Low-dose X-ray imaging may increase the risk of neurodegenerative diseases 低劑量 X 射線成像可能會增加阿爾茨海默氏症、帕金森病等的風險。

Editor’s note: Low dose does not mean risk free.  Dentists often argue that exposure to dental x-ray is even smaller than daily exposure to environmental background ionizing radiation.  Not true. First, any exposure means some risk! so if we can reduce we should take measures to reduce the exposure, and second, dental like other medical x-ray is much dense and sharp delivered in a split second, and the damage is not comparible to that induced by envinronmental ionizing radiation.  Good news is, x-ray machine manufacturers keep improving the x-ray imaging technologu to minimize the exposure.  Bad thing is, many dentists would not like to update thier machine so fast, and patients have to expose themselves to unneccessary higher dose of x-ray exposure.

編者按:低劑量並不意味著沒有風險。 牙醫經常爭辯說,暴露於牙科 X 射線甚至比每天暴露於環境背景電離輻射還要小。 不對。 首先,任何接觸都意味著一定的風險! 所以如果能減少就應該採取措施減少照射,其次,牙科和其他醫學X線一樣,都是一瞬間發出的密集而銳利的射線,其傷害是環境電離輻射所無法比擬的。 好消息是,X 光機製造商不斷改進 X 光成像技術,以盡量減少曝光。 不好的是,許多牙醫不希望更新他們的機器這麼快,患者不得不讓自己暴露在不必要的更高劑量的 X 射線照射下。

Medical Hypotheses

Volume 142, September 2020, 109726

Low-dose X-ray imaging may increase the risk of neurodegenerative diseases

Under a Creative Commons license
open access

Abstract

The hypothesis presented here explores the possibility that X-ray imaging commonly used in dental practices may be a shared risk factor for sporadic dementias and motor-neuron diseases. As the evidence will suggest, the brain is ill-equipped to manage the intrusion of low-dose ionizing radiation (IR) beyond that which is naturally occurring. When the brain’s antioxidant defenses are overwhelmed by IR, it produces an abundance of reactive oxygen species (ROS) that can lead to oxidative stress, mitochondrial dysfunction, loss of synaptic plasticity, altered neuronal structure and microvascular impairment that have been identified as early signs of neurodegeneration in Alzheimer’s disease, Parkinson’s, amyotrophic lateral sclerosis, vascular dementia and other diseases that progressively damage the brain and central nervous system. Although genes play a role in all outcomes, the focus here will be on the non-genetic processes at work. Common assumptions regarding the risks of low-dose IR will be addressed, such as: 1) comparing rapid, repeated bursts of man-made IR sent exclusively into the head to equivalent amounts of head-to-toe background IR over longer periods of time; 2) whether epidemiological studies that dismiss concerns regarding low-dose IR due to lack of evidence it causes cancer, heritable mutations or shortened life spans also apply to neurodegeneration; and 3) why even radiation-resistant neurons can be severely impacted by IR exposure, due to IR-induced injury to the processes they need to function. Also considered will be the difficulty of distinguishing the effects of dental X-ray exposure from similarly low amounts of background IR and where to find the evidence that they may, in fact, be responsible for neurodegeneration. Finally, the long-standing belief that whatever risks are inherent in dental radiography must be undertaken for the sake of oral health is challenged on two counts: 1) while dentists continue to drape their patients in lead-lined aprons, the most effective IR safety precautions are often ignored; and 2) there is an alternative dental imaging technology that does not use IR. While the thrust of this article will be on dental radiation and will touch on how age, gender, X-ray equipment and protocols may increase risk, chiropractic radiographs also will be considered because they focus exclusively on the central nervous system. If X-ray imaging is found to be associated with neurodegeneration, the risk-versus-benefit must be reevaluated, every means of reducing exposure implemented and imaging protocols revised.

Introduction

Little is known about the causes of neurodegenerative diseases, whether they progressively attack the mind and cause dementia or, in the case of motor-neuron diseases, devastate the body. When an individual with a neurodegenerative disease has inherited gene mutations associated with that diagnosis it is termed “familial,” while all other cases – which comprise the vast majority [1] — are considered “sporadic.” A world-wide search for disease-modifying risk factors for dementia has not yielded much beyond recommending the management of cardiovascular risk factors and regular exercise [2]. Once a neurodegenerative disease has been diagnosed, there is little in the way of treatments that can stop, reverse or even slow disease progression.

The hypothesis presented here explores the possibility that diagnostic X-ray imaging commonly used in dental practices may be a shared risk factor in the cause of neurodegenerative diseases. As the evidence will suggest, the brain is ill-equipped to manage the intrusion of low-dose ionizing radiation (IR) beyond that which is naturally occurring. When the brain’s antioxidant defenses are overwhelmed by IR, it produces an abundance of reactive oxygen species (ROS) that can lead to oxidative stress, mitochondrial dysfunction, loss of synaptic plasticity, changes in neuronal structure and microvascular disturbances [3], [4], [5], [6], [7], [8], all of which have been identified as early signs of neurodegeneration in Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), vascular dementia and other diseases that progressively damage the brain and central nervous system. Although genes undoubtedly play a role in all outcomes, the focus here will be on the non-genetic processes at work, especially now that low-dose IR, widely considered harmless, is a frequent component of dental practices for a majority of the population.

The possible risks of dental X-rays have been repeatedly dismissed due to several assumptions that deserve reevaluation, such as: 1) doses used in dental radiography can be confidently compared to those of apparently harmless background IR; 2) the only serious biological effects of IR are cancer, heritable mutations and shortened life spans; 3) the amount of IR used for diagnostic imaging is so low as to be difficult if not impossible to distinguish from the effects of naturally occurring IR; 4) the brain is resistant to the effects of IR because mature neurons no longer actively divide, when they would be subject to IR-induced DNA damage, and; 5) even if there are risks inherent in dental IR, oral health is so important that any theoretical risks are outweighed by the known benefits of obtaining diagnostic information. Addressing these points, briefly:

1)

When comparing the risks of dental IR to background radiation, rapid, repeated bursts of man-made X-rays sent exclusively into the head cannot be compared to an equal amount of head-to-toe background IR, when only a small portion of naturally occurring IR could be expected to have head involvement. Further, clustered exposures to man-made radiation have the potential to overwhelm natural repair mechanisms [9].

2)

The majority of studies regarding radiation’s biological effects have cancer, heritable mutations or shortened life spans as endpoints. Because doses lower than 100 millisierverts (mSv) are not associated with these specific adverse effects [10], low-dose IR has not been considered a cause for concern. However, neurodegeneration, which may have a longer latency than cancer, has not been sufficiently studied as an endpoint.

3)

It is true that dental IR doses are so low as to make it difficult to distinguish their effects from those of background radiation. A recent review of the biological effects of dental X-ray exposure expertly found fault with virtually every such effort undertaken since 1970 on the basis of study size, lack of precise data or failure to account for possible confounders, etc. [11]. Yet while these apparently flawed studies were being conducted, a huge field experiment spanning more than a century was taking place and the results, which continue to accrue, are undeniable: Humans, who alone among primates are subjected to frequent, life-long dental X-rays, also are the only primate to suffer neurodegeneration, despite being equipped with nearly identical genes and cellular mechanisms [12]. As our closest non-human primate cousins age, their brains develop some of the same pathology implicated in Alzheimer’s, such as misfolded abeta protein accumulations, and they may exhibit some cognitive decline, but they do not develop dementia [12]. This suggests that primates have evolved equipped to repair neurological damage incurred by background IR — but not necessarily the additional burden of man-made exposures.

4)

Because mature neurons undergo a very low level of cell division, they have been thought to be robustly resistant to radiation effects — yet neurons do not exist in a vacuum. Neurons and the synapses that transmit information have high energy needs that cannot be met when there is mitochondrial dysfunction [6], [13] one of the consequences of IR exposure [3].

5)

Oral health certainly is important to overall health, but while dental imaging technology is constantly changing and, in some cases, reducing IR exposure [14], [15], at least one widely recognized safety measure that could greatly reduce patient exposure has been ignored by virtually all dentists: utilizing rectangular collimators on their X-ray machines [14]. Further, within the last two decades, an alternative form of dental imaging that does not use IR has become available [16], [17].

In presenting the case for this hypothesis, symptom and pathological commonalities across diseases will be discussed, as well as many known effects of low-dose IR as they might apply to neurodegeneration. Sources of background and man-made radiation, as well as the average per capita exposure, have been covered thoroughly elsewhere [18]. Instead, the focus here will be on dental radiation and will touch on how age, gender, dental imaging equipment and protocols may increase risk unnecessarily. Chiropractic radiographs also will be considered, because unlike other common uses of diagnostic imaging, they focus exclusively on the central nervous system and some data suggest that on a lifetime basis may expose up to half the U.S. population.

Symptom & pathological commonalities across diseases

While neurodegenerative diseases vary widely in many respects, there are also remarkable commonalities across diseases that suggest they may have a shared etiology. For example, depression often precedes diagnosis in AD [19], [20], PD [21] and ALS [22] by one or more years. Executive dysfunction is found in people with AD [23], PD [24] and ALS [25]. The development of depression, anxiety and apathy has been observed in people with AD, PD and ALS [26], [27], [28], [29], as has the loss of olfaction [30], [31], [32] and gait changes [33], [34].

Perhaps the most compelling evidence suggesting a common etiology is the prevalence of mixed brain pathologies. While scientists have identified “signature” pathologies used to diagnose neurodegenerative diseases, such as amyloid plaques in AD, alpha-synuclein inclusions in PD, and TDP-43 in ALS, it has become clear that these pathologies are not mutually exclusive [35]. For instance, as different as AD and PD are for those living with the diseases, on autopsy the majority of brains with AD pathology also had Lewy-related pathology with alpha-synuclein more typical of PD [36]. A consortium of European researchers found mixed pathologies in slightly more than half of the cases analyzed in dementia brain banks [37]. This prevalence of overlapping pathologies begs the question: Could these various protein irregularities, although they are different in nature and may occur in different brain regions, have the same etiology?

Effects of low-dose IR on the brain

While the most widely known harmful risk of high-dose IR is cancer, low-dose IR quietly sets into motion a cascade of lesser-known effects that can be especially detrimental when they occur in the brain, such as: 1) increased ROS levels leading to oxidative stress; 2) mitochondrial dysfunction; 3) loss of synaptic plasticity; 4) altered neuronal structure and 5) impaired microvasculature, which individually and in combination can contribute to neurodegenerative disease.

Elevated ROS levels and oxidative stress

IR is one of many environmental insults such as air pollution, industrial solvents, and certain chemicals that can cause elevated levels of (ROS) [38]. In the natural course of events, ROS, which have essential and beneficial effects at low and moderate levels, are quickly resolved by any one of a number of antioxidants [38]. However, neurons have weak antioxidant defenses so when ROS levels are too high to achieve homeostasis, the resultant oxidative stress has damaging effects that can even cause neuronal death [39], [40]. Oxidative stress also causes mitochondrial dysfunction, which deprives neurons of the energy they need to function [3], [39], [40] and loss of synaptic plasticity, affecting the brain’s ability to process, store and retrieve information [7]. Other prominent consequences of oxidative stress are protein denaturing, misfolding and aggregation through various means, such as the generation of free radicals that attack proteins or the disruption of the processes by which misfolded proteins are repaired [3], [41], all of which are characteristic of neurodegeneration.

Oxidative stress has been implicated in AD, PD, ALS and Huntington’s disease (HD), due in part to the way it compromises cell membrane integrity, induces an inflammatory response and fails to meet high neuronal oxygen needs [4], [42]. Dopaminergic neurons in the substantia nigra, the loss of which is key to PD progression, are especially susceptible to the effects of oxidative stress [4], [6], [39].

Mitochondrial dysfunction

Mitochondria are essential organelles with a number of functions, one of the most important of which is producing energy in the form of adenosine triphosphate (ATP) [5]. Neurons, which require a great deal of energy to function, are at risk if their energy demands are not met [5]. Among neurodegenerative diseases that have been associated with impaired mitochondria are AD, PD, ALS, HD and multiple sclerosis (MS) [5], [43]. A review of the biological effects of low-dose IR found evidence suggesting IR could cause irreversible changes in mitochondria that could lead to persistent ROS production [3]. When mitochondria produce too much ROS, their membrane integrity can become compromised, setting off a set of chain reactions that can result in cell death [44]. The damaging effects of IR can also cause ROS in non-irradiated cells [3]. The mechanism of this phenomenon, termed the “bystander effect,” is not well understood but is thought to involve chemical signaling and/or scatter radiation [3], [45].

Loss of synaptic plasticity

The brain requires a disproportionately large amount of energy to function, with most of that energy expended on synaptic transmissions [6], [46]. The ability to process thoughts and form memories depends upon networks of neuronal synapses that maintain this constant flow of information, actively undergoing morphological changes as necessary [46]. Oxidative stress causes a loss of this synaptic plasticity, which is a factor in many neurodegenerative diseases such as AD, PD, ALS and HD [13], [46]. There is evidence that synaptic dysfunction is responsible for early cognitive deficits found in neurodegenerative diseases prior to neuronal death [46]. IR has been shown to disrupt neuronal signaling pathways in mice in such a way that could explain cognitive deficits similar to those seen in advanced aging and AD [47].

Alterations in neuronal structure

Animal studies showed that even small amounts of scatter IR can alter neuronal structure, reducing the length, density and complexity of dendrites [45], which are neuronal projections necessary for synaptic contact [7]. A decrease in dendritic density can precede neuronal death [46].

Microvascular changes

Vascular dementia accounts for up to 20 percent of dementias and frequently co-occurs with AD and other neurodegenerative diseases [48], [49], [50] Although there are many known risk factors for vascular dementia [8], [49], head exposure to IR is of interest here because it can lead to microvascular disturbances, endothelial dysfunction and reduced capillary density [7], [8], although more study is indicated for doses under 0.5 Gy [51]. Animal studies suggest that some of the gait changes observed in people with neurodegeneration may be related to vascular impairment. One rodent study found that exposure to low-dose IR caused impairments in skilled walking [52]. A separate study that attributed IR-related gait abnormalities in mice to microvascular damage noted that neurovascular cells, such as the astrocytes and endothelial cells that are critical to the blood–brain barrier, are radiosensitive [53]. A review of IR’s immune and inflammatory effects on the brain found that “even doses in the range used for diagnostic purposes might have long-lasting consequences and might contribute to the development of radiation-induced late cognitive impairment [8].”

IR and multiple sclerosis

Like other neurodegenerative diseases, the cause of MS is unknown, although it is distinct from others discussed here because it is considered an autoimmune disease. IR’s possible role in causing multiple sclerosis, an unpredictable disease with different neurological manifestations, has been thoroughly if inconclusively reviewed elsewhere [41]. The review noted evidence that workers in the radiology field, people living in geographical areas with a higher concentration of cosmic radiation or individuals with a history of X-ray imaging were found to have a higher risk of MS [41], [54].

Key characteristics of MS, such as inflammation, axonal damage and demylenation, can result when oxidative stress causes disruptions in the immune system and blood–brain barrier [41], [55]. Interestingly, unlike many neurodegenerative diseases that have demonstrated a lower incidence of cancer [56], [57], [58], [59], a prospective population-based study of people with MS found a striking 52 percent higher risk of CNS cancer, compared to population controls [60]. The National Council on Radiation Protection and Measurements, in a report on ionizing radiation’s effect on the CNS, found the “mechanisms leading to CNS damage are likely independent of the mechanisms leading to cancer, even though the initiating events may be the same. However, it is possible that some mechanisms are involved in both cancer induction and CNS impairment, for example immune activation and dysregulation” [61]. Immune dysregulation could explain why some viruses have been associated with MS, possibly indicating they are a consequence of IR rather than a cause of MS.

A lifetime of dental X-rays, starting at a young age

In 2017, 85 percent of children aged 2 through 17 visited a dentist, according to the National Center for Health Statistics. The Food and Drug Administration (FDA) and American Dental Association (ADA) periodically issue joint guidelines for the selection of patients for dental X-rays. In accordance with the latest recommendations, last revised in 2012 and updated as of June 2019, a child as young as two years old may receive two or more X-rays at his or her first appointment. That child will be recalled for two or more X-rays every six to 24 months, depending upon whether he or she has shown any evidence of tooth decay. When permanent teeth erupt, that child will likely have a panoramic X-ray in addition to the bitewings and selected periapical (view of the tooth crown to the tip of its root) images that are repeated every 6 to 36 months, depending upon dental history. In adolescence, if there is evidence of generalized oral disease or a history of caries, a full mouth series is recommended. Adults who visit the dentist — as two thirds of those 18 and older did in 2017 — can expect X-rays every 6 to 36 months, depending on their dental history, for the rest of their lives, as long as they have teeth.

The many variables involved in estimating dental IR doses

Efforts to reduce diagnostic IR exposure that began about a decade ago have been largely successful, with a 15 to 20 percent decrease in the effective population dose of diagnostic imaging reported in 2019 [18], but no such reduction was achieved dentistry. In fact, due to recalculations involving tissue weighting — the method by which different tissue, such as the thyroid gland or brain, are identified as being more sensitive to IR — the updated effective dental intraoral dose is five-fold higher than the estimate published in 2009 [18], [62]. This recalculated effective population dose only applies to intraoral radiography and does not reflect additional radiation received from panoramic or CBCT radiography, each or which deliver much higher radiation doses than intraoral [14], [18], [63].

It is challenging to determine how much IR a dental patient receives as there are many variables. About 85 percent of dental practices have switched to using digital intraoral X-ray technology [14], which can result in a significant exposure reduction. Digital panoramic X-rays also reduce the radiation dose over film-based systems, although to a lesser degree due to anatomical areas that are continuously exposed as the equipment rotates around the patient’s head [63]. However, while these reductions in dose were being achieved, the use of cone-beam computer tomography (CBCT) — which takes multiple images to create a 3D view — has made steady inroads into general dental practices [14].

To provide an idea of how wildly dosages may vary, a full mouth series of 18 intraoral images with digital receptors or E- and F-speed film and rectangular collimation is considered equal to 4.3 days of background radiation [15]. However, in the United States, where virtually all dentists use circular collimation [14], a full-mouth series would be equivalent to 21 days of background IR [15]. The same series taken with the slower D film speed favored by dentists who do not use digital equipment was calculated to be equal to 47 days of background radiation [15]. Panoramic X-rays, which vary tremendously among brands and models, can deliver doses from one to five times higher than a full mouth series [63].

Perhaps because comparisons to background radiation are intended to be reassuring, there are no such estimates available for CBCT radiography. Another way to measure differences in radiation is the unit Sievert (Sv). A single intraoral tooth X-ray delivers an average dose of 0.8 μSv [63]. To provide an example of how much more IR is involved in CBCT radiology, a study comparing different CBCT brands and models with large field of view found adult exposure ranged from 43 to 1073 μSv, while child exposure with medium- to-large-field of view was between 13 and 769 μSv [64]. An industry survey estimated that in 2014–15, more than 5 million CBCT dental exams occurred in the United States, of which nearly 1.5 million were of children and adolescents [14].

Widespread lack of patient radiation protection

Meanwhile, while dentists continue to drape their patients in lead-lined aprons, there have been serious lapses in protecting them from unnecessary IR exposure. Possibly the most important means of dental radiation reduction – the shape of the collimator, which is the X-ray tube aimed at the patient’s head – has been ignored [14]. Rectangular collimators reduce patient IR exposure from 60 to 80 percent compared to circular collimators [15], [65], yet 99.4 percent of dentists surveyed in 2014–15 continue to use circular collimation [14]. And while 85 percent of dentists have switched to digital X-ray equipment, most of the remaining dentists still use the slowest film that doubles the required exposure time [14], despite long-standing recommendations to use faster film from the ADA, National Radiation Council on Protection and Measurements and the American Academy of Oral and Maxillofacial Radiology. An industry survey accurately reports that the majority of dentists use different radiation settings for children and adults, but there is little excuse for the 30 percent who do not [14].

Extra X-rays linked to retakes and payment practices

There are many reasons dentists undertake radiography — indeed, the FDA-ADA guidelines provide 29 potential justifications and allows that there might be more. Digital equipment has made the ease of retaking X-rays such that it threatens to erode some of the benefits of dose-reduction [66]. There is also the temptation to retake X-rays when part of the image is missing due to film placement errors or rectangular collimation, even though there may be sufficient information available for diagnostic purposes [65]. However, clinical considerations are not the only determinant of how many radiographs are taken. A Scottish study that analyzed more than one million treatment claims over 10 years found that dentists took substantially more radiographs in two circumstances: when they were paid on a fee-for-service basis and/or when the images were cost-free to patients [67] — circumstances that are often the same in this country due to the way insurance coverage is structured. When the risk to patients is considered so low as to be inconsequential, this conscious or unconscious bias towards extra imaging would not seem to be important. However, recommendations are based on the calculated statistical risk for cancer, heritable mutations and shortened life span, not neurodegeneration [14].

Alternative imaging technology that does not use IR

An exciting development in dental technology that has gone almost unnoticed is an imaging technology that can detect dental decay and tooth fractures even better than X-rays [16], [17]. The technology uses near-infrared light that makes teeth transparent, trans-illuminating fissures and early caries with a higher degree of detection than traditional radiography [16], [17]. Dentists use different radiography equipment and techniques to assess different aspects of oral health, so while this non-ionizing technology would not entirely replace X-ray machines, it could be used where possible to reduce patient IR exposure.

Chiropractic X-rays: focused on the central nervous system

As alternative medicines have gained ground among the public, so has the use of spinal manipulation. According to a National Health Statistics survey, in 2012 8.4 percent of American adults and 3.3 percent of children aged 4–17 visited chiropractors or osteopaths for manipulations. Evidently, most people are satisfied that chiropractors helped them: A 2015 Gallup poll reported that about two thirds of those who had visited a chiropractor said it was effective for neck and back pain. The same poll determined that about half of Americans have visited a chiropractor at some point in their lives.

Chiropractors are trained in radiography and about half of those practicing own their own X-ray equipment [18]. It is common for chiropractors to require one or more spinal X-rays to diagnose new patients, with some chiropractors taking additional radiographs at intervals to track progress. The most recent estimated number of chiropractic spinal X-rays is 4.5 million a year [18]. Without questioning the benefits of spinal adjustments, is this IR exposure of value? A review of current chiropractic practices found that by a variety of different measures such as the effect on treatment, over diagnoses, legal considerations and cost, “the potential benefit from spinal X-rays does not outweigh potential harms [68].”

At-risk populations: women & children

Not all IR exposure is equal, even when the doses are the same. How a patient responds to IR depends on genetic predisposition, age, gender, tissue type and bodyweight. Even different types of neurons have different sensitivities to oxidative stress [39].

Women are dramatically more radiosensitive than men, with the estimated risk of cancer 52 percent greater [10]. Many of these cancers are gender and tissue specific, such as thyroid, breast and ovarian cancer and can be successfully treated, but even so, women’s risk of a cancer death is 37.5 percent higher than that of men [10]. Does this radiosensitivity make women more vulnerable to non-cancerous effects at much lower doses? A rodent study found that low-dose IR scatter radiation caused marked deficits in the prefrontal cortex — which is the seat of executive function — in female but not male subjects [45]. Reduced volume in the prefrontal cortex has been associated with depression [69], which is substantially more prevalent in women than men.

Of particular concern is the routine IR exposure of children under 5 years of age, who are up to three times more likely to get cancer from IR exposure than adults age 25 [10]. The findings of several studies indicate that dental radiation does pose a risk of head and neck cancers [70], although the mortality risk is apparently very small: Only one in 10 million intraoral X-rays is estimated to result in a fatal cancer [71]. However, could a larger portion of pediatric patients — some of whom begin receiving dental IR when they are still toddlers — be at risk of subtle neurological effects, such as depression? There is evidence that loss of synaptic plasticity causes depression by disrupting the complex neurotransmissions that maintain balanced moods [69]. A troubling trend in depression among girls suggests this merits some consideration. The percentage of girls ages 12 to 17 experiencing a major depressive episode increased from 13.1 percent in 2004 to 17.3 percent in 2014, with no known previously identified socio-demographic, household, or substance-abuse factor that could explain it [72]. Although studies have found an association between depression and low-dose IR among those exposed in situations such as nuclear testing and plant accidents [73], the results must be interpreted with caution due to a lack of precise dose levels and confounding factors such as psychological stress.

Also potentially at risk: people with larger bodies

Obese people, who now make up more than one-third of the adult population, are another group that faces increased risk of IR exposure. Due to the need for IR to penetrate a greater tissue volume to obtain sufficient image resolution, obese patients receive significantly more IR exposure during diagnostic radiology than non-obese patients [74]. Interestingly, obesity in midlife is associated with a greater risk of dementia down the line than at other points in life, including the age of dementia diagnosis [2], an outcome that currently is little understood but may be related to the latency period of effects following low-dose IR exposure.

Testing the hypothesis

There are many ways to approach testing the hypothesis that low-dose IR increases the risk of neurodegeneration. One question worth investigating is whether bitewings, which are the most common type of dental radiograph, are associated with developing AD, which is the most common form of dementia. This is a question dental radiation experts who calculate IR angles, doses, scattering and tissue absorption can address in conjunction with neuroscientists who are familiar with the specific brain regions involved in each neurodegenerative disease.

Insurance companies that have helped pay for a lifetime of medical and dental care for covered individuals may now provide researchers with a treasure trove of appropriately anonymous data on the radiation histories of policy-holders subsequently diagnosed with neurodegeneration, as well as a pool of control subjects. Another resource might be military medical and dental records that could provide more complete histories than the scattered records of civilians who may be subject to frequent changes in health insurers and/or practitioners. Although there are many potentially confounding neurodegeneration risk factors involving deployed military personnel, such as traumatic brain injury [75], the records of non-deployed personnel may prove to be a valuable resource.

Specific diseases may provide investigators with unique opportunities to test the hypothesis. For instance, since women are much more radiosensitive than men [10] and have at least twice the incidence of MS [41], [54], it might be worth capturing complete IR histories of MS patients — including the timing of and relatively small amounts of dental and chiropractic exposures — to determine whether diagnostic radiation is a factor in the etiology and sometimes erratic progression of MS. Adding to the urgency is a worldwide increase in pediatric MS prevalence with up to 10 percent of patients manifesting disease onset prior to the age of 16. [76].

Testing the hypothesis also provides an opportunity to review existing information in a new light. For example, could X-ray imaging contribute to the proven yet poorly understood association of patients diagnosed with ALS having a history of bone fractures [77]? A review found this association was apparent even though face and head fractures were excluded to avoid potential confounding factors. Various possible causes were ventured, such as preexisting poor bone health, but the data did not fully support these conjectures. What was not taken into account was that people with bone fractures typically undergo a series of X-rays of the injury for both diagnostic purposes and to monitor healing. Across diseases there are countless other well-observed but little-understood facts that may reveal how and why they contribute to neurodegeneration when IR exposure is considered.

Another possible research avenue would involve taking a new approach to creating animal models of neurodegeneration. Currently, animal models are genetically engineered — an expensive undertaking that has yet to lead to the discovery of a pharmaceutical “golden bullet.” Would exposing animals to IR doses at levels and intervals consistent with dental protocols provide better research subjects?

Discussion

While it is puzzling that there are so many different forms of neurodegeneration in humans, a person’s risk could be as individual as the combination of genetic predisposition, gender, age at IR exposure, history of back pain treatment and dental plan, among other factors. Yet this situation may not be as complex as it seems, if simply removing or reducing man-made IR exposure would greatly reduce the risk of neurodegeneration. The fact that dental X-rays deliver very small amounts of radiation — compared, for instance, to therapeutic brain radiation — does not mean they are without long-term effects, especially when there are so many variables such as of the frequency of dental visits, number of X-rays taken, the type of equipment used and the safety measures employed, as well as age at the time of exposure, gender and body size. The increasing use of digital intraoral radiography has been heralded for reducing patient exposure, but extraoral radiography, especially CBCT radiography, can quickly offset any such gains. And just as humans, alone among primates, receive frequent head exposure to man-made radiation, so are today’s children and young adults the first to have undergone so much radiation at such a young age.

Although there are other environmental insults that can induce unnaturally high levels of ROS, dental IR deserves special consideration because it sends X-rays directly into the head, where neurodegeneration that does not originate in the spine occurs, and is commonly undergone by a great majority of the population throughout their lives. Symptom and pathological commonalities across neurodegenerative diseases suggest they may have a common etiology — especially in view of how little is understood about what causes the vast majority of cases.

This is not an easy issue. Diagnostic imaging is considered an indispensable tool in dentistry. Dentists rely on the diagnostic procedures they were taught to conduct, using the equipment they were trained to use, following guidelines provided by their professional organizations. Many people who undergo repeated head exposure to diagnostic X-rays do not develop neurodegeneration, but the percentage of unaffected people dwindles with every decade, even though neither dementia nor motor-neuron diseases are natural consequences of aging. If head exposure to low-dose IR increases the risk of neurodegeneration, all possible means of reducing exposure must be implemented and imaging protocols revised so that future generations can age with dignity, grace and understanding.

Declaration of Competing Interest

The author certifies having no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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