Oral diagnostics: an integral component to geriatric health care

Abstract

Aging is inevitable, every day we live we age. The mouth is referred to as a mirror of overall health, reinforcing that oral health is an integral part of general health. Oral health reflects overall well being for the elderly population. Compromised oral health may be a risk factor for systemic diseases commonly occurring in age. Diagnosis and proper treatment is essential for healthy aging. Timely diagnosis, appropriate treatment and regular follow-up of both oral and systemic diseases are a prerequisite for active aging. Oral diagnostics is a revolutionary development with high potential to replace other investigative modalities. Changing demographics, including the increase in life expectancy and the growing numbers of elderly, has focused attention on the need for dental research activities to be expanded for geriatric dentistry. This paper is aimed to shed light on the growing elderly population and their ailments. It also aims to create awareness among health care providers about oral diagnostics and their application in geriatrics.

• Aging
• geriatric dentistry
• oral diagnostics

Introduction

Population projections for USA indicate that the elderly will constitute an increasing percentage of the population as we proceed into the twenty-first century. In 2001, the population of the United States was almost 278 million, and 12.6% of the population was 65 years of age or older [1]. By 2015, the population is expected to increase to 312 million, and 14.7% of the population will be aged 65 years or older. In 2030, which is within the practice lives of students currently enrolled in dental schools, the population will have increased to >350 million, and 20% of the population – one of every five members of the US society – will be 65 years of age or older [1]. With advances in oral health promotion and oral disease prevention in industrialized countries, more people retain their natural teeth into their old age as compared to a half century ago. The number of edentulous elderly (>60 years old) in USA has declined to 25% (versus 56% in 1957); and among the dentate elderly, they have an average number of 19 ± 0.2 teeth [2]. The National Survey of Oral Health in the US Employed Adults and Seniors: 1985–1986, conducted by the National Institute of Dental Research (NIDR), indicates that the proportion of edentulous seniors has decreased over the past 25 years, and the number of teeth at risk for periodontal disease and caries has increased [3].

Geriatric dentistry is the branch of dentistry that emphasizes dental care for the elderly population and focuses upon patients with chronic physiological, physical and/or psychological changes or morbid conditions/diseases. Ettinger and Beck developed a functional definition of the elderly based upon an older person’s physical ability to seek dental services. Aging population can be categorized into three broad functional groups [4]:

1. Functionally independent older,

2. Frail older adults and

3. Functionally dependent older adults

The significance of oral health

Oral care is important, like feeding and bathing, and must be promoted as an activity central to caring for older adults. The oral cavity has physiological as well as psychosocial significance. It is necessary for proper chewing, swallowing and digestion of food and is important for both verbal and non-verbal communication [5]. According to Kay and Locker, the accepted definition of oral health is: “a standard of health of the oral and related tissues which enables an individual to speak and socialize without active disease, discomfort or embarrassment and which contributes to general well-being”. A combination of factors contribute to the maintenance of oral health including adequate nutritional and fluid intake, the ability to masticate food properly, adequate saliva production and effective oral hygiene [6]. The US Surgeon General’s report, Oral Health in America, emphasizes the fact that oral health is integral to general health and describes the disparities in the availability of dental care, especially for very young and very old populations. The report uses the phrase “silent epidemic” to characterize the disparity between the epidemic of oral disease and the silence from those who need care. This report highlights many reasons that dental care is of particular importance for frail older adults [7].

Oral care neglect occurs at significant levels in long-term care settings. One of the earliest investigations, which analyzed 442 institutionalized elderly in Edinburgh, Scotland, revealed that 65% of the sample wearing dentures had visible soft debris, calculus and stains that would not wash off; 53% had denture-induced pathology requiring treatment about which staff were unaware [8]. Similar findings of poor oral hygiene in nursing home samples were found in the US studies as well. Poor oral hygiene, broken/loose dentures, dry mouth, bleeding gums and periodontal disease are commonly reported [9].

Oral-systemic linkage

The oral cavity is a portal of entry for microbial infections. Recent correlation studies have raised concerns about the possible linkage between oral infection/chronic inflammation and systemic disease development/progression [11]. Saliva, the most available and non-invasive biofluid of the human body, permanently “bathes” the oral cavity and is trying to cope with an ever-changing milieu. Saliva includes a large number of inorganic and organic compounds, which act as a “mirror of the body’s health” [10]. The realization that the oral cavity influences and is influenced by, events occurring in the rest of the body has generated a great deal of interest in “oral-systemic links”. The oral-systemic diseases linkage is a special health concern for the elderly since effective oral hygiene is usually compromised in patients with physical and neurological changes. Accordingly, elimination of the oral flora burden should be emphasized for geriatric patient care [11]. Recent reports have been made of associations among severe periodontal diseases, oral hygiene and coronary heart disease [12]. Cancer, the second leading cause of death among the elderly, also has a significant impact on the oral cavity. Oral and pharyngeal cancers account for ∼5% of all cancers, and they increase in prevalence with age. Cancer treatments including chemotherapy, radiation and surgery can cause severe stomatitis (inflammation of the mouth), xerostomia (dry mouth), disfigurement, altered speech and mastication, loss of appetite and increased susceptibility to oral infections – including those that cause caries and periodontal diseases [13].

Effect of aging on oral tissues

Older adults suffer from the cumulative effects of oral diseases over their lifetime. This results in extensive oral disease [14]. Data on the effect of aging on oral tissues are scarce. Studies indicate that the prevalence of root-surface caries increases with age, and there is an association between root caries and gingival recession. The 1985–1986 NIDR Survey indicated that root-surface lesions were present in 67% of the males and 61% of the females in a senior population [15].

Atrophy and loss of the oral mucosa also occurs slowly and alveolar bone resorption eventually leads to loss of the height of the alveolar structure and may result in tooth loss. Due to medications there is reduced salivary flow that impairs debris removal and increases the risk of tissue ulceration and accumulation of dental caries [16].

Oral cancer, is mostly a disease of older adults. According to the American Cancer Society, ∼30 000 people in USA develop oral cancer each year, and only about half of these individuals will survive 5 years after diagnosis. Oral cancers can lead to disfigurement and the need for prosthetic appliances to restore function or esthetics [15].

Several studies suggested that 68–95% of persons 65 years or older take medication. The average number of drugs (prescription and/or non-prescription) used by this group is 1.4–4.3. With physiological aging and multiple pathologies, elderly patients are more susceptible to drug interactions and adverse effects [17,18]. A large number of medications are capable of inducing dry mouth (xerostomia) and salivary gland hypofunction which impact upon oral health [15].

Oral diagnostics

For the past two decades, oral health researchers have been developing salivary diagnostic tools to monitor oral diseases (including periodontal diseases) as well as for caries risk assessment [19].

Although blood is still the gold standard for diagnostics of diseases and drugs, oral diagnostics has the same and may be an even larger diagnostic potential. Principally, all substances that are present in blood may be monitored in saliva, since serum components leak from the gingival crevice into the oral cavity. The concentration of serum components in saliva may be enhanced by normal actions like tooth brushing which results in a fourfold increase of serum albumin [20].

Oral-based diagnostics has evolved to include a range of approaches from merely visual inspection of the oral cavity to collecting a fluid or tissue sample and analyzing it using modern micro- or nano-based technologies. In 2002, NIDCR initiated a research effort in the area of salivary diagnostics and progress is being made toward developing technologically viable systems that are suitable for commercialization [21]. The collection of oral samples is non-invasive, does not require a trained phlebotomist and special facilities and is ideal for vulnerable populations including pediatric, geriatric and hemophiliacs [22].

Whole saliva (mixed saliva or oral fluid) is a mixture of oral fluids and includes secretions from both the major and minor salivary glands. In addition to several constituents of non-salivary origin, such as gingival crevicular fluid GSF, the area between tooth and marginal free gingiva, oro-naso-pharyngeal secretions, serum and blood derivatives from oral wounds, bacteria and their metabolites, viruses and fungi, desquamated epithelial cells, electrolytes, leukocytes, other cellular components and food debris [23,46]. Oral fluid is a perfect medium to be explored for health and disease surveillance. In addition, for special populations including geriatric and field studies in geographically remote areas, blood draws can be complicated when compared to the collection of an oral sample [24].

Applications of oral diagnostics

Dental caries

The incidence and prevalence of dental caries are increasing in older adults [25]. In the last few decades, there has been a focus on the utilization of saliva for bacteriological tests that give an indication of dental caries risk [26]. Saliva secretion rate, buffering capacity and counts of mutans streptococci and lactobacilli, have proven to be sensitive parameters in caries prediction models. Diagnostic kits for S. mutans and Lactobacillus spp. counting are widely used in dental practice and can be conducted without laboratory facilities. They are based on traditional culturing techniques in selective media but analysis by PCR is also possible.

Commercial kits are available for determination of salivary buffering capacity [27]. Saliva buffering capacity can be assessed immediately after the collection using a commercial Dentobuff strip test [28].

Periodontal diseases

Periodontitis is a leading cause of tooth loss in adults, affecting >50% of the US population. Localized nature and proximity of periodontal lesions within the oral cavity, saliva is a natural biological fluid for measurement of microbial and protein biomarkers of the disease process [29]. Intracellular enzymes are increasingly released from the damaged cells of periodontal tissues into the gingival crevicular fluid and saliva, as well as in the surrounding fluids. Those particularly relevant in this group of enzymes are the following: aspartate and alanine aminotransferases (AST and ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase, creatine kinase, alkaline phosphatase, acidic phosphatase. LDH and AST can help monitor the progression of the periodontal disease. These enzymes appear to be useful to test the activity of periodontal disease or to measure the effectiveness of periodontal therapy [30]. Though efficient, such clinical methods do not provide adequate information for identifying people at risk, disease activity, causative agents and treatment outcome. This information could be provided by oral-based diagnostics. DNA can easily be isolated from oral epithelial cells, collected by use of a buccal swab, one of the most common oral diagnostics. There is a large, genetically determined, variation in susceptibility for periodontal disease. Mutations in the cathepsin C gene have been identified as causal for the Papillon–Lefèvre syndrome, including severe forms of prepubertal periodontitis [31].

Taste disorders

Saliva is necessary for taste, although its function in terms of taste has not yet been fully elucidated. It is established that loss of one of these salivary proteins, gustin or carbonic anhydrase VI, a zinc containing glycoprotein, was responsible for loss of taste and smell in some of the patients. Some studies have already reported that carbonic anhydrase VI (a zinc metalloprotein) is decreased in patients with taste disorders [32].

Oral cancer

Using saliva, a biofluid that is readily accessible via a totally non-invasive method, has long been recognized as an aid in detection of cancer. This is an ideal opportunity to optimize state-of-the-art saliva-based biosensors for salivary biomarkers that discriminate between diseases [21]. Mutation of the tumor suppressor gene p53, a tumor suppressor gene is common in many malignancies. Elevated levels of salivary defencine-1 were found to be indicative of the presence of oral squamous cell carcinoma [33]. Salivary transcriptome diagnostics can be a suitable tool for the development of non-invasive diagnostic, prognostic and follow-up tests for cancer. Distinct mRNA expression patterns can be identified in saliva from cancer patients, and the differentially expressed transcripts can serve as biomarkers for cancer detection. The rationale is that oral cancer cells are immersed in the salivary milieu and genetic heterogeneity has been detected in saliva from patients with OSCC [34,35]. Molecular markers for the diagnosis of OSCC can be quested in 3 levels: (1) changes in the cellular DNA, which result in (2) altered mRNA transcripts, leading to (3) altered protein levels (intracellularly, on the cell surface or extracellularly) [36]. Allelic loss on chromosomes 9p has been observed in OSCC. Mitochondrial DNA mutations have also been useful targets to detect exfoliated OSCC cells in saliva [37]. The level of carcinoembryonic antigen in saliva in the presence of malignancies of the oral cavity is increased, while the level of gastrointestinal cancer antigen is decreased [38].

Infectious diseases

A variety of infections has also been monitored by the detection of specific antibodies in saliva [23]. PCR technology has been proved to be highly sensitive and specific for detecting of H. pylori DNA in the mouth using biological markers found in saliva [39]. Saliva was also found to be a reliable alternative to serum for identification of the antibody of parvovirus B19 [40].

Another infectious disease of the oral cavity that can be diagnosed by saliva is candidiasis through the presence of Candida species in saliva. The presence of antibodies to other infectious organism such as Borrelia burdogferi can also be detected through the saliva [41]. Detection of the human immunodeficiency virus (HIV) is a very good example of using saliva to diagnose infectious disease. When detecting HIV using the ELISA method in combination with the Western blot test, saliva is, compared to blood and urine has greater advantage owing to its higher specificity and sensitivity [42]. Also for diagnosing autoimmune diseases like Sjogren’s Syndrome. Sialochemistry may also be used to assist in the diagnosis of SS. A consistent finding is increased concentrations of sodium and chloride. This increase is evident in both whole and gland-specific saliva. In addition, elevated levels of IgA, IgG, lactoferrin and albumin, and a decreased concentration of phosphate were reported in saliva of patients with SS [43].

Drug monitoring

Diagnostic testing of drugs and prescription medicines using saliva/oral fluid is now widespread and replacing the previously used urine. The unbound fraction of a drug is usually the pharmacologically active fraction. This may represent an advantage of drug monitoring in saliva in comparison with drug monitoring in serum, where both bound and unbound fractions of a drug can be detected [44].

Cardiovascular diseases

Cardiovascular diseases are a leading cause of death all over the world. Enzymes found in saliva, such as amylase, have been used for post-operative control of patients who had cardiovascular surgery. Chatteron et al. found the direct relationship between raised levels of alpha amylase and heart rate which increases under stress [45]. Acute myocardial infarction (AMI) triggers an inflammatory reaction, which plays an important role in myocardial injury. Inflammatory markers such as C-reactive protein (CRP) reflect the extent of myocardial necrosis and correlate with cardiac outcomes following AMI. Salivary levels of CRP are significantly higher in patients who have suffered an AMI and correlate positively with serum concentrations [46].

Role of nano bio chips using saliva as a diagnostic tool

Currently, biologists, engineers and dental practitioners are developing “lab-on-a-chip” platforms that use oral fluids in rapid tests to accelerate clinical decision making [47]. Recently investigated the feasibility and utility of saliva as an alternative or complement to serum diagnostic fluid for identifying biomarkers of AMI [48]. For saliva, the top 10 biomarkers that yielded the most valuable information for diagnosis of AMI from a single salivary biomarker perspective included CRP, soluble intercellular adhesion molecule 1, soluble CD40 ligand, myeloperoxidase, matrix metalloproteinase-9, tumor necrosis factor-alpha, myoglobin, interleukin-1 beta, adiponectin and RANTES [46].

Coelic disease

Celiac disease is a congenital disorder of the small intestine that involves malabsorption of gluten. To diagnose Celiac disease, detection of IgA and antigliadin antibody in saliva shows high specificity and low sensitivity whereas their determination in serum is highly sensitive and less specific. Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for coeliac disease [49].

Diabetes

Insulin is able to stimulate salivation so in diabetes mellitus patients the salivary flow rate decreases. In diabetic patient albumin and IgG concentrations of non-stimulated saliva are lower than healthy individuals. Patients with diabetes mellitus express higher levels of amylase and secretory IgA in whole saliva constituents [50].

Alcoholic liver cirrhosis

Parotid enlarges in 50% of the patients with alcoholic liver cirrhosis, which results a 50% reduction of the salivary flow rate and a reduction of salivary sodium, bicarbonate and chlorine concentrations. The total salivary protein concentration decreases as well [51].

Future prospects

In many cases, oral-based tests have demonstrated its efficacy. oral-based diagnostics has made it possible to detect diseases and monitor other conditions at the point of testing. But, approved commercial tests are unavailable. For example, monitoring of steroid levels; association of CRP with periodontal disease. Many treatment modalities for geriatric patients are still experimental. In situations like assessment of prostate specific antigen, malnutrition, markers for arteriosclerosis, Alzeimer’s and Parkinson’s disease oral-based test could be useful. But studies are yet underway.

Conclusion

Oral diagnostics is a revolutionary development with high potential to replace other investigative modalities. The convergence of microfluidics and oral-based diagnostics has made it possible to detect diseases and monitor other conditions at the point of testing. The current development of diagnostic biomarkers (via proteomic and genomic approaches) in conjunction with technological developments in salivary diagnostics will lead to the development of robust diagnostic tools for dentists to use in making clinical decisions and predicting treatment outcomes.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.