making it highly critical to provide effective oral care strategies tailored to this vulnerable population. Although the challenges above were considered, there was still so much underexplored ground, especially in oral medicine in dementia care, and the evidence was disjointed about its role in mitigating disease progression or improving outcomes for the patient [10-11].

The emerging evidence suggests that specially designed oral health interventions such as professional dental care, caregiver-assisted oral hygiene practices, and structured oral exercise regimens may benefit patients suffering from dementia through enhanced cognitive performance, prevention of systemic infections, and improved general health outcomes [9-11]. However, study designs, intervention protocols, and outcome measures have been somewhat inconsistent which has limited the generalization of these findings. In addition, oral microbiome modulation as a therapeutic target is still at infancy stage and also deserves further study.

Against such a background, a systematic review is warranted to summarize the existing evidence on oral health in interrelation to dementia and systematically appraise how effective oral medicine is in managing the condition. In that regard, this paper attempts critically to examine the impacts of oral health interventions on outcomes in dementia-affected people, which include measures of cognitive function, quality of life, and systemic health.

Eligibility criteria

The PECOS protocol designed for this systematic review was used to find pertinent literature on the role of oral medicine in the care and treatment of patients suffering from dementia. The protocol followed the reporting guideline for PRISMA [12], which aims at methodologic rigor and transparency. The elements of the protocol were: Population (P) which embraced patients diagnosed with dementia, Exposure (E) embracing interventions connected with oral medicine practices like regular maintenance of oral hygiene, caregiver-assisted oral care with or without exercises involving oral health; Comparator (C) that meant standard care or no oral health intervention at all; Outcomes (O) which included measures such as cognitive function, oral health outcomes, and secondary health-related impacts like the systemic conditions; and the Study Design (S) which embraced clinical trials and cross-sectional studies. On the one hand, clinical trials are selected with a high level of evidence for intervention effects; on the other hand, cross-sectional studies are selected for insight into population-level patterns and associations. The construction of this protocol has helped in identifying, selecting, and evaluating studies comprehensively related to the objectives of the review.

Inclusion and Exclusion Criteria

Clinical trials and cross-sectional studies published in peer-reviewed journals that evaluated patients diagnosed with dementia in terms of the impact of oral medicine interventions. Only interventions would be considered in the form of oral hygiene practices, oral health exercises, or caregiver-assisted oral care. The studies included had to report cognitive outcomes, oral health measures, or related systemic health impacts. Studies published in any geographic location or language were included if a reliable translation into English was available.

Eliminated from consideration were studies not classified as primary research, such as editorials, seminar articles, case reports, and reviews. Studies that did not include oral medicine interventions or studies where participants were not patients with dementia were excluded. Further, studies which deviated from the proposed objectives or did not report outcomes of clinical interest were excluded. There was a rationale behind the selection of clinical trials and cross-sectional studies: high-quality evidence from these trials must be supplemented with broader observational data in order to capture real-world implications.

Database Search Protocol

A systematic search across six databases: PubMed, Scopus, Web of Science, Cochrane Library, Embase, and CINAHL has been performed. Boolean operators and Medical Subject Headings (MeSH) terms were used to develop comprehensive search strings customized to the architecture of each database. The search terms included variations for "oral medicine," "dementia," "oral hygiene," "cognitive outcomes," and "systemic health." Synonyms, truncation, and field-specific operators were used to maximize the sensitivity and specificity of searches (Table 1). Each search was limited to studies up to the time of the search, and study design filters (clinical trials and cross-sectional studies) were applied where appropriate.

Data Extraction Protocol and Data Items

The data extraction process followed a structured and pre-defined protocol. A standardized data extraction form was used to ensure consistency across reviewers. Data items extracted included study details (author, year, country, and study design), participant demographics (sample size, mean age, sex ratio), intervention details (type, frequency, duration), comparator details, outcomes assessed (cognitive, oral health, and systemic health outcomes), statistical measures (effect sizes, confidence intervals, p-values), and follow-up duration. Those inconsistencies at the extraction process were then addressed either through discussion or by consulting a third reviewer.

Bias Assessment Protocol

The RoB 2.0 of Cochrane's tool [13] was used in the assessment of the clinical trials' quality, applying the domains including the randomization process, deviations from the intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. For cross-sectional studies, the AXIS tool [14] was used to appraise methodological quality, focusing on clarity of objectives, sample size justification, selection criteria, risk of non-response bias, and appropriateness of statistical methods. Both tools ensured a systematic and transparent evaluation of the risk of bias, thus enhancing the reliability of the synthesized findings

Initially, the databases were searched and 588 records were identified for retrieval (Figure 1). After removal of 187 duplicate records and another 176 records ineligible for inclusion as identified using automation tools, 223 records proceeded to screening. No records were excluded at initial screening, hence 223 reports sought for retrieval of which 147 reports were not retrieved. Then, 76 reports were screened for inclusion. Out of them, 69 reports were excluded for various reasons, among which 30 were editorials, 26 seminar articles, and 13 studies that departed from their intended objectives. In the end, 7 studies [15-21] were included in the review with no additional reports associated with these studies.

LEGEND

Table 1: Search strings across databases

Study Design and Sample Characteristics

The articles included in the review represented a mix of RCTs and cross-sectional surveys to reflect diverse methodological methods (Table 1). Five studies applied RCT designs involving those conducted in Taiwan [15], China [16], Japan [17, 20], and Thailand [19], while the remaining study was a cross-sectional survey in Germany [18]. The sample sizes would vary extensively in the studies, from relatively small ones like 20 participants in Thailand [19] to large-scale investigations with more than 300 participants in Japan [21]. Generally, the inclusion of RCTs ensured rigorous assessments of the interventions while the cross-sectional survey was able to provide some insight into population-level practices and attitudes.

The selected studies also examined various age groups, ranging from 52.95 ± 10.55 years in Germany [18] to 86.1 years in Japan [20]. Gender distribution was skewed toward more female participants in some of the studies, including an 68:22 male-to-female ratio in Japan [17]. The period of follow-up also varied from one month [20] to 24 months [21], thus facilitating the assessment of short-term and long-term effects.

Table 2: Demographic characteristics assessed

Groups Evaluated and Interventions

The interventions focused on appropriate oral health care practices for dementia patients (Table 3). These included oral health programs conducted before the swallowing training in Taiwan,15 regular oral hygiene with additional interventions conducted in China,16 and oral care each day with the help of caregivers in Japan.17,20. In Thailand, home-based tongue and mouth exercises are included as a means of potential improvements in various oral functions [19]. Dental care adaptations for dementia-sensitive practices were examined in Germany [18] and reflect the heterogeneity of interventions.

Comparator groups, in most RCTs, used standard practices or self-care [15, 16, 17, 20], ensuring that interventions were evaluated relative to real-world standards. Such interventions were methodologically robust; the quality of professional oversight was evident when studies employed teeth brushing with povidone iodine and professional care weekly, for instance, in Japan [21].

Table 3: Technical characteristics assessed

Outcome measures and Statistical Evaluations

The outcome measures differed but included oral as well as systemic health impacts. Such positive changes were also seen with respect to the Oral Health Assessment Tool (OHAT) in Taiwan [15] and Maximum Tongue Pressure (MTP) in Thailand [19], which achieved statistical significance with Wald χ² values in the first case and generalized estimating equation (GEE) analysis in the latter. Cognitive outcomes were also strong, showing significant changes over time in the scores of Mini-Mental State Examination (MMSE) for participants from China [16] and Japan [17]. In addition, intraoral disease prevalence in Germany [18] was shown to have statistically significant frequency differences (GLM: F(8, 776) = 103.40, p < 0.001).

Other significant results included increased sensitivity to cough reflex (OR = 5.3, 95% CI 1.7–16.0, p < 0.005) in Japan [20], and decreased pneumonia occurrence (p < 0.05) in institutionalized elderly individuals during receiving oral care [21]. Those results represented the complexity of positive benefits obtained from oral care intervention, including quality of life related to health and clinical results.

Figure 1: PRISMA study selection process representation

Quality assessment observations

Chen et al [15] demonstrated low bias risk in most studies being evaluated by using the RoB 2.0 tool (Figure 2); however, "some concerns" are noted only for domain D5, resulting in an overall low bias rating. Chen L, et al [16] had "some concerns" in all four domains, D2, D3, D4, D5, and thus got a final classifica on as "some concerns". Kikutani, et al [17] and Somsak, et al [19] also reported "some concerns" in various domains with low bias in only D4 and D3, respectively, and were classified as "some concerns". Watando, et al [20] had "some concerns" in all domains except for D5; they had a low bias in D5; the overall rating was low bias.

Figure 2: Assessment of bias using the RoB 2.0 tool

The studies evaluated using the AXIS tool (Figure 3)- Schaper et al [18] and Yoneyama et al [21]- presented different types of bias. Schaper et al [18] showed moderate risk for bias in the selection domain but low risk for all other domains thus resulting in an overall low risk assessment. In Yoneyama et al [21], the bias was low for most domains except attrition and reporting, which were rated as moderate, yet the overall bias remained low.

Figure 3: Assessment of bias using the AXIS tool

The results of the studies as a whole highlighted the various benefits conferred by oral medicine interventions in the management of dementia, although with different emphases and levels of impact. Chen et al [15] and Chen L et al [16] both demonstrated significant improvements in oral health outcomes, though the latter extended their findings to include modifications of microbiota and slowing of cognitive decline, thus suggesting a broader systemic impact. Similarly, Kikutani et al [17] supported the role of oral care in preventing cognitive decline, and this is aligned closely with Chen L et al [16], although the latter provided more comprehensive evidence linking microbiota changes to cognitive outcomes.

For example, Somsak et al [19] and Watando et al [20] shared the same angle of improvement in specific functions: oral motor function and cough reflex sensitivity, respectively. Both focused on functional benefits, although their outcomes were different in scope: Somsak et al [19] focused mainly on the strengthening and mobilizing effect of oral strength, while Watando et al [20] discussed a reduction in respiratory risks.

Yoneyama et al [21] differed from others in that it focused on the reduction of pneumonia and associated risks, which showed systemic benefits associated with oral care, thereby partially matching those of Watando et al. [20], who addressed systemic health but through different mechanisms. Schaper et al. [18] uniquely emphasized the adaptations for dental practice, which were necessary for dementia-sensitive care, as it places its focus on implementation more than direct health effects. Therefore, the findings confirm that oral medicine is essential for the management of dementia but differed in their focus as some highlighted systemic health (Chen L et al [16], Yoneyama et al [21], Watando et al [20]) while others focused on oral or cognitive improvements (Chen et al [15], Kikutani et al [17], Somsak et al [19]). The diversity in conclusions underlines different but complementary aspects of oral health interventions in dementia care.

The relationship between oral hygiene practices and the preservation of cognitive function is another field of ongoing research, whose underlying mechanisms are yet to be fully understood. However, the findings of some of these studies make sense if looked at as a totality. Orally, infections in animals have been reported to impair cognitive function by causing neuroinflammation and facilitating amyloid-β formation [22-23]. Conversely, attenuation of oral infection in these models has resulted in decreased neuroinflammation and amyloid-β burden, thus yielding better cognitive outcomes 32, 33. Furthermore, salivary microbiota linked with periodontitis has been identified to aggravate Alzheimer's disease pathology by modulating the gut-brain axis interactions in APPswe/PS1ΔE9 transgenic mice [24]. Specific probiotics, including Lactobacillus pentosus and Bifidobacterium bifidum, known to regulate periodontitis, have been explored to be beneficial in preventing cognitive impairments caused by Porphyromonas gingivalis by altering the gut microbiota in experimental models [25].

Tooth loss was also related with structural and functional brain changes, including decreased pyramidal cell density in memory-related areas of the brain in mice and decreased hippocampal volume in humans [26-27]. Experimental manipulations, such as giving dentures to rats, were found to reverse these effects, through enhancing the density of pyramidal cells and enhancing spatial learning as well as memory performance [28]. Additionally, alterations in mastication have been associated with the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which in turn has been related to the disruption of hippocampal neurogenesis and consequential cognitive deficit [39]. Restoration of masticatory function, however, diminishes HPA axis hyperactivity and consequential cognitive impairment [29]. Collectively, these reports from animal models suggest that a number of oral health interventions could play a role in preserving or enhancing cognitive function.

Many studies have not taken a holistic approach to assessment of oral health; this limits the ability to evaluate in a direct manner the effectiveness of oral health interventions and their association with changes in cognitive function [27-30]. Furthermore, it is unclear how much confounding factors such as depression and physical disability were controlled. Depression can lead to decreased motivation, thereby affecting an individual's adherence to oral health interventions [31], and physical disabilities can compromise the capacity to carry out everyday oral hygiene processes, thus influencing outcomes of interventions [32]. Some other factors, for example, polypharmacy and malnutrition, are especially relevant to people suffering from dementia. The use of five or more medications, known as polypharmacy, has been associated with adverse effects on nutrition through multiple mechanisms [33] and also significantly contributes to the development of dementia [34]. These confounders must be addressed in future studies to enhance the validity and generalizability of findings.

The MSME tool is also widely used to assess cognitive function, although its ability to detect subtle shifts in cognition raises concerns regarding its sensitivity for detecting intervention effects [35-36]. Future studies should consider measures of cognition that are more nuanced and comprehensive as well as the consideration of confounding variables with careful attention to the two to increase the validity of the conclusions.

Limitations

The findings included in the study had inherent limitations in which several had different study designs, intervention protocols, and outcome measures. This significantly hindered direct comparison and meta-analytic synthesis. The follow-up duration was also very heterogeneous and challenging as far as the assessment of long-term impacts is concerned. In some cases, the sample sizes were small, making generalizability limited. Most of the studies had no subgroup analyses to support further differential effects on demographic or clinical characteristics. Furthermore, the measurement tools of some of these studies were self-reported or caregiver-assisted, hence subject to bias; this was reflected in the outcome reporting as well.

Clinical recommendations

Based on the findings, oral care should be an integral part of dementia care with a focus on caregiver education and skilled supervision to establish consistency so effective care is ensured. There should be standardized intervention protocols to minimize variability and enhance comparability in studies to be done in the future. Long-term follow-up studies should be pursued to assess whether oral interventions have maintenance effects on the cognitive and systemic health outcomes. There is also a need to ensure that the dental professionals and healthcare providers in charge of the management of dementia should collaborate on an interdisciplinary level to tackle issues relating to complex interactions between oral and systemic health. Also, research into the future with innovative technologies and personalized interventions shall seek to enhance the effectiveness of oral care strategies for individuals with dementia.

The study had demonstrated an improvement in oral health outcomes and lessened the risks associated with systemic health in patients with dementia. Although some interventions helped to slow down cognitive decline, the critical findings emphasized the integration of oral care as a part of comprehensive management in dementia. The multifaceted benefits of oral health interventions were thus known, though strong evidence base and optimized implementation in clinical practice require further research.

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