In older adults, dementia and osteoporosis often coincide.
Standard theory holds that as brain cells die off, physical activity, appetite and dietary quality fall so that bone is lost too. But it appears to be more complicated than that. A recent Neurology paper indicates that bone mineral loss predates the clinical diagnosis of dementia by up to a decade1, and the authors suggest that bone loss, particularly at the femoral neck, might be an early and robust risk factor for neurodegenerative disease.
But is bone loss really a contributory risk factor, or is it just an association? Is the relationship causative, or are the symptoms of disease in bone and brain merely the result of similarly entropic processes running in parallel (but possibly at different rates) in both tissues?
The authors of the Neurology paper were trawling the Rotterdam Study data base. This prospective cohort study of 15,000 adults, set up in 1990, has already yielded well over 1000 publications. It was primarily designed to study cardiovascular, neurological, ophthalmological and endocrine diseases, but bone health was also in the mixie 2, and this paper1 is the first to study the bone / brain connection in that particular cohort.
The authors considered mechanisms which might link bone and brain disease, and listed an impressive number of possible links. They discussed the negative effects of beta amyloid on bone economics3, 4, the effects of falling levels of bone-derived proteins on bone structure and neuronal viability5 and other highly specific biochemical mediators common to both tissues.
Fascinating stuff, but let’s take a step back and look at what might be the bigger picture.
Osteoporosis is not the only pathology associated with an increased risk of dementia.
Many other chronic conditions from cardiovascular disease, diabetes and lung function impairment to chronic kidney disease, depression, constipation and inflammatory bowel disease (IBD) have been linked to dementia as wellie 6-8.
Did I mention cardiovascular disease? Risk factors for CVD include gout, rheumatoid arthritis, systemic lupus, IBD, depression, Type 2 diabetes, hypertension – the list goes on9. And it is, in my opinion, equally unhelpful, because everything appears to be connected.
As a thought experiment, and without jettisoning the idea of inter-systems negative feed-forward loops altogether, let us consider the possibility that all of these problems might be clinical manifestations of an underlying and common set of drivers.
When you take a wide lens and review the pathogenic aspects of the post-transitional diet and life-style, it is clear that most 21st century humans experience chronic inflammatory stress10, type B malnutritionie 11, dysbiosis12 and glycemic mis-match13. Many or all of these drivers of disease are implicated in each one of the pathologies listed above.
This would explain and justify Hickam’s Dictum14, which describes our current clinical reality; most middle-aged folk now have pre-clinical disease15-19, and almost all elderly people today have multiple clinically evident pathologies20-23. The percentage of elderly people with multiple pathologies is still increasing23 – not least, in the notoriously unhealthy USA – and this trend is likely to continue for at least two reasons.
The first is that Type 2 diabetes appears to be very involved in (and a probable co-driver of) many other degenerative conditions24, and the incidence of metabesity and diabetes has been rising for decades25, 26. The second is the incoming tide of younger people with pre-clinical symptoms of multiple pathologies14-19, who will become clinical statistics in due course.
Given these unhealthy facts, and given that the risk of dementia in the elderly is higher in those with multiple pathologies27, dementia figures can only go up28. In this context, focusing on metabolic, mediator and other individual links between brain and bone (or between brain and kidneys, brain and gut, brain and respiratory tract etc) seems to me to be misplaced.
The pathologies that degrade our different organs overlap, and while there is a hard core of genetically-determined cases, the vast majority are driven by the post-transitional, low-energy, ultra-processed and drug-dependent lifestyle we sophisticated modern folk have learned to love. We were persuaded to leave healthier life-styles behind29-31.
We could continue to drift towards multiple pathology and polypharmacy, but in a time of increasing healthcare rationing32-35 and with more to come (see next week), this does not seem sensible. Pasteurian medicine cannot provide modern populations with safe or cost-effective protection, and reactive health care systems are failing (see next week). Improving your diet and lifestyle is the only practical way to achieve a healthier old age(ie 29-31, 36-41.
For the communally minded, it would be better if we could also stop the food industry from peddling its slow-acting poisons to the unwary and the innocent. Our babies are particularly vulnerable; they are being so damaged in utero and childhood that in the UK, a posterchild for ultra-processed food, mental and even physical stunting is reappearing42-44 after an absence of 150 years44.
Ill health is being etched into our children, in a white-collar crime wave committed by an out-of-control industry and its political enablers.
We should use our brains, bones and hearts and march, not drive45, 46, to our selected representatives and demand they take their dirty hands out of the lobbyists’ pockets. Even as the lights of democracy dim in the West, there may still be a few uncompromised politicians willing to do something positive for their electors.
Next week: When systems fail: the end of reactive healthcare and the death of doctoring Pt 2.
- Xiao T, Ghatan S, Mooldijk SS, Trajanoska K, Oei L, Gomez MM, Ikram MK, Rivadeneira F, Ikram MA. Association of Bone Mineral Density and Dementia: The Rotterdam Study. Neurology. 2023 May 16;100(20):e2125-e2133.
- Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. 2004 Jan;34(1):195-202.
- Xia WF, Jung JU, Shun C, Xiong S, Xiong L, Shi XM, Mei L, Xiong WC. Swedish mutant APP suppresses osteoblast differentiation and causes osteoporotic deficit, which are ameliorated by N-acetyl-L-cysteine. J Bone Miner Res. 2013 Oct;28(10):2122-35.
- Li S, Liu B, Zhang L, Rong L. Amyloid beta peptide is elevated in osteoporotic bone tissues and enhances osteoclast function. Bone. 2014 Apr;61:164-75.
- Yuan J, Meloni BP, Shi T, Bonser A, Papadimitriou JM, Mastaglia FL, Zhang C, Zheng M, Gao J. The Potential Influence of Bone-Derived Modulators on the Progression of Alzheimer’s Disease. J Alzheimers Dis. 2019;69(1):59-70.
- Xu H, Garcia-Ptacek S, Trevisan M, Evans M, Lindholm B, Eriksdotter M, Carrero Pharm JJ. Kidney Function, Kidney Function Decline, and the Risk of Dementia in Older Adults: A Registry-Based Study. Neurology. 2021 May 5;96(24):e2956–65.
- Browne J, Edwards DA, Rhodes KM, Brimicombe DJ, Payne RA. Association of comorbidity and health service usage among patients with dementia in the UK: a population-based study. BMJ Open. 2017 Mar 9;7(3):e012546.
- Liu N, Wang Y, He L, Sun J, Wang X, Li H. Inflammatory bowel disease and risk of dementia: An updated meta-analysis. Front Aging Neurosci. 2022 Oct 5;14:962681. Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE. Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging. JACC Cardiovasc Imaging. 2023 Jul;16(7):905-915.
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