Category Archives: Brain aging

Insight 14 – Computerized Brain Training – Good or Bad?

Brain aging, , , ,

One of the foremost concerns of elderly individuals is the possibility of cognitive decline or worse, dementia.  The awareness of the devastating mental losses wrought by Alzheimer’s Disease and other forms of dementia have created the urgency to find activities to prevent or slow cognitive decline.  One of many such activities is the use of computerized brain training exercises to achieve this goal.  This is the topic of my blog.

Background – Changes in Cognition with Age

Even in the absence of disease, some aspects of brain function such as information processing speed (basically the response speed to a mental stimulus), some types of memory such as encoding and retrieval, executive function (basically global decision making) and reward-based behavior tend to decline with age.  In contrast, functions such as semantic memory (facts/knowledge), most aspects of language, emotional processing, autobiographical memory (about self) and automatic memory processes  (rote memory such as riding a bike) remain unchanged with age but are affected by disease.  See (Insight 6 – More longevity building: Ways to minimize brain aging) for a more in depth discussion of aspects of cognition that change or remain stable and their consequences.

Several approaches to minimize age-associated cognitive decline have already gained convincing clinical support (reviewed in Insight 6 – More longevity building: Ways to minimize brain aging).  They are:  

a) a program of aerobic exercise (Insight 4: Anti-aging benefits of aerobic and stretch exercises)

b) continued engagement in serious mental stimulation

c) mastery of new skills

d) optimizing vision and hearing. 

The data indicate that commitment to these 4 pursuits maintains cognition and slows cognitive decline.  These pursuits work because they physically change the brain’s neural networks for the better.  This is termed neuroplasticity.  Thanks to this mechanism, our nerves and connections are strengthened.

Is it reasonable to engage in computerized brain training to prevent cognitive decline?

Computerized brain training

There are now hundreds of companies worldwide that sell computerized brain training exercises. These exercises are referred to as computerized cognitive training (CCT).  Another name for computerized brain training or CCT is computerized brain games. The idea behind CCT is that hours of repetitive practice on standardized exercises will improve the function of the exercise-targeted brain domain.  For example, cognitive training in processing speed should improve reaction time or cognitive training in memory for encoding and retrieval should produce better recall of a list of items.  This training could possibly translate into more global cognitive function and enhance every day activities called  instrumental activities of daily living, such as handling finances, shopping, meal preparation.  

There are three forms of cognitive intervention: cognitive training, cognitive stimulation, and cognitive rehabilitation (Gates et al., 2019).  Cognitive training serves to prevent cognitive decline.  In contrast, cognitive stimulation and rehabilitation restore reduced cognitive function, and compensate for cognitive impairment, respectively.  This blog will discuss the science of cognitive training only.

The efficacy of computerized brain training is unsettled.

Analysis of Computerized Brain Training

There exist hundreds of clinical trials that studied the merits of computerized brain training.  Many of these trials tested a small  number of participants which reduces confidence in the results.  Additionally, in some trials, control participants were “passive controls” who were not exposed to any type of computerized exercise, also reducing confidence in the results.  Considering these issues, it seemed reasonable to focus on critical reviews of the computerized brain training trials.  A review or summary of a large number of trials is called a systematic review. A statistical analysis of a select number of trials that meet strict criteria is called a meta-analysis.  Both review types provide important information.

Early Findings

One of the earliest reports on CCT was a systematic review by Kueider et al., (2012). The authors reviewed the top 38 studies (out of 115) covering the prior 25 years.  These select studies trained elderly (55 years and older) who were without mild cognitive impairment or dementia.  The training included CCT as well as neuropsychological software and video games.  The authors concluded that there were cognitive benefits regardless of the training venue and that “computerized training is effective”.  Use of CCTs produced higher scores in processing speed, memory, attention and executive function.

Several years later, in contrast, an extensive list of eminent professors of gerontology, psychology, neuroscience, neurology, cognitive sciences and related fields submitted a position paper on computerized cognitive training.  See (https://longevity.stanford.edu)for details.  “The strong consensus of this group is that the scientific literature does not support claims that the use of software-based “brain games” alters neural functioning in ways that improve general cognitive performance in everyday life, or prevent cognitive slowing and brain disease”.   That was in 2014.  Since then, several excellent reviews appeared.

Recent Findings

Efficacy supported by meta-analysis

Bonnechère et al., (2020) published a meta-analysis of clinical trials in which participants practiced with commercially available brain training exercises.  Specifically, the goal was to demonstrate maintenance of cognitive function in people, 60 years and older, without any known cognitive difficulties.  The analysis statistically assessed 16 studies which together totaled 1500 patients. Independent of the participants’ age and time devoted to training, the authors conclude that these commercially available exercises improve memory, executive function and processing speed with the greatest improvement in processing speed.  There was no improvement in attention or visuospatial skills.  

This is an interesting review in that it provides for each analyzed study, the name of the cognitive exercise, the company producing the exercise and examples of the “workings” of the exercise.  Unfortunately, some studies enrolled small numbers of participants with about a 10% or so drop-out rate to boot. Importantly, the relation to global function or instrumental activities of daily living was not studied.

Efficacy unsupported by meta-analysis

With a different view, Gates et al., (2019; 2020) reviewed nearly 8000 clinical trial reports (including quasi clinical trials, published and unpublished trials).  Their criteria accepted only trials of computerized cognitive training that lasted for 12 weeks of more, in individuals, 65 years and older with the goal of improvement in cognition of cognitively healthy elderly.  Eight randomized clinical trials with a total of 1183 participants met these criteria. 

Gates et al., (2019) concluded that outcomes of these trials were in the range of low to very low confidence. In short this means that more research is required before one can confidently conclude that computerized brain training improves cognition of cognitively healthy elderly.  This supports the 2014 conclusion of numerous experts in the field (see above).  Gates et al., (2019) also points out that there are no long term studies on cognitive brain exercises (beyond 12 weeks or so). Additionally, there is a paucity of data on the harmful effects (such as anxiety, frustration) of computerized brain exercises. 

Summary – Computerized brain training needs more research

Today, the development and sales of computerized cognitive training, stimulation and rehabilitation is a multi-billion dollar industry.  Findings of major critical reviews in the field of computerized cognitive training indicate that test scores increase with specific training in multiple brain domains.  Importantly, one gets a higher score with repetitive practice using computerized brain training.  Unfortunately, there is no data at present to confirm that spending hours on computerized brain exercises will translate into a more effective ability to carry out daily cognitive challenges.

Select References

Gates NJ, et al.,  Computerized cognitive training for maintaining cognitive function in

cognitively healthy people in late life.  Cochran Database Syst Rev.  13: 1-94, 2019

Kueider et al., Computerized Cognitive Training with Older Adults: A Systematic Review.  PLoS ONE 7:  2012 e40588

Bonnechère, B et al, The use of commercial computerised cognitive games in older adults: a meta‑analysis. Sci Rep. 2020 Sep 17;10(1):15276

Gates NJ et al., Computerized cognitive training for 12 or more weeks for maintaining cognitive function cognitively healthy in late life (review) Cochrane Database of Systematic Reviews 2020, Issue 2. Art. No.: CD012277.

Insight 7 – Brain Health and Sleep

Brain aging, Individual controls aging, , ,

Brain toxins and their disposal by the brain

One of the most exciting discoveries in the past decade is the identification of a “disposal” system in the brain that clears the brain of unwanted compounds (toxins), produced in the course of everyday living.  This system is termed the glymphatic system.  It shares a large portion of its name with a similar system that resides outside the brain.   This outside system is the immune lymphatic system  that protects us from viral and bacterial infections.

Characteristics of the glymphatics; importance of sleep

Unlike the immune lymphatic system, the glymphatic system resides solely in the brain and functions to clear proteins or parts of proteins that accumulate as byproducts of normal brain metabolism.  The main function of the glymphatics is to clear toxins.  Toxins filtered by the glymphatics in the brain are transported in small vessels down the neck and literally dumped into the immune lymphatic system for recycling or elimination elsewhere.  Thus the glymphatics contribute significantly to brain health and longevity!

Importantly, the glymphatic system only works at night.  It is associated with high frequency brain waves and low levels of norepinephrine, an essential brain regulator, that only occur during sleep.  Results of animal studies show that natural sleep produces the essential changes that facilitate the clearance of toxins, in particular beta amyloid protein, implicated in the development and progression of Alzheimer’s Disease.  Therefore, sleep appears to serve an extremely important function – enhancing the clearance of metabolic waste products.  As summarized by researchers at the Langone Medical Center, New York University “restorative function of sleep may be due to the switching of the brain into a functional state that facilitates the clearance of degradation products of neural activity that accumulate during wakefulness” (Xie, Kang, Xu et al., 2013).

The clearance of toxins by the glymphatic system applies to all neurotoxins.  It is postulated that reduced clearance of neurotoxins may contribute not only to the development of Alzheimer’s Disease but may influence the presence of several other diseases e.g. Parkinson’s Disease, Huntingdon’s Disease, amyotrophic lateral sclerosis and frontotemporal dementia.

Age-associated changes in sleep may retard toxin clearance

Age-associated Sleep Stages

Unfortunately sleep quality decrease with age.  Sleep physiology consists of 4 stages per each sleep cycle and the occurrence of about 8-9 cycles per night.  Different brain activities occur in each stage.  For example, stages 1 and 2 constitute light sleep while stages 3 and 4 comprise deep sleep and are followed by REM (rapid-eye movement) associated with dreaming.  Additionally, there is a period of quiet wakefulness prior to sleep. 

With age, the following changes occur:

(1) the period of quiet wakefulness increases such that it takes longer to fall asleep

(2) the time spent in stages 1 and 2 increases – increasing the number of awakenings referred to as sleep fragmentation

(3) the time spent in deep sleep (stages 3 an 4) decreases and may disappear – resulting in the feeling of “not rested”

These changes may lead to daytime “napping” and possibly progress to insomnia.  Many factors such as medication use, nocturnal urinary frequency, chronic pain, hormonal changes and age-related co-morbidities, exacerbate age-related changes in sleep patterns. 

It is important to know how age-related changes in sleep affect the function of the glymphatics.  Regrettably, this has not been critically studied in the elderly.  It is known that the extreme condition of no sleep, insomnia, shuts down the glymphatics, allowing build-up of neurological toxins. 

How to improve quality of sleep

There is no firm answer on how to improve sleep quality.  Clinical trials, generally small with 40-60 participants, point to two interventions that improve sleep quality in the elderly:  a program of aerobic exercise and cognitive behavior therapy (CBT).  Insight 4 provides sufficient detail for a meaningful program of aerobic exercise.   

CBT is a program that provides instruction on the essentials of sleep. This program includes

1)  sleep compression (slowly reducing the amount of time spent in bed (not sleeping) to obtain the optimal sleep time)

2)  sleep hygiene principles focused on appropriate activities, diet, liquids prior to bed time, daytime physical and social activities, light exposure, sleep environment

3)  need to keep a sleep diary and make revisions as necessary 

The CBT program (above) was used in a 4-week program for elderly attending a Veteran’s Adult Day Health Care program.  The CBT was successful in enhancing sleep quality in elderly individuals compared to controls who received general information but not CBT.  This benefit persisted at follow-up 4 months later (Martin et al., 2017).

Reader comments on this discussion are encouraged.  Experiences that enhance sleep quality are of special interest. 

References

1.  Xie, Kang, Xu et al., Sleep Drives Metabolite Clearance from the Adult Brain Science. 18; 342(6156), 2013.

2.  Martin, Song, Hughes et al., A four-session sleep intervention program improves sleep for older adult  day health care participants:  results of a randomized controlled trial. Sleep 40: 1-12, 2017

3.  Reviews:

Jessen, Munk, Lundgaard, Nedergaard. The Glymphatic System – A Beginner’s Guide.

Neurochem Res. 40: 2583–2599, 2015.

Sun, Wang, Yang et al., Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases. Progress in Neurobiology 163–164 : 118–143, 2018.

Insight 6 – More longevity building: Ways to minimize brain aging

Brain aging, Individual controls aging, , , ,

Loss of memory with age is a widespread concern

any older adults have concluded that the only age change really worth caring about is that which slowly robs them of their ability to think.  Generally, muscle weakness, loss of balance and even loss of independence are often rated as less important than the loss of mental capacity that is defined as dementia.  It is important to know that dementia is not a normal age change but rather a neurodegenerative disease that at present has no cure or well defined cause.  Since aging is the main risk factor for disease and since the environment contributes significantly to the rate of aging , not intervening with known strategies will negatively impact memory as well as overall brain function.  Therefore, for longevity building, it becomes especially critical to know the latest and best information that will help preserve brain function.  This blog reviews the science on this topic and relates proven interventions. 

Numerous tests track aging of the brain

Thinking is complicated and so there exist many tests that measure each unique aspect of mental function.  For example, there are tests to measure verbal memory, visual memory, associative memory, source memory, perspective memory, processing speed, spatial navigation, and the most complex, executive function.  Interestingly and importantly, results of many studies that assessed these various brain functions over extended periods of time (more than 30 years in some studies) showed that some components of brain function have the potential to decline while others are quite stable throughout the lifespan.  Thus brain aging appears to be “selective”.   It then becomes important in longevity building to optimize those activities which have a tendency to deteriorate.

Brain functions that remain constant with age

Brain regions – where thinking occurs

Mental functions that do not change with age include semantic memory, most aspects of language, autobiographical memory, emotional processing, and automatic memory processes. Specifically, semantic memory is the memory of facts and knowledge learned over the lifespan.  This remains stable with age although the speed with which this knowledge is retrieved may be slowed.  Language refers to things such as use of appropriate grammar rules and pronunciation.  These are not forgotten and also remain constant.  Autobiographical memory is an individual’s personal history and it, too, is unwavering with time.  Emotional processing refers to typical emotional responses to problems or difficult situations.  Emotional processing takes many forms e.g. abrupt, calm, thoughtful, anxious etc.  Individual emotional processing modes do  not change with age and for the most part, one’s emotional processing at 90 years will mirror that at 30 years.  Finally, automatic memory processes remain stable over time.  Automatic memory relates to things done with minimal mental input or done by rote or constant repetition e.g. driving a car, riding a bike, making coffee, playing tennis.  They are activities that have become so routine that they seem to be accomplished without thinking.  Instability or loss of automatic memory processes usually signals the presence of neurodegenerative disease.

Brain functions that decline with age; longevity building with proven interventions

Mental functions that weaken with age include a) a slowing of information processing speed, b) a decline in executive function, and c) a decrease in specific memory functions that include encoding and retrieval processes, associative, source finding and prospective retention.  This breaks down into the following: information processing speed refers to the quickness at which one can process and respond to information.  This decrement is highly significant since it is a major reason for accidents, mistakes and even falls.  This means that the mental response to novel situations is slowed and depending on the situation, may result in an unfavorable outcome.  Fortunately, processing speed can be improved with practice (see below).  Executive function encompasses various memory skills and abilities to use information to solve daily problems.  Thus, the age-associated decrease in executive function will impinge on important activities such as shopping, banking/finances, house management, medication oversight and meal preparation.  The decline in specific aspects of memory are not as serious as the reduction of information processing speed and executive function but are frequent complaints of the older adult such as not remembering who told me that or where the information came from (source finding memory) or not remembering the reason for doing something, for example, opening the refrigerator door (encoding and retrieval memory) or working on a project and forgetting about a future task such as to turn the oven on at specific time (prospective retention memory).  Whereas these cognitive activities tend to deteriorate with age, proven interventions of intense learning experiences can significantly reduce their loss.

Longevity building – proven interventions to slow brain aging through brain remodeling

Results of numerous animal studies and now many studies in humans using sophisticated imaging techniques such as an MRI and other scans show that brain aging can be minimized and cognitive function of the older adult can be maximized by

a) a program of aerobic exercise (Insight 4)

b) continued engagement in serious mental stimulation

c) mastery of new skills

d) making sure vision and hearing is the best possible. 

These lifestyle choices improve/maintain the connections between brain cells (neurons) and assure their survival.  The effect on the brain is referred to as brain remodeling or positive neuroplasticity. Thus these specific interventions physically alter or remodel the brain in a favorable way.

1) Longevity building with aerobic exercise

Aerobic exercise yields many benefits.  With regard to cognitive function, aerobic exercise improves blood flow to and throughout the brain, promotes formation of new blood vessels, and  improves brain metabolism, thereby reducing accumulations of neurotoxins, substances that harm or kill nerve cells.  Recently, results of animal studies, now supported by data obtained in man not only in young but also older individuals, show increased formation of nerve cells as well as more nerve connections in specific brain regions (brain remodeling).  This supports earlier studies that show a correlation with fitness and cognitive function such that the higher the fitness level, the better the score on various cognitive tests (mentioned above) and the better the brain activity as recorded by a functional MRI scan (a scan that can localize which part of the brain is doing the thinking).

2) Longevity building with participation in intellectually complex work

There is considerable debate as to whether retirement harms brain function.  Initial findings reported a significant decline in brain activity following retirement.  This implied that loss of work-related brain stimulation was a major factor in brain aging and that the continuation of intellectually complex work after retirement served to prevent this loss.  Continuation with complex intellectual activities remains important but current data point to a high degree of variability regarding brain stability after retirement.  The best studies indicate that decline in brain function is evident following retirement but the onset and rate of this decline is highly variable and depends on many factors, for example, complexity of job, health at retirement, satisfaction with the job, educational level.  What is not disputed is that:  part time work post retirement preserves cognition for a significant period of time, hence continuation of complex intellectual activities remains of importance.  Additionally, several small clinical studies show that engagement in solving of complex abstract problems reduces brain aging.

3) Longevity building with learning a new skill

Skill training is specific training for a specific task.  It includes, for example, learning a new language, learning to play a musical instrument, learning computer skills, learning to crochet, and learning to ski.   Learning a new skill, although relatively easy for an adolescent and young adult,  has generally been considered more challenging for the older adult.  However, skill learning prevents decline in brain function.  This is confirmed by studies using brain scans that show positive brain remodeling in the older adult equal to that of the young adult.  Furthermore, it is now known  that for a) skill mastery and b) long term retention, the older adult benefits from training sessions that are seriously challenging and complicated.  This approach favors the best outcome for the older adult. 

Two important clinical trials (ACTIVE, IMPACT) evaluated the effect of proprietary computer programs to improve memory, reasoning and processing speed with specific practice exercises over a 10 week period.  Both studies yielded positive results such that practice test scores in memory, reasoning and processing speed increased with these programs.   The extent to which these improvements are maintained over time has not been studied as yet but would be important to know.

4)  Longevity building with sensory enhancement

There are a number of age changes that diminish the sight and hearing of the older adult.  In the absence of disease these age changes are correctable but unfortunately, they are frequently ignored.  As a result, eye sight and hearing are compromised.  The denial of hearing loss is especially common.  What is not appreciated is that failure to correct these sensory deficiencies is a big factor promoting cognitive decline.  This is because  these deficits reduce the quality of information that is received.  Referred to as “noisy processing” the brain receives inaccurate or fuzzy information which does nothing to promote learning and intellectual stimulation.  Over the long term, little knowledge is gained, and little thinking is done, with the outcome of accelerating brain aging.  Corrective lenses and hearing aids will add measurably to optimizing brain function.

5)  Adequate sleep

Adequate sleep is an important factor in preserving cognition.  This will be the topic of my next blog which points out the relation between adequate sleep and the newly discovered filtration system in the brain that removes neurotoxins.  This is a potential link between sleep, cognitive decline and neurodegenerative diseases.