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Multiple Ways to Prevent Dementia

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Introduction

Major cognitive loss, generally labeled dementia, increases with age.  Similarly, the fear and anxiety of attaining this state also increases as one ages.  Fortunately, about 40% of dementias are preventable.  The most recent scientific literature identifies 12 modifiable risk factors convincingly associated with the development of cognitive loss.  However, these factors require individual responsibility throughout the life span but undoubtedly are worth the effort as ways to prevent dementia.  These modifiable risk factors are discussed in this blog.

To begin with, there are now many types of dementias.  Thus, effort is underway to group them into a) severe neurological disorders and b) mild neurological disorders.  This has the intended goals of removing the negative connotation of dementia of which the most well known is Alzheimer’s Disease and additionally achieving a more specific diagnosis with tailored treatment for each patient.  Further, a diagnosis of mild neurological disorder may encourage lifestyle choices favorable to prevent progression to severe neurological disorder.

Modifiable Risk Factors:  relative order of highest to lowest risk

Hearing Impairment                               Smoking

Depression                                               Low Social Contact

Traumatic Brain Injury                           Diabetes

Less Education                                         Physical Inactivity

Hypertension                                             Excessive Alcohol Consumption                                

Obesity (BMI>30)                                     Air Pollution

Ways to Prevent Dementia – comments on modifiable risk factors

1.  Hearing Impairment

Hearing loss should be taken seriously as even subclinical loss is related to an increased risk of dementia.  Results of a 25 year study showed that those using hearing aids avoided cognitive decline, possibly because untreated hearing impairment reduces brain stimulation facilitating cognitive decline (see blog 16 Age-related hearing loss inadvertently printed with blog 17).  Therefore, one of the ways to prevent dementia is to correct hearing impairment.

2.  Depression

This condition is associated with an increased risk of dementia.  However, the causal factors are poorly defined and it may, in fact, be an early stage of cognitive decline, rather than depression per se.  Also whether antidepressant drug use is of benefit in preventing dementia has not been established.  Thus, one of the ways to prevent dementia is to evaluate the root cause of depression and with expert help, seek ways to lessen.

3.  Traumatic Brain Injury

Severe traumatic brain injury such as skull fracture, bleeds, edema, falls are highly associated with the development of dementia within several years of injury.  Risk is related to the severity and number of brain injuries. Therefore, ways to prevent dementia are to avoid high impact sports, improve muscle strength to evade falls and treat cardiovascular disease.

4.  Less Education

Because from birth to about twenty years of age, brain growth (new neurons, multiple connections) is optimal, better education during this period yields better protection against cognitive loss in later years.  For older individuals, there are a number of studies supporting a “use it or lose it” approach to cognitive maintenance (see Blog 6 positive neuroplasticity).  This encompasses, for example, such activities as reading, speaking a second language, physical activity, travel and retiring as late as possible.  Computerized training programs have yet to show a significant improvement impact.

5.  Hypertension

Elevated systolic blood pressure (>140 mm Hg) midlife (~ 55 years of age) elevates the risk for dementia.  If hypertension continues into later years, cognitive loss is further increased.  Numerous studies (randomized clinical trials, observational studies) indicate that aggressive lowering of blood pressure (target 120 mm Hg), regardless of the drug class, lowers the risk of dementia.  This is the basis for the American Medical Association’s new hypertension guidelines to lower systolic blood pressure below 130 mm Hg in midlife, regardless of the absence of other risk factors. Thus, one of the ways to prevent dementia is to adhere to the AMA guidelines.

6.  Obesity

A body mass index (BMI) greater than 30 is highly associated with dementia.  This was concluded from 19 longitudinal studies of over five hundred thousand individuals followed for 42 years.  There appears to be a benefit on cognitive function with weight loss in individuals with BMI >25 but the evidence needs additional validation. Thus, it is best to maintain a moderate weight to prevent dementia.

7.  Smoking

Smokers have increased mortality compared to non smokers so that defining the risk for dementia is challenging and considered biased.  However, where there is acceptable data, smoking cessation is beneficial not only on general health but also on reducing the risk of dementia long term.  Therefore, one of the ways to prevent dementia is to stop smoking or better yet, never start.

8.  Low Social Contact

Systemic and meta-analyses of studies world-wide with long term follow-up (>10 years) support factors such as marital status, associations with family and friends, community group activities and paid work as reducing this risk factor.  The effect of this risk factor appears independent of physical health and other lifestyle choices.  Intervention with discussion groups may be helpful but needs further evaluation.

9.  Diabetes

Type II Diabetes carries a risk of dementia related to the duration and severity of the disease.  Unfortunately, it is unknown, at present, which antidiabetic drug is best to prevent cognitive decline. Thus, one of the ways to prevent dementia is to control diabetes with appropriate lifestyle choices and/or medication.

10.  Physical Inactivity

In summation of multiple clinical trials (as in meta-analyses), moderate -vigorous aerobic activity (45-60 minutes for multiple days/week) decreased risk of dementia in cognitively stable individuals and improved cognition in those with mild cognitive impairment.  Also see Blogs 2-5 on exercise.

11.  Excessive Alcohol Intake

It is well established that long term heavy alcohol consumption directly damages the brain and not surprisingly contributes to dementia.  On the other hand, light to moderate drinking lessens dementia risk compared to no drinking (generally long term abstinence).  Moderate drinking is defined as no more than 21 units (one unit equivalent to10 ml or 8 grams pure alcohol/week).  However, debate continues around this as some studies show this cut-off level is too high and should be reduced by as much as 40%. Thus, one of the ways to prevent dementia is to keep alcohol consumption at a low moderate limit.

12.  Air Pollution

This risk factor relies heavily on results of animal studies.  Particulate air pollutants chemically alter the brain with vascular damage, and negative changes in amyloid and tau protein processes.  These changes lead to neurodegeneration.   One review of 13 studies assessing 1-15 years exposure to pollutants found that particulate matter, nitrogen dioxide and carbon monoxide played a significant role in promoting cognitive loss. Although challenging, one of the ways to prevent dementia is to avoid areas of known polluted air.

Ways to Prevent Dementia – Role of Diet

Readers may ask whether diet plays a role in prevention of dementia.  Scientists agree that it is difficult to accurately quantify individual diets.  Nevertheless, epidemiological (observational) studies strongly support the long term adherence to the Mediterranean and the DASH diets (diet high in plant products, nuts, legumes, olive oil and low in saturated fats, meats, salt (see blogs 10 and 11) as associated with reduction in all cause mortality including cardiovascular disease, cancers and Alzheimer’s Disease. 

Although clinical trial results disagree, it is concluded that adherence to the Mediterranean-DASH diet significantly reduces hypertension, diabetes and enhances weight loss.  Thus, it influences three of the above risk factors.  Until the Mediterranean-DASH diet becomes an independent preventive factor in cognitive loss, its influence on defined risk factors for dementia remains important.

Possible Mechanisms

The above risk factors harm the structure and function of the brain.  Structural changes of inflammation, aberrant protein deposits e.g. amyloid/tau proteins, and/or vascular damage occur with untreated diabetes, hypertension, traumatic brain injury, smoking, excessive alcohol consumption, air pollution, obesity, physical inactivity and depression.  Negative functional brain changes such as loss of or lack of maintenance of cognitive reserve are aggravated by poor childhood education, hearing impairment, low social contact as well as depression, physical inactivity and excessive alcohol intake.

Summary – Ways to Prevent Dementia

The risk factors presented in this blog are fortunately modifiable.  This means the responsibility to negate or moderate them falls on the individual.  This supports a view expressed repeated in these blogs – the individual is responsible in large part for his/her own aging.  Genetics gives one the basic components (organ systems, enzymatic processes, interconnections) but it is up to the individual to maintain them with lifestyle choices that optimize them or seek to avoid negative changes. 

If you want to know more about dementia, check out Drug Use In The Older Adult written by myself and Patricia Brown-O’Hara.

References (https://pubmed.ncbi.nlm.nih.gov/)

1.  Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S. et al., Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 2020; 396: 413–46. https://doi.org/10.1016/ S0140-6736(20)30367-6

2.  Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Ratray B.Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis Br J Sports Med . 2018 Feb;52(3):154-160.  doi: 10.1136/bjsports-2016-096587. 

3.  Orgeta V, Mukadam N, Sommerlad A, Livingston G.The Lancet Commission on Dementia Prevention, Intervention, and Care: a call for action. Ir J Psychol Med. 2019 Jun;36(2):85-88. doi: 10.1017/ipm.2018.4.

4.  Jones A, Ali MU, Kenny M, Mayhew A, Mokashi V, He H et al.  Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis. Dement Geriatr Cogn Disord. 2024;53(2):91-106. doi: 10.1159/000536643

5. Rosenau C, Kohler S, Soons LM, Anstey KJ, Brayne C, Brodaty H et al., Umbrella review and Delphi study on modifiable factors for dementia risk reduction.  Alzheimer’s Dement. 2024;20:2223–2239.

6.  Abbasi J.  What to know about the New Blood Pressure Guidelines.  JAMA published online Oct 31, 2025.  doi: 10.1001/jama2025.17664

Osteoarthritis – Robber of Mobility and Independence

Individual controls aging, Osteoarthritis, , , ,

Osteoarthritis is a progressive inflammatory-dependent deterioration of one or more joints (knees, hips, hands, elbow, spine) that robs the older adult of mobility and independence.  “Osteoarthritis is the most com­mon form of arthritis, affecting 1 in 3 people over age 65 and women more so than men” (Hawker, 2019).  After diabetes and dementia, osteoarthritis ranks third in disability prevalence among older adults.

Overview

Osteoarthritis, robber of mobility and independence, begins as an illness characterized by joint pain, joint stiffness (especially when sitting for prolonged periods), muscle weakness, and reduced quality of life.  Over time, structural changes develop in potentially all components of the affected joint.  With permanent damage, osteoarthritis progresses to a disease state that severely limits range of motion, especially walking, leading to a serious disability.  Additionally, it reduces exercise ability, fragments sleep, impairs productivity, encourages early retirement and steals independence.  Sadly, osteoarthritis remains a major disability without an approved disease-modifying therapy.  Symptoms may be minimized with over-the-counter pain/anti-inflammatory medications or injections of steroids into the joint (intra-articular).  Eventually, surgical intervention with total joint replacement is required.

Modifiable Risk Factors

There are two modifiable risk factors strongly associated with osteoarthritis.  They are obesity (adiposity) and joint injury (high impact and/or repetitive mechanical stress).  Additionally, there are several non-modifiable risk factors associated with osteoarthritis.  They include age, gender (female), and genetics (skeletal structure and alignment; uncorrected deformities).

The data suggests that maintenance of a normal body weight and reduction of joint injury, for example, in high stress occupations and elite sports, with proper physical preparations (e.g. exercises to strengthen muscles around joints) would reduce the risk of osteoarthritis.  At present, the actual clinical support for this is minimal because there has been little interest, hence few studies. 

One study on the effect of weight loss and exercise on knee osteoarthritis found that those who adhered to the recommended diet and exercise program had a lower incidence of knee osteoarthritis at 30 months out and those that lost 5% of their body weight has reduced joint injury at 6.5 years compared to controls.  On the effect of exercise alone on the prevention of osteoarthritis, there are  a number of clinical trials, but of poor quality.  It appears that prevention of osteoarthritis by reduction of modifiable risk factors has to date received little clinical attention.

However, it is still important to re-emphasize the wealth of clinical data supporting the multiple benefits of exercise (Insight 2: Skeletal muscles, aging and consequences, Insight 3: Ways to retard skeletal muscle aging, Insight 4: Anti-aging benefits of aerobic and stretch exercises).  For example, an exercise program reduces the risks for numerous other morbidities e.g. cardiovascular disease, and diabetes.  A comorbidity with osteoarthritis accelerates joint deterioration.  Exercise also reduces the risk of weight gain, promotes stable movements and stabilizes joints, thereby reducing mechanical stress.

Pathological Changes

There is growing interest in defining the pathological changes that occur during development of osteoarthritis.  This research effort could potentially give rise to novel and effective disease-altering therapies.

Components of the Joint

The joint brings two bones together. The end of each bone is called the subchondral portion.  It is covered by hyaline cartilage (articular) composed of fibrous proteins such as collagen, lots of water, and a few collagen-secreting cells called chondrocytes.  There is no nerve or blood supply or lymphatic drainage making damage repair difficult.  The synovial membrane that secretes the synovial fluid covers the articular cartilage.  Ligaments (bone to bone) and tendons (muscle to bone) secure the joint.

Identified pathology

1)  Breakdown of cartilage – harmful enzymes slowly destroy collagen and other matrix proteins; the low number of chondrocytes retards repair. 

2)  Inflammation in synovial fluid.  Mechanical injury activates innate and immune responses with production of numerous pro-inflammatory mediators that destroy tissue.

3)  Fibrosis – production of extra matrix proteins that contributes to synovial membrane thickness and stiffness.

4)  Subchondral bone changes – bone supporting joint cartilage remodels in unfavorable ways.

5)  Senescent cells – Chondrocytes senesce and exacerbate the inflammation by production of pro-inflammatory mediators and loss of normal function e.g. collagen repair. (See Blog 23 on senescent cells)

Current Therapies

Osteoarthritic pain is generally treated with topical or oral anti-inflammatory drugs.  Specifically, education, exercise programs (strengthening, cardiovascular, mind-body i.e. Yoga) and weight loss strategies are encouraged. If seriously practiced, this approach consistently reduces joint pain. 

As symptoms worsen, intra-articular injections of steroids provide additional relief.  However, progression to structural damage (radiological confirmation) requires total joint replacement called arthroplasty surgery. The consensus to date is that arthroplasty surgery for the treatment of osteoarthritis is a successful therapy.

Future Therapies

Chemical entities that target one of the five pathological changes mentioned above are in development.  Most, such as the senolytics, are effective in animal models of the disease.  A potential future therapy, pirfenidone, an anti-fibrotic drug, used to treat pulmonary fibrosis, may decrease fibrosis in osteoarthritis.  Another future therapy, now in clinical trials for pain relief in osteoarthritis is the intra-articular injections of a growth factor (portion of FGF-18 termed psrifermin).

Another therapy gaining considerable interest is intra-articular injection or implantation of  stem cells.  The approach is to harvest and inject mesenchymal stem cells (multipotent adult cells obtained from tissues such as bone marrow, fat, umbilical cord). In a critique of clinical trials using stem cell therapy for osteoarthritis, Diego de Carvalho Carneiro et al., (2023) reported findings that “indicate that intra-articular injections of mesenchymal stem cells are efficacious in the treatment of osteoarthritis and the regeneration of cartilage, but that they may be insufficient for the full repair of articular cartilage defects.”  Additional large rigorous clinical trials would be of value.

Conclusions 

Osteoarthritis is a debilitating joint illness/disease that robs an individual of independence.  It desperately needs effective disease-modifying therapy.  Fortunately, potentially valuable therapies are on the horizon.  However, until these therapies are validated, it seems reasonable to establish common sense policies for the prevention of osteoarthritis beginning in childhood and continuing throughout the lifespan.  These policies would include the maintenance of normal body weight throughout life, engagement in proven injury prevention for high impact sports and careers and a continuous exercise program to eliminate the development of co-morbidities and assure normal stresses on all joints.

References (Pubmed)

Aubourg G et al., Genetics of osteoarthritis. Osteoarthritis and Cartilage 30:  636-649, 2022.

Diego de Carvalho Carneiro et al., Clinical Trials with Mesenchymal Stem Cell Therapies for Osteoarthritis: Challenges in the Regeneration of Articular Cartilage. Int. J. Mol. Sci. 2023, 24, 9939.

Hawker GA.  Osteoarthritis is a serious disease.  Clin Exp Rheumatol  37 (Suppl. 120): S3-S6,2019.

Jiang  Y et al., Osteoarthritis year in review 2021: biology Osteoarthritis and Cartilage 30 (2022) 207e215

Katz JN et al., Diagnosis and treatment of hip and knee osteoarthritis: A review JAMA. 2021 February 09; 325(6): 568–578.

Kun E et al., The genetic architecture and evolution of the human skeletal form. Science. 2023 Jul 21;381(6655)

Thoene M et al., The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review. Int. J. Mol. Sci.2023, 24, 8925.

Vincent TL et al., Osteoarthritis pathophysiology – therapeutic target discovery may require a multi-faceted approach. Clin Geriatr Med. 38(2): 193–219, 2022.

Whittaker JL et al., A lifespan approach to osteoarthritis prevention. Osteoarthritis and Cartilage 29 (2021) 1638e1653