1. Centre for Ageing Research, Faculty of Health and Medicine, Lancaster University, Lancaster UK
2. High Lane Medical Practice, Stockport, UK
3. Sedbergh Medical Practice, Kendall, UK
4. Care Force Consulting, Frome, UK
5. Functional Again Medical Practice, Gisborne, NZ
Academic Editor: James S. Powers
Received: April 08, 2019 | Accepted: August 01, 2019 | Published: August 07, 2019
OBM Geriatrics 2019, Volume 3, Issue 3, doi:10.21926/obm.geriatr.1903066
Recommended citation: Chalfont G, Simpson J, Davies S, Morris D, Wilde R, Willoughby L, Milligan C. Personalised Medicine for Dementia: Collaborative Research of Multimodal Non-pharmacological Treatment with the UK National Health Service (NHS). OBM Geriatrics 2019;3(3):26; doi:10.21926/obm.geriatr.1903066.
© 2019 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
As many as one in three people born in 2015 in the UK will develop dementia in their lifetime , yet modifiable risk factors contribute to one-third of Alzheimer’s cases [2,3]. The dominant narrative around dementia argues that progression cannot be halted or reversed. Current treatment approaches, whether pharmacological or neuropsychological at best delay decline . Explosive headlines such as dementia being a ’ticking time-bomb’ and estimates of prevalence based on no change in treatment reinforce this account. However, evidence on multimodal non-pharmacological treatments (MM NPTs) formulated around a ‘personalised medicine’ approach challenges this view.
This paper introduces a novel approach to dementia treatment in the following sections:
- Dementia prevention - Current evidence on multimodal non-pharmacological treatments
- The logic of applying personalised medicine to dementia
- A Functional Medicine (FM) treatment approach – 6 Case Reports
- Discussion and Conclusion
To our knowledge, this paper contains the first case reports showing improved symptomatology of memory-impaired patients in the UK , as well as two in Greece and one in New Zealand. It also reports in some depth the approach to root cause analysis, including presentations, indications, evaluations, treatment recommendations, outcomes and follow-ups over time. The reports give variable depth and extent of patient information as determined by each practitioner. Research ethics approval was granted by the Faculty of Health and Medicine Research Ethics Committee [FHMREC17047].
2. Dementia Prevention – Current Evidence on Multimodal Non-Pharmacological Treatments
Rather than having a precise neurobiological cause, Alzheimer’s and other dementias represent a heterogeneous state, determined by multiple factors and mechanisms that interact and intervene throughout life [5,6]. Reduction of modifiable risks is currently the preferred strategy to reduce future cognitive decline. Modifiable risks include depression, sleep disturbances, smoking, obesity, hyperlipidemia, diabetes and hypertension. Remedial actions include further education, social engagement, cognitive training, Mediterranean diet, exercise and physical activity [7,8]. Primary prevention trials aim to reduce future prevalence by modifying such factors in healthy or at-risk populations . In at-risk elderly people, interventions modifying more than one factor have improved or maintained cognitive functioning  and seem feasible, cost-effective and engaging .
Increasingly, studies investigate secondary or tertiary prevention and seek to interrupt cognitive decline or dementia that is already underway . Once a person experiences measurable cognitive impairment and receives a diagnosis, treatment interventions could potentially be more effective, because the person retains insight. Such studies are promising, tend to show a benefit with the intervention group compared to the controls and tend towards higher reporting quality . An example is the Body, Brain, Life for Cognitive Decline (BBL-CD) RCT providing a multidomain lifestyle intervention to people with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Australian primary care . The intervention included on-line education and personal sessions on exercise, diet, nutrition, cognitive engagement, brain training and physical activity. All the studies above utilised examples of therapies that are not pharmacological.
Non-pharmacological therapies (NPTs) are a ‘useful, versatile and potentially cost-effective approach to improve outcomes and QoL’ in Alzheimer’s disease (AD) and related disorders for both the person with dementia and caregivers . Single-domain interventions (nutritional supplements, cognitive training and physical activity) for individuals with positive biomarkers and cognitive impairment have been shown to be protective of cognitive decline . Physical activity also appears to benefit various aspects of cognition including stabilization of MMSE scores, improved attention, memory and recognition [16,17], the ability to perform ADLs and overall well-being . For people with cognitive decline or early dementia, NPTs have successfully addressed sleep, yoga, exercise and nutrition [19,20,21,22] among other domains. Cognitive decline can be attenuated by factors such as improved nutrition, appropriate dietary supplementation, increased physical exercise, mental exercise and social activities .
Evidence from multimodal studies elucidates possible synergistic effects. Exercise, in combination with dietary factors has been demonstrated to affect molecular events related to the management of energy metabolism and synaptic plasticity . Randomised controlled trials (RCTs) of multimodal interventions find that community-dwelling cognitively impaired elders benefit from combining physical, cognitive and social activities . Evidence suggests that multiple therapeutic approaches (nutritional, botanical and stimulatory) targeting several dysfunctions at once may offer the most benefit with fewer adverse consequences than conventional medications . In a 12-week intervention for people with MCI involving diet, omega-3 supplements, physical activity, cognitive stimulation, neurofeedback and meditation, 84% significantly improved cognitive function and 53% showed hippocampal growth . The multimodal approach may thus be effective for improving cognitive function  and for maintaining or improving cognitive health , for persons with mild cognitive impairment (MCI) or dementia . However, randomly assigned interventions to treat memory complaints with a multidomain intervention and polyunsaturated fatty acids, either alone or in combination, revealed no significant effects on cognitive decline over 3 years , which may support arguments for a personalised approach.
A recent systematic review on multimodal non-pharmacological interventions to improve cognition for people with dementia  noted that group studies used 2-3 modes of intervention and multiple methods to implement them. Interventions utilised included cognitive, physical, psychological and psychosocial, nutrition, fasting, gut health, sleep hygiene, stress reduction, detoxification, hormonal health and oxygen therapy. In 19 (90%) of the 21 group comparisons, participants were reported to have cognitive improvements, stability with their dementia or a delay in their decline. However, persons treated individually in the five case studies achieved the most clinically effective results. Each personalised patient treatment utilised in-depth assessments and prescribed up to nine different modes. In cases where cognitive outcomes were improved, studies leveraged recent advances in our understanding of the underlying causes of dementia and ways to disrupt these neurodegenerative mechanisms. Furthermore, personalised one-to-one interactions specific to each individual involving investigation and assessment by the clinician, helped to focus or fine-tune the intervention.
3. The Logic of Applying Personalised Medicine to Cognitive Decline and Dementia
Personalised medicine addresses chronic disease with a holistic lifestyle approach common to Eastern mind-body-spirit traditions, which emphasise prevention rather than treatment, and focus on the person instead of the disease . Lifestyle recommendations include healthy eating, active living, healthy weight and emotional resilience. A sub-optimal lifestyle is associated with the development and prognosis of long-term conditions. An individual’s health metrics (laboratory tests, functional biomarkers and other diagnostics) are used to design patient-specific prescriptions for diet, exercise, stress and environment. In this way, lifestyle medicine-oriented therapeutic strategies can improve individual health outcomes and manage chronic disease [33,34,35].
Underlying this approach is the bodily process of homeostasis whereby the body self-regulates to changes within or outside the system to maintain a dynamic state of equilibrium called health , also formulated as ‘the ability to adapt and self manage’ . Normal mental function depends on a balance between synaptoblastic (synapse-making) and synaptoclastic (synapse-destroying) activity . When maintenance is unbalanced by deficiencies or pollutants, cells cannot be replaced and synaptoclastic processes win, resulting in cognitive decline. By correcting the environment to support healthy growth and repair while reducing toxins and infections, cells can rejuvenate.
To illustrate this point, consider current findings concerning amyloid-beta protein (Aβ), the primary pathological biomarker of Alzheimer’s disease. Why it accumulates is of growing interest. Studies suggest β-amyloid deposition is an early innate immune response to infections acting as an antimicrobial peptide . This antimicrobial role suggests inflammation propagates AD neurodegeneration, and immune pathways mediate pathogen entrapment and protect against infection . Amyloid protein may also be evidence of an innate response to destroy fungal colonization . Furthermore, we have yet to solve the ‘Amyloid Paradox’, whereby senile plaques composed of Aβ contain substantially elevated levels of iron, copper and zinc which bind to the Aβ making it toxic to neurons. On the other hand, Aβ can reduce the neurotoxicity of metal ions, suggesting that the interaction can under some circumstances be protective. In studies where iron or copper were combined with Aβ, the neurotoxicity of these metals was substantially reduced, assisting the antioxidant defense of the brain . Efforts to support plaque removal need to be guided by a better understanding of its protective role, and the imbalance of Aβ production versus destruction . This gives one more reason to promote neurogenesis by supporting the body’s natural equilibrium.
A personalised and programmatic therapeutic approach called Metabolic Enhancement for Neurodegeneration (MEND) has demonstrated the reversal of cognitive decline in patients with early AD . This comprehensive precision medicine approach used clinical information and metabolic profiling of AD individuals, and provided additional objective evidence that this programmatic approach to cognitive decline is highly effective and may enhance pharmaceutical efficacy . In some patients, modifications to daily activities, diet, exercise, stress, sleep, etc. can mitigate dementia symptoms such that a clinical diagnosis of dementia is no longer justified . From the perspective of patient and caregivers, this alone may greatly improve quality of life and wellbeing. Over 100 case studies have now reported improvement in cognition, with some cases presenting electrophysiology or imaging of morphological structure as well as recovery of functional neurocognitive status [47,48].
Personalised multimodal medicine (aka holistic , natural  or FM  as a ‘whole systems’ approach  is therefore logically suited to address cognitive decline or dementia because it identifies individual causative factors through in-depth investigation and root cause analysis. The practitioner asks not “What?” but “Why?” and prescribes an intervention as a ‘disease modifying therapy’ (DMT) that targets change in the underlying disease process leading to cell death . The mechanisms and determinants are many  and predominantly involve nutritional deficiency , inflammation , oxidative stress , mitochondrial dysfunction , impaired methylation pathways , impaired Aβ clearance , hormone imbalance , chronic stress , gut dysbiosis , insulin dysregulation , infections [40,63,64,65,66], poor sleep , vascular disease , and toxicity [41,60,69,70], including heavy metals [71,72,73,74,75].
Recommendations to address these include diet and nutrition [22,76] with an emphasis on healthy diets such as the Mediterranean, DASH, MIND and plant-based diets, whole foods, vegetables and fruits, probiotics, antioxidants, nuts and seeds and Omega-3 fatty acids [77,78,79] and nutritional support [80,81,82]. Recent findings support a low carbohydrate, high fat diet in which saturated fats (olive oil, butter, coconut oil) are advised over manufactured fats and seed oils [83,84,85]. The ketogenic diet [86,87] and medium-chain triglycerides (MCTs) are also recommended . Further recommendations include exercise [88,89,90], stress reduction, fasting [91,92], cognitive stimulation and sleep hygiene .
Having first summarised the current evidence on MM NPTs we then explained the logic of applying personalised medicine to dementia. In what follows, we draw on 6 patient case reports to demonstrate how practitioners are operationalising this personalised FM approach to the treatment of their patients with cognitive decline, Alzheimer’s and other dementias. To clarify, cognitive decline or cognitive impairment are terms used to describe symptoms that may or may not precede dementia. The evidence is inconclusive as to any correlation between such symptoms and dementia, as the standards of proof can never be ethically met . However, in the following case reports, patients presented with some form of cognitive impairment, decline or memory issues, most of which had progressed to a dementia.
These case reports are novel in showing marked improvement in symptoms for what is currently by conventional medicine considered an irreversible condition. These reports are not case studies, ie, not research exercises with a specified treatment period, treatment protocol and target outcomes. They provide instead a brief description of the patient’s clinical and demographic details, the diagnosis, any interventions and the outcomes as specified in the BMC Medical Research methodology  and the CARE  guidelines. Importantly, these findings shed new light on the possible pathogenesis of the disease which may, based on publication of these and similar early patient reports [47,48], prove to be ultimately treatable with this novel ‘root cause’ analysis approach.
4. Functional Medicine (FM) Treatment Approach - 6 Case Reports
As with other personalised medicine (holistic, integrative or natural) treating the person is paramount to treating a particular problem. FM  is a systems biology–based approach that focuses on identifying and addressing the root causes of disease.
Practitioners use low-risk interventions that modify molecular and cellular systems to reverse the drivers of disease. The FM approach is particularly useful for treating a disorder like cognitive impairment, where one condition can be driven by many causes. Cognitive impairment is driven by inflammation, insulin resistance, gut dysbiosis, metabolic syndrome, nutrient deficiencies, toxicity, infections, and so on (Figure 1). The underlying causes are also interlinked and respond to similar mechanisms. So treating one of the causes may synergistically alter and improve another. www.ifm.org
Figure 1 Identified drivers of cognitive impairment.
Those with memory and concentration problems tend to belong to one of several categories of presentation:
- Many have chronic fatigue symptoms with both physical and mental fatigue (often described as ‘brain fog’). As the brain consumes around 22% of the energy created by the body per day, anything leading to lack of energy production will inevitably impact on cognitive processing. This can be associated with unusual neurological symptoms such as blurred vision, tinnitus and pain syndromes / fibromyalgia.
- Some patients have cognitive dysfunction linked to toxicity - often due to genetic or acquired chemical processing issues. These can lead to severe side effects where other individuals with similar exposure may suffer no effects. Many of these patients have accompanying chemical sensitivities and are unable to tolerate volatile organics or even perfumes. Examples include those with ammonia overload (from trans-sulphuration pathway defects and bacterial overgrowth), and patients with exposures to heavy metals accompanied by poor metals elimination processing.
- Some have endocrine dysfunction which has not been recognised or adequately treated. Hypothyroidism is a common presentation – when untreated this leads to fatigue, low mood, poor concentration and metabolic syndrome.
- Some have specific nutritional deficits leading to poor metabolism and malfunctioning mitochondria, poor methylation capacity or neurological damage. Unrecognised B12 deficiency, folate deficiency and metabolic problems with folate and B12 are common causes of neuro-cognitive malfunction. This can lead to peripheral neuropathy, pain syndromes, low mood, poor concentration, insomnia and memory losses. Due to the difficulty of identifying B12 metabolism disorders in some patients, a course of B12 injections will be routinely trialled with any patient with neurocognitive dysfunction, fatigue or peripheral neuropathy. However, where possible they will be screened for serum B12, methylmalonic acid and homocysteine levels first.
- Other miscellaneous syndromes presenting with subjective cognitive dysfunction include those with intractable insomnia, severe mood disorders and specific drugs (opiates, anti-epileptics / nerve pain-killers).
Many of these categories will overlap (patients often have low B12, Vitamin D deficiency and Hypothyroidism for example). This indicates the importance of looking for all underlying contributing factors and addressing them to give the patient the best chance of recovery.
FM practitioners proceed with a detailed intake process and dietary analysis (captured in a lengthy, in-depth questionnaire). In addition to routine haematology, biochemistry, hormone levels, HbA1c and thyroid screen, some advanced functional testing is arranged to establish the potential contributors to cognitive decline. Patients with neuro-cognitive problems and/or fatigue are generally screened for:
- Hypothyroidism and T4 to T3 conversion disorder (T4 and T3 are hormones containing iodine, that are produced by the thyroid gland. The thyroid produces mainly T4, which is then converted to T3, in tissue and organs. T3 is the active hormone.)
- B12 and folate deficiencies / metabolism disorders
- All other B vitamin deficiencies
- Vitamin D deficiency
- Iron deficiency / overload / anaemia
- High ammonia / nitrogen overload
- Miscellaneous metabolic disorders (with organic acids)
- Possible contributing medications / supplements
- Risk factors for toxicity / heavy metals exposure (all screened for dental amalgam) / mold
- GI map genetic stool test and Small Intestine Bacterial Overgrowth (SIBO) breath test
- Home "burp" test to assess adequacy of stomach acid
- DUTCH (urine and saliva based) adrenal and hormone testing
- Yeast and bacterial overgrowth (organic acid testing)
- Chronic viral screen; Oral and nasal swabs; Candida questionnaire; Allergies
They may also consider testing salivary cortisol levels and ordering a hair analysis for heavy metals. Blood tests determine the need for vitamin support, blood glucose support and thyroid support. (Patients on warfarin are not given Vitamin D with K2.) A homocysteine blood test is used for B vitamin support with folate, B12 and B6. Adrenal support (fatigue, anxiety) and sleep support supplements depend on the questionnaire. After the first 8 weeks neurotrophic support can be added with Bacopa monnieri and Lion’s mane mushroom. Detox support depends on the hair analysis. One must wait 2-3 months before detoxing.
Upon receiving test results the practitioner analyses these data to determine what processes are compromised by what mechanism or input. The aim is to identify the root causes of the disturbance and adjust the process through lifestyle and supplements, in order for the body to regain homeostasis.
4.3 Case Reports
Six case reports are given from four medical practitioners involving patients with cognitive decline and/or a formal diagnosis of a dementia. All patients gave informed consent to the practitioners for their data to be included. Patient reports are summarised in Table 1.
Table 1 Case reports of patients with cognitive decline or a dementia treated with FM.
4.4 Key Points, Insights and Findings
The 11 key points below summarise some insights gained, and tentative findings from these six case reports. By looking at cognitive impairment as one small piece of a larger puzzle these key points further illustrate the unique and potentially beneficial aspects of this treatment approach.
1. Not just a memory problem – Dementia is not a solitary problem of memory but is often one of a mixture of conditions and part of wider health issues. Lifestyle appropriate for addressing dementia has positive side-effects on other conditions.
2. Never too late to start – [CS1 – Case Study 1] A male in his mid 90s is very weak and frail, cannot walk and requires 24-hour assistance with all ADLs from a son with whom he lives. After an in-depth investigation by the FM practitioner, the son initiated dietary changes, further supplements and an exercise regime. “He has begun to help me a bit more than before when I ask him to move an arm or lift a leg or bend forward. If his brain is slowly waking up it must be difficult for him - to more fully realise his circumstances. He improves most after a fasting episode.”
3. Success requires family support – [CS1] “Bananas brought on a relapse a month ago when I gave him banana every day for about a week - it ended with him not recognising me.” “Relapses occur when I get tired of trying to help him or when I try too hard.” “Exercise is very important. As well as exercising his legs with a Reck MOTOmed I have now got him a Motovator Medidrive - which bicycles his hands and arms. He has been using that for a week and the difference is noticeable.” “I have been trying to take him swimming as often as I can, but the last time was two weeks ago. The sheer effort of it puts me off - but it is very good for him. Best would be every day...!” “I am now including five of Bredesen’s  Indian herb supplements, as well as the ones you recommended. I think they are making a difference. Probably an important difference.”
4. Nutrient deficiencies – Each case had abnormal nutrient levels with implications for brain health. “Profoundly deficient in selenium (red cell analysis), Vitamin D insufficiency 39ng/ml (optimum 50-80ng/ml), suboptimal vitamins B5 & B6, Vitamin C.”[CS3] “PPIs (proton pump inhibitors) & Metformin cause low B12.”[CS2] There is a role therefore, for B12 injections to be started right away with all memory problems. Patients can easily be taught to self-inject. Nutritional support is also needed for methylation, or run the “risk of recurring cognitive impairment” [CS2]. “Curcumin is anti-inflammatory. Magnesium ascorbate provides antioxidant support, and Magnesium threonate crosses the blood brain barrier effectively.” [CS5].
5. Prescription medications – “Opiates and Pregabalin may result in mitochondrial dysfunction with fatigue, cognitive dysfunction and inability to regulate autonomic nervous system.”[CS2] Pregabalin side effects include sleepiness, confusion and memory impairment. Statins cause mitochondrial dysfunction. PPIs (proton pump inhibitors) reduce acid formation in the stomach to prevent ulcers, but long term PPI use has been linked to dementia and vitamin B12 deficiency. Beta blockers (beta-adrenergic blocking agents) block adrenaline from binding to beta receptors on nerves; act to reduce heart rate/blood pressure by dilating blood vessels) (see CS5 about dropping these).
6. Mis/undiagnosed/untreated/under-treated thyroid function – “Probable longstanding ‘subclinical hypothyroidism’ may well have contributed to weight gain, metabolic syndrome and diabetes.”[CS2] “Type II or Atrophic AD is due to under-treated hypothyroidism, decreased cerebral perfusion due to too much beta blocker medication, and lack of several key nutrients.”[CS5] “Low selenium and zinc would impact thyroid function.”[CS4].
7. Toxicity, heavy metals, pesticides, infection – Mercury exposure from dental amalgams was evident in half of the cases, whereas chemotherapy [CS4] or other chemotoxic loads (pesticides, lab chemicals, smoking, ETOH, glyphosate, petrochemicals, agrochemicals) or heavy metals (mercury, aluminium, tin, arsenic) were evident in all cases. “Oral health was suboptimal with many missing teeth, multiple amalgam restorations and considerable periodontitis and hard and soft plaque.” [CS4]; “Low glycine and glutathione would impair detox pathways.”[CS5]
8. Connection to diabetes – “Worked with GP to come off insulin as this was causing weight gain and carb cravings to worsen.”[CS2] “Early insulin resistance - from high carbohydrate (CHO) diet contributes to inflammation.”[CS5].
9. Gut-Brain connection – stomach acid and beneficial bacteria – Low stomach acid and low digestive enzymes [CS5]; There is a requirement for digestive support for low levels of beneficial bacteria, as some “(o)pportunistic bacterial overgrowth would impact ability to extract nutrients from food.”[CS5].
10. Dehydration and fasting – [CS1] “(my father) improves most after a fasting episode.” “Total body water was significantly reduced at 32.8 l (predicted optimal 36-43 l)”[CS5].
11. Metabolic syndrome presents continued risk for cognitive impairment – “Likely to remain at risk of recurring cognitive impairment without continued attention to reducing metabolic syndrome and nutritional support for methylation.”[CS2].
These observations provide further support to the growing body of case reports describing reversal of cognitive decline in patients with early Alzheimer’s or other dementias. To our knowledge, this is the first paper reporting practitioner case reports documenting improvements in symptomatology of memory decline in patients from the UK, Greece and New Zealand. Four patients had their initial presentations and follow-up improvements verified by MoCA and/or a formal diagnosis, and two patients had symptom improvements verified through self-report and proxy-report.
Improvements were shown through biomarkers, such as normalisation of serum levels, folate and homocysteine, thyroid function, blood sugar levels, as well as weight loss, decreased blood pressure and reduction in medications (beta-blockers, statins, insulin, metformin, pregabalin and painkillers).
Improvements were also reported in: cognitive function, memory, visuospatial ability, delayed recall, attention, orientation, overall health, physical strength, communication, clarity, mood, emotions, feeling hopeful for the future, lifting of brain fog, energy levels, a bit more awake, reading, ability to meditate, doing Sudoku, going out, socialising, looking after grandchildren, going for walks, helping with chores, visiting family, interacting, engagement in conversation and making insightful comments and suggestions.
A small but growing body of evidence illustrates through N-of-1 case studies or case reports the process, practice and progress of patients presenting with cognitive decline. This paper has contributed a few more. Limitations are many. The particular analyses and interventions are not uniform across the practitioners, nor were consistent measures taken at baseline and beyond. There was no uniformity of diagnoses, except that a clear presence of cognitive decline was reported, measured or diagnosed. Further limitations of case reports include sample size (n=1) and lack of control or randomisation. In the case of any treatment for dementia, ‘usual care’ spells ultimate decline [98,99] acting as a control whereby any stability in symptoms or delay in decline can be interpreted as improvement [100,101]. Furthermore, as this is a multimodal intervention involving a wide range of treatments, it is impossible to correlate improvement with any one mode. As this is not mono-therapy drug research, there is no need or intention to isolate any particular intervention. If a mono-therapy could treat dementia it would be marketed already. The multi-domain nature of dementia and the multimodal treatments of IM practitioners advocate for a medical paradigm shift towards an ecological model where health is determined by a complex interaction of factors at different levels, including the realms of energy  and intent .
There is also an epistemological argument to be made whereby empiricism concerns only knowledge gained through sense experience. Most energy medicine operates beyond the narrow bandwidths of human sensing and is often dismissed as scientifically impossible simply because modern empirical science, and therefore conventional medicine fails to understand it. This is blaming a fish for not being able to ride a bicycle. But this is slowly changing as technology evolves to record, measure and verify the body’s energy field or ‘biofield’ . The biofield is a ‘multilevel organizational concept in which information flows within and between the various levels of the organism’ . Biofield therapy  is non-invasive and involves practitioner interactions with the client’s biofields, interacting fields of energy and information both within and around living systems [105,106,107], capturing an “aspect of healing beyond limited implication of medicine as a treatment for illness,”  but also in clinical studies reducing pain, negative behavioural symptoms in dementia and anxiety in hospitalised populations [108,109]. The possibilities are staggering - “The ability to understand and control shape in its most general form offers the opportunity to address a wide range of biomedical problems and restore complex structures damaged by injury, cancer, disease or age.” [105.]
With these case reports, regardless of which mode was most efficacious, an outcome of improvement for the patient is our optimal concern. These findings lend further supportive evidence to silence the dominant narrative that dementia is incurable and irreversible.
5.1 Future Directions
We advocate for personalised medicine within the UK National Health Service (NHS) for persons living with memory problems and dementia . Approaching a chronic multifactorial condition in this manner is relatively new to the UK, but attracting attention elsewhere . A ‘root cause’ FM approach to cognitive decline or dementia is not available through the NHS, nor is it clear as to the extent of global availability. Practitioners are being trained around the world and starting private practice, but we are unaware of any present government health service provision. The availability of FM practitioners motivates resourceful individuals to implement multiple difficult lifestyle changes, subsequently contributing data to case reports, as above.
There is a pressing need for interventions that can modify the disease process and affect measurable improvement in cognition and associated benefits to quality of life for patients and caregivers. We therefore aim to draw upon the latest evidence, learn from existing projects worldwide and develop the next phase of the work: a logistically practical, affordable, holistic, enhanced intervention alongside the existing NHS memory service pathway. However, lifestyle change can be difficult for older people as it may involve changing or relinquishing cherished habits and routines, as well as challenging long-held perceptions and beliefs around dementia, its causes and the possibility of change through treatments. Crucially, in designing the intervention protocol, we aim to assist participants and their caregivers to overcome the major physical, emotional, environmental and psychological hurdles associated with behaviour change . To facilitate this goal, substantial engagement with people with early-stage dementia, caregivers and practitioners is ongoing.
Existing evidence and workable protocols emerging from personalised medicine regarding the arrest and reversal of cognitive decline in symptomatic individuals opens a new window for research and care practice. The suitability of this approach to dementia is evident given the multiple causative factors identified to date. Personalised multimodal medicine provides a potent cocktail targeting several individual causative factors through in-depth investigation and root cause analysis, resulting in the disruption of neurodegenerative mechanisms. Although this systems approach seems novel and ground-breaking, it merely reinforces ancient mind-body-spirit traditions of treating the person, not the disease, by way of energy that contributes information for a person’s mental, emotional, physical, and spiritual wellbeing . Such practices continue to sustain lives around the world today.
The window of opportunity for intervention is when subjective impairment or early-stage dementia renders the person both aware of their circumstance and cognitively able to address it. A proposed collaborative project between Lancaster University and the NHS in the UK will offer an enhanced level of intervention alongside the existing NHS memory assessment service pathway. Support for lifestyle change will be perhaps the most critical factor in success for these patients - helping them to overcome the major physical, emotional, environmental and psychological hurdles they will face.
Beyond the paradigm of ‘living well with’ dementia, existing treatment protocols are facilitating a future whereby people with dementia and their loved ones can ‘live well beyond’ diagnosis.
SD, DM, RW and LW provided patient case reports and treatment protocols. GC conducted the research and drafted the paper. CM and JS are the PI and Co-I on this project respectively. Both have been involved in the running of the project, data analysis and reading and commenting on drafts of the paper.
This research was supported by the AIM Foundation.
The authors have declared that no competing interests exist.
- Lewis F. Estimation of future cases of dementia from those born in 2015; consultation report for Alzheimer’s research uk. Alzheimers Res UK. 2015.
- Kulmala J, Ngandu T, Kivipelto M. Prevention matters: Time for global action and effective implementation. J Alzheimers Dis. 2018; 64: S191-S198. [CrossRef]
- Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet. 2017; 390: 2673-2734. [CrossRef]
- Wollen KA. Alzheimer’s disease: The pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev. 2010; 15: 223-244.
- Van der Linden M, Juillerat Van der Linden AC. A life-course and multifactorial approach to Alzheimer’s disease: Implications for research, clinical assessment and intervention practices. Dementia (London). 2018; 17: 880-895. [CrossRef]
- Keine D, Walker JQ, Kennedy BK, Sabbagh MN. Development, application, and results from a precision-medicine platform that personalizes multi-modal treatment plans for mild Alzheimer’s disease and at-risk individuals. Curr Aging Sci. 2018; 11: 173-181. [CrossRef]
- Lehert P, Villaseca P, Hogervorst E, Maki PM, Henderson VW. Individually modifiable risk factors to ameliorate cognitive aging: A systematic review and meta-analysis. Climacteric. 2015; 18: 678-689. [CrossRef]
- Baumgart M, Snyder H, Carrillo M, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimers Dement. 2015; 11: 718-726. [CrossRef]
- Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (finger): A randomised controlled trial. Lancet. 2015; 385: 2255-2263. [CrossRef]
- Toman J, Klimova B, Valis M. Multidomain lifestyle intervention strategies for the delay of cognitive impairment in healthy aging. Nutrients. 2018; 10. doi: 10.3390/nu10101560. [CrossRef]
- Vilela VC, Pacheco RL, Latorraca COC, Pachito DV, Riera R. What do cochrane systematic reviews say about non-pharmacological interventions for treating cognitive decline and dementia? Sao Paulo Med J. 2017; 135: 309-320. [CrossRef]
- Horr T, Messinger-Rapport B, Pillai JA. Systematic review of strengths and limitations of randomized controlled trials for non-pharmacological interventions in mild cognitive impairment: Focus on Alzheimer’s disease. J Nutr Health Aging. 2015; 19: 141-153. [CrossRef]
- McMaster M, Kim S, Clare L, Torres SJ, D'Este C, Anstey KJ. Body, brain, life for cognitive decline (bbl-cd): Protocol for a multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment. Clin Interv Aging. 2018; 13: 2397-2406. [CrossRef]
- Olazaran J, Reisberg B, Clare L, Cruz I, Pena-Casanova J, Del Ser T, et al. Nonpharmacological therapies in Alzheimer’s disease: A systematic review of efficacy. Dement Geriatr Cogn Disord. 2010; 30: 161-178. [CrossRef]
- Andrieu S, Coley N, Lovestone S, Aisen PS, Vellas B. Prevention of sporadic Alzheimer’s disease: Lessons learned from clinical trials and future directions. Lancet Neurol. 2015; 14: 926-944. [CrossRef]
- Groot C, Hooghiemstra AM, Raijmakers PG, van Berckel BN, Scheltens P, Scherder EJ, et al. The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Res Rev. 2016; 25: 13-23. [CrossRef]
- Lee J. The relationship between physical activity and dementia: A systematic review and meta-analysis of prospective cohort studies. J Gerontol Nurs. 2018; 44: 22-29. [CrossRef]
- Ruthirakuhan M, Luedke AC, Tam A, Goel A, Kurji A, Garcia A. Use of physical and intellectual activities and socialization in the management of cognitive decline of aging and in dementia: A review. J Aging Res. 2012; 2012: 384875. [CrossRef]
- Brenes GA, Sohl S, Wells RE, Befus D, Campos CL, Danhauer SC. The effects of yoga on patients with mild cognitive impairment and dementia: A scoping review. Am J Geriatr Psychiatry. 2019; 27: 188-197. [CrossRef]
- Gibson RH, Gander PH, Dowell AC, Jones LM. Non-pharmacological interventions for managing dementia-related sleep problems within community dwelling pairs: A mixed-method approach. Dementia (London). 2017; 16: 967-984. [CrossRef]
- de Wilde MC, Vellas B, Girault E, Yavuz AC, Sijben JW. Lower brain and blood nutrient status in Alzheimer’s disease: Results from meta-analyses. Alzheimers Dement. 2017; 3: 416-431. [CrossRef]
- Solfrizzi V, Agosti P, Lozupone M, Custodero C, Schilardi A, Valiani V, et al. Nutritional interventions and cognitive-related outcomes in patients with late-life cognitive disorders: A systematic review. Neurosci Biobehav Rev. 2018; 95: 480-498. [CrossRef]
- Miquel S, Champ C, Day J, Aarts E, Bahr BA, Bakker M, et al. Poor cognitive ageing: Vulnerabilities, mechanisms and the impact of nutritional interventions. Ageing Res Rev. 2018; 42: 40-55. [CrossRef]
- Gomez-Pinilla F. The combined effects of exercise and foods in preventing neurological and cognitive disorders. Prev Med. 2011; 52: S75-S80. [CrossRef]
- Bae S, Lee S, Lee S, Jung S, Makino K, Harada K, et al. The effect of a multicomponent intervention to promote community activity on cognitive function in older adults with mild cognitive impairment: A randomized controlled trial. Complement Ther Med. 2019; 42: 164-169. [CrossRef]
- Fotuhi M, Lubinski B, Trullinger M, Hausterman N, Riloff T, Hadadi M, et al. A personalized 12-week "brain fitness program" for improving cognitive function and increasing the volume of hippocampus in elderly with mild cognitive impairment. J Prev Alzheimers Dis. 2016; 3: 133-137.
- Law LLF, Barnett F, Yau MK, Gray MA. Effects of combined cognitive and exercise interventions on cognition in older adults with and without cognitive impairment: A systematic review. Ageing Res Rev. 2014; 15: 61-75. [CrossRef]
- Fessel MM, Mann M, Miyawaki CE, Rosenberg DE. Multi-component interventions and cognitive health: A scoping review. J Gerontol Nurs. 2017; 43: 39-48. [CrossRef]
- Karssemeijer EGA, Aaronson JA, Bossers WJ, Smits T, Olde Rikkert MGM, Kessels RPC. Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis. Ageing Res Rev. 2017; 40: 75-83. [CrossRef]
- Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (mapt): A randomised, placebo-controlled trial. Lancet Neurol. 2017; 16: 377-389. [CrossRef]
- Chalfont G, Milligan C, Simpson J. A mixed methods systematic review of multimodal non-pharmacological interventions to improve cognition for people with dementia. Dementia (London). 2018. doi: 10.1177/1471301218795289. [CrossRef]
- Pizzorno JE, Murray MT, Joiner-Bey H. The clinician's handbook of natural medicine. 3rd ed: Elsevier; 2016. P. 992.
- Bodai BI, Nakata TE, Wong WT, Clark DR, Lawenda S, Tsou C, et al. Lifestyle medicine: A brief review of its dramatic impact on health and survival. Perm J. 2018; 22: 17-25. [CrossRef]
- Bland J. Mild cognitive impairment, neurodegeneration, and personalized lifestyle medicine. Integr Med (Encinitas). 2016; 15: 12-14.
- Minich DM, Bland JS. Personalized lifestyle medicine: Relevance for nutrition and lifestyle recommendations. Scientific World Journal. 2013; 2013: 129841. [CrossRef]
- Murthy MRV, Ranjekar P, K. , Ramassamy C, Deshpande M. Scientific basis for the use of indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: Ashwagandha. Cent Nerv Syst Agents Med Chem. 2010; 10: 238-246. [CrossRef]
- Huber M, Knottnerus JA, Green L, van der Horst H, Jadad AR, Kromhout D, et al. How should we define health? BMJ. 2011; 343: d4163. [CrossRef]
- Bredesen DE, John V. Next generation therapeutics for Alzheimer’s disease. EMBO Mol Med. 2013; 5: 795-798. [CrossRef]
- Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, et al. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PloS One. 2010; 5: e9505. [CrossRef]
- Moir RD, Lathe R, Tanzi RE. The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimers Dement. 2018; 14: 1602-1614. [CrossRef]
- Parady B. Innate immune and fungal model of Alzheimer’s disease. J Alzheimers Dis Rep. 2018; 2: 139-152. [CrossRef]
- Bishop G, Robinson SR. The amyloid paradox: Amyloid‐β‐metal complexes can be neurotoxic and neuroprotective. Brain Pathol. 2006; 14: 448-452. [CrossRef]
- Wildsmith KR, Holley M, Savage JC, Skerrett R, Landreth GE. Evidence for impaired amyloid β clearance in Alzheimer’s disease. Alzheimers Res Ther. 2013; 5: 33. [CrossRef]
- Bredesen DE, Rao RV. Ayurvedic profiling of Alzheimer’s disease. Altern Ther Health Med. 2017; 23: 46-50.
- Bredesen DE, Amos EC, Canick J, Ackerley M, Raji C, Fiala M, et al. Reversal of cognitive decline in Alzheimer’s disease. Aging. 2016; 8: 1250-1258. [CrossRef]
- Fischer P, Jungwirth S, Hinterberger M, Weissgram S, Krampla W, Leitha T, et al. 'Reversible' Alzheimer’s disease? J Am Geriatr Soc. 2011; 59: 1137-1138.
- Bredesen DE, Sharlin K, Jenkins D, Okuno M, Youngberg W, Cohen SH, et al. Reversal of cognitive decline: 100 patients. J Alzheimers Dis Parkinsonism. 2018; 8: 1-6. [CrossRef]
- Prokopov AF. A case of recovery from dementia following rejuvenative treatment. Rejuvenation Res. 2010; 13: 217-219. [CrossRef]
- Sharma R, Kabra A, Rao MM, Prajapati PK. Herbal and holistic solutions for neurodegenerative and depressive disorders: Leads from ayurveda. Curr Pharm Des. 2018; 24: 2597-2608. [CrossRef]
- Richer AC. Functional medicine approach to traumatic brain injury. Med Acupunct. 2017; 29: 206-214. [CrossRef]
- Tang Y, Lutz MW, Xing Y. A systems-based model of Alzheimer’s disease. Alzheimers Dement. 2019; 15: 168-171. [CrossRef]
- Cummings J, Fox N. Defining disease modifying therapy for Alzheimer’s disease. J Prev Alzheimers Dis. 2017; 4: 109-115.
- Kostoff RN, Zhang Y, Ma J, Porter AL, Buchtel HA. Prevention and reversal of Alzheimer’s disease. Georgia Institute of Technology. 2017.
- Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin d concentrations in Alzheimer’s disease: A systematic review and meta-analysis. J Alzheimers Dis. 2013; 33: 659-674. [CrossRef]
- Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, et al. Low-grade inflammation, diet composition and health: Current research evidence and its translation. Br J Nutr. 2015; 114: 999-1012. [CrossRef]
- Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H. Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Front Pharmacol. 2018; 9: 1162. [CrossRef]
- Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med. 2008; 10: 291-315. [CrossRef]
- Troesch B, Weber P, Mohajeri MH. Potential links between impaired one-carbon metabolism due to polymorphisms, inadequate b-vitamin status, and the development of Alzheimer’s disease. Nutrients. 2016; 8. [CrossRef]
- Janicki SC, Schupf N. Hormonal influences on cognition and risk for Alzheimer’s disease. Curr Neurol Neurosci Rep. 2010; 10: 359-366. [CrossRef]
- Justice NJ. The relationship between stress and Alzheimer’s disease. Neurobiol Stress. 2018; 8: 127-133. [CrossRef]
- Jiang C, Li G, Huang P, Liu Z, Zhao B. The gut microbiota and Alzheimer’s disease. J Alzheimers Dis. 2017; 58: 1-15. [CrossRef]
- Craft S, Cholerton B, Baker LD. Insulin and Alzheimer’s disease: Untangling the web. J Alzheimers Dis. 2013; 33: S263-S275. [CrossRef]
- Miklossy J. Emerging roles of pathogens in alzheimer disease. Expert Rev Mol Med. 2011; 13: e30. [CrossRef]
- Harris SA, Harris EA. Herpes simplex virus type 1 and other pathogens are key causative factors in sporadic Alzheimer’s disease. J Alzheimers Dis. 2015; 48: 319-353. [CrossRef]
- Carbone I, Lazzarotto T, Ianni M, Porcellini E, Forti P, Masliah E, et al. Herpes virus in Alzheimer’s disease: Relation to progression of the disease. Neurobiol Aging. 2014; 35: 122-129. [CrossRef]
- Eimer WA, Vijaya Kumar DK, Navalpur Shanmugam NK, Rodriguez AS, Mitchell T, Washicosky KJ, et al. Alzheimer’s disease-associated beta-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron. 2018; 99: 56-63 e53. [CrossRef]
- Miller MA. The role of sleep and sleep disorders in the development, diagnosis, and management of neurocognitive disorders. Front Neurol. 2015; 6: 224. [CrossRef]
- Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011; 12: 723. [CrossRef]
- Baldi I, Filleul L, Mohammed-Brahim B, Fabrigoule C, Dartigues J, Schwall S, et al. Neuropsychologic effects of long-term exposure to pesticides: Results from the french phytoner study. Environ Health Perspect. 2001; 109: 839-844. [CrossRef]
- Bredesen DE. Inhalational Alzheimer’s disease: An unrecognized and treatable epidemic. Aging. 2016; 8: 304-313. [CrossRef]
- Jansson ET. Aluminum exposure and Alzheimer’s disease. J Alzheimers Dis. 2001; 3: 541-549. [CrossRef]
- Mirza A, King A, Troakes C, Exley C. Aluminium in brain tissue in familial Alzheimer’s disease. J Trace Elem Med Biol. 2017; 40: 30-36. [CrossRef]
- Elif Inan-Eroglu AA. Is aluminum exposure a risk factor for neurological disorders? J Res Med Sci. 2018; 23: 51. [CrossRef]
- Pigatto PD, Costa A, Guzzi G. Are mercury and Alzheimer’s disease linked? Sci Total Environ. 2018; 613-614: 1579-1580. [CrossRef]
- Walach H, Mutter J, Deth R. Chapter 55 - inorganic mercury and Alzheimer’s disease—results of a review and a molecular mechanism. In: Martin CR, Preedy VR, editors. Diet and nutrition in dementia and cognitive decline. San Diego: Academic Press; 2015. p. 593-601. [CrossRef]
- Botchway BOA, Moore MK, Akinleye FO, Iyer IC, Fang M. Nutrition: Review on the possible treatment for Alzheimer’s disease. J Alzheimers Dis. 2018; 61: 867-883. [CrossRef]
- Pistollato F, Iglesias RC, Ruiz R, Aparicio S, Crespo J, Lopez LD, et al. Nutritional patterns associated with the maintenance of neurocognitive functions and the risk of dementia and Alzheimer’s disease: A focus on human studies. Pharmacol Res. 2018; 131: 32-43. [CrossRef]
- Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol. 2006; 59: 912-921. [CrossRef]
- Nowson CA, Service C, Appleton J, Grieger JA. The impact of dietary factors on indices of chronic disease in older people: A systematic review. J Nutr Health Aging. 2018; 22: 282-296. [CrossRef]
- Bhatti AB, Usman M, Ali F, Satti SA. Vitamin supplementation as an adjuvant treatment for Alzheimer’s disease. J Clin Diagn Res. 2016; 10: OE07-OE11. [CrossRef]
- McCaddon A. Homocysteine and cognitive impairment; a case series in a general practice setting. Nutr J. 2006; 5: 6. [CrossRef]
- Barbagallo M, Belvedere M, Sprini D, Dominguez LJ. Chapter 54 - magnesium and Alzheimer’s disease: Implications for diet and nutrition. In: Martin CR, Preedy VR, editors. Diet and nutrition in dementia and cognitive decline. San Diego: Academic Press; 2015. p. 585-592. [CrossRef]
- Roberts RO, Roberts LA, Geda YE, Cha RH, Pankratz VS, O'Connor HM, et al. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. J Alzheimers Dis. 2012; 32: 329-339. [CrossRef]
- Dehghan M, Mente A, Zhang X, Swaminathan S, Li W, Mohan V, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (pure): A prospective cohort study. Lancet. 2017; 390: 2050-2062. [CrossRef]
- Seneff S, Wainwright G, Mascitelli L. Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet. Eur J Intern Med. 2011; 22: 134-140. [CrossRef]
- Broom GM, Shaw IC, Rucklidge JJ. The ketogenic diet as a potential treatment and prevention strategy for Alzheimer’s disease. Nutrition. 2019; 60: 118-121. [CrossRef]
- Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement (N Y). 2017; 4: 28-36. [CrossRef]
- Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011; 86: 876-884. [CrossRef]
- Iyalomhe O, Chen Y, Allard J, Ntekim O, Johnson S, Bond V, et al. A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes. Exp Gerontol. 2015; 69: 159-169. [CrossRef]
- Muller S, Preische O, Sohrabi HR, Graber S, Jucker M, Ringman JM, et al. Relationship between physical activity, cognition, and alzheimer pathology in autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2018; 14: 1427-1437. [CrossRef]
- Sohal RS, Forster MJ. Caloric restriction and the aging process: A critique. Free Radic Biol Med. 2014; 73: 366-382. [CrossRef]
- Hadem IKH, Majaw T, Kharbuli B, Sharma R. Beneficial effects of dietary restriction in aging brain. J Chem Neuroanat. 2019; 95: 123-133. [CrossRef]
- Ray S, Davidson S. Dementia and cognitive decline evidence review. Evidence Review. Age UK, 2014 October 2014. Report No.
- Case report criteria. In: Bmc medical research methodology: BioMed Central, Springer Nature; 2019 [Available from: https://bmcmedresmethodol.biomedcentral.com/submission-guidelines/preparing-your-manuscript/case-report.
- Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D, et al. The care guidelines: Consensus-based clinical case report guideline development. J Clin Epidemiol. 2014; 67: 46-51. [CrossRef]
- Functional medicine: Institute of Functional Medicine; 2019 [Available from: https://www.ifm.org/.
- Bredesen D. The end of Alzheimer’s. London: Ebury Publishing; 2017.
- PACEC. Adass north west region north west dementia perspectives state of the region report. 2016.
- Risk reduction of cognitive decline and dementia: Who guidelines. World Health Organization, 2019.
- WHO. Global action plan on the public health response to dementia 2017-2025. Geneva: World Health Organization, 2017 Licence: CC BY-NC-SA 3.0 IGO Contract No.: ISBN 978–92–4–151348–7.
- Ashford JW, Schmitt FA. Modeling the time-course of alzheimer dementia. Curr Psychiatry Rep. 2001; 3: 20-28. [CrossRef]
- Rindfleisch JA. Biofield therapies: Energy medicine and primary care. Prim Care. 2010; 37: 165-179. [CrossRef]
- Rubik B, Muehsam D, Hammerschlag R, Jain S. Biofield science and healing: History, terminology, and concepts. Glob Adv Health Med. 2015; 4: 8-14. [CrossRef]
- Mangione L, Swengros D, Anderson JG. Mental health wellness and biofield therapies: An integrative review. Issues Ment Health Nurs. 2017; 38: 930-944. [CrossRef]
- Levin M. The wisdom of the body: Future techniques and approaches to morphogenetic fields in regenerative medicine, developmental biology and cancer. Regen Med. 2011; 6: 667-673. [CrossRef]
- Trivedi MK, Branton A, Trivedi D, Nayak G, Lee AC, Hancharuk A, et al. Evaluation of the impact of biofield energy healing treatment (the trivedi effect®) on the physicochemical, thermal, structural, and behavioral properties of magnesium gluconate. Int J Nutr Food Sci. 2017; 6: 71-82 [CrossRef]
- Jain S, Hammerschlag R, Mills P, Cohen L, Krieger R, Vieten C, et al. Clinical studies of biofield therapies: Summary, methodological challenges, and recommendations. Glob Adv Health Med. 2015; 4: 58-66. [CrossRef]
- Jain S, Mills PJ. Biofield therapies: Helpful or full of hype? A best evidence synthesis. Int J Behav Med. 2010; 17: 1-16. [CrossRef]
- Rao A, Hickman LD, Sibbritt D, Newton PJ. Is energy healing an effective non-pharmacological therapy for improving symptom management of chronic illnesses? A systematic review. Complement Ther Clin Pract. 2016; 25: 26-41. [CrossRef]
- Chalfont G, Simpson J, Shukla Y, Venkateswaran V, Milligan C. Whole systems dementia treatment: An emerging role in the NHS? Morecambe Bay Medical Journal. 2018; 8: 58-61.
- Isaacson RS, Ganzer CA, Hristov H, Hackett K, Caesard E, Cohen R, et al. The clinical practice of risk reduction for Alzheimer’s disease: A precision medicine approach. Alzheimers Dement. 2018; 14: 1663-1673. [CrossRef]
- Atkins L, Francis J, Islam R, O'Connor D, Patey A, Ivers N, et al. A guide to using the theoretical domains framework of behaviour change to investigate implementation problems. Implement Sci. 2017; 12: 77. [CrossRef]