Cognitive decline & reversible dementias
| Educator
11th Nov, 2021Podcast

 

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Transcript

Jacqui Fahey (0:08): Welcome to Common Ground, a podcast series discussing new research and interesting projects in the field of complementary medicine. Hello, my name is Jacqui Fahey, Head of Education at vital.ly.

vital.ly is a digital platform, a professional health resource and a distribution service all in one.

Firstly, I'd like to begin by acknowledging the Gadigal people of the Eora nation as the traditional custodians on the land on which we gather here. I would also like to pay my respect to their elders both past and present.

How our memory is affected as we age has been given considerable attention over recent decades as we often strive to understand the cognitive processes involved. It's not all bad news though. There is a growing body of evidence in both neuroscience and psychological studies showing that the full spectrum of cognitive aging encompasses both gains and losses (1) (2).

For example, the cognitive reserve hypothesis known as CR, specifies that some individuals have a greater ability to withstand clinical changes to the brain. Studies have shown that the protective effect of a higher CR decrease the risk of developing dementia by 48% (2). Contributions to reserve come from a multitude of sources and I shall discuss this in the podcast.

Age associated memory impairment is considered to be a normal part of aging. Interestingly, there are numerous conditions that can cause or mimic the symptoms of dementia and mild cognitive impairment and research has shown a percentage of these conditions are reversible depending on the age of the population under study (3). Some common potentially reversible examples include Vitamin B1 deficiency, B 12 deficiency, thyroid dysfunction, taking certain medications and depression. Vitamin B12 deficiencies account for more than half of the causes of reversible dementias (3), there's more to come on this as well.

Jacqui Fahey (02:16): The Australian population is aging, with older Australian’s accounting for a growing proportion of the total population (4). From the research, there is significant individual variability in age related, cognitive changes.

The normal aging process is associated with declines in certain cognitive abilities, such as processing speed, certain memory, language, visuospatial, and executive functioning abilities, including impaired short-term memory, episodic long-term memory and working memory (2), (5).

Reasons for these changes include structural and functional cerebral alterations.

Functional changes comprise changes in neural activation, functional connectivity, and neurotransmission, while structural changes include grey and white matter deterioration (5).

In essence, gray matter is where the processing is done and white matter is the channels of communication.

Given the broad spectrum of cognitive changes with age, any single process cannot fully explain age-related differences across all individuals (6).

Now here's something fascinating from the research and I touched on the introduction. Certain lifestyle, environmental and health conditions can cause memory loss or other dementia like symptoms that are potentially reversible. Mounting evidence confirms that lifestyle modifications and nutrient approaches may be effective for maximizing cognitive function and quality of life as we age (6).

Before I delve into the potentially reversible causes of memory loss, I'll provide a brief overview of mild cognitive impairment, dementia and explore further cognitive reserve as there are important differences between each of these.

Jacqui Fahey (04:06): So what is mild cognitive impairment, which I shall refer to as MCI. MCI is considered to be an intermediate state between normal cognitive aging and early dementia (7). It's often characterised by objective impairment and cognition that is not severe enough to require help with usual activities of daily living (8). It's often a transitory state caused by reversible conditions (9), (10). The prevalence of MCI in adults age 65 years and older is 10 to 20% with the risk increasing with age and men appear to be at a higher risk than women (9), (10).

Estimates of reversion from MCI to normal condition range from 2.1% to 53%. Not all who experience cognitive decline, especially in advanced stages will develop Alzheimer's disease and some people classified as having MCI will not progress to clinically defined dementia (9), (10).

Currently, there are no accepted pharmacologic treatments for MCI. Research has shown that sustained physical social and cognitive activities can all contribute to postponing or preventing MCI (11).

Now to provide an overview on dementia. Dementia is any decline in cognition that is significant enough to interfere with independent daily functioning. Dementia is characterised as a syndrome rather than a particular disease. The causes of dementia are numerous and include primary neurologic, neuro psychiatric and medical conditions. It is common for multiple diseases to contribute to a patient's dementia syndrome (12). Alzheimers disease is the most common form of dementia in people aged over 65 years. The prevalence of potentially reversible disorders has been reported at 18% in patients under the age of 65 years but only 5% in those over 65.  Although 5% may seem insignificant, correct identification of this condition can help reduce sufferings of the patients and improve their quality of life (3).

 

Jacqui Fahey (06:25): So I touched on earlier about the cognitive reserve hypothesis, as I called CR. CR hypothesis states that some individuals have a greater ability to withstand clinical changes to the brain (2). It is thought that cognitive reserve capacities might explain any non-decline of memory as aging individuals and use alternative or additional paths to ‘remember’. This is fascinating because it's both genetic and environmental factors that contribute to the amount of cognitive reserve.

Genetic factors may influence synaptic density relating to native intellectual ability and environmental factors include education, age culture, and a history of head trauma (13).

While original observations have covered easily measurable variables like education or occupational attainment, more recent studies have delved further into the lifestyle factors, cognitive stimulating behaviors and personality factors. Although most of the research being conducted on CR is centred on cognitive decline and dementia, it is important to realise that CR is not solely related to aging and age-related conditions. For example, prevention of cognitive impairment due to multiple sclerosis, Parkinson's disease and HIV related dementia has been shown to be facilitated by lifelong exposure to CR. It has also been shown to play a role in the recovery from traumatic brain injuries and stroke (14).

 

It's important to note that those with a higher reserve show, more rapid decline once Alzheimer's disease emerges.

Jacqui Fahey (08:12): So what are reversible dementias? These are often conditions that may well be associated with cognitive or behavioural symptoms that can be resolved once the primary cause is treated (3). A vast number of potential causes have been identified that can result in reversible impairment of neurocognitive function in elderly individuals.

Some confusion does exist however, over the term ‘reversible dementia’, as many metabolic causes of dementia have overlap with delirium.

It's important to note cases of so-called ‘treatable dementias’ may be untreatable after a delay in diagnosis. Among all the possible causes of dementias for them to be called reversible, it is that the treatment of the offending agent results in improvement in cognitive functioning (3).

Prevalence is highly variable with a number of studies reporting, a range between 8% and 40%. Though in general, approximately 12% of patients presenting with symptoms of dementia have treatable reversible causes (3).

As I mentioned briefly earlier, many factors affect whether memory loss or other dementia like symptoms are reversible.

They are important to consider and address when assessing cognitive health. Potentially reversible causes of memory loss, dementias, and MCI include (7), (8), (9), (10), (15), (16), (17), (18); certain medications, particularly over long-term use such as your anti-cholinergic drugs. Anti-cholinergic drugs block the action of the neurotransmitter acetylcholine and acetylcholine is involved in transmitting messages that affect muscle contractions in the body and learning and memory in the brain. A recent study found exposure to several types of strong anti-cholinergic drugs is associated with an increased risk of dementia (19).

Another factor is excessive alcohol consumption with vitamin B1 deficiency. This vitamin modulates cognitive performance, especially in the elderly (20).

The earliest and perhaps best example of the interaction between nutrition and dementia is related to B1 deficiency. Known as alcohol related dementia, reduced B1 can drive Alzheimer's disease like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau (21).

B1 is vital for maintaining the blood-brain barrier and interestingly a research group in Vienna has just recently developed a hypothesis whereby iron deposits in the brain resulting from alcohol induced B1 deficiency can be regarded as key factors in cognitive decline. Their hypothesis explores how B1 deficiency, being associated with alcohol use disorders, disrupts the integrity of the blood-brain barrier, allowing for more iron deposits within the brain and this leading to oxidative tissue damage (22). A clinical study is being prepared to explore this further.

Another potential cause of memory loss, cognitive decline and dementia is vitamin B12 deficiency. Many studies have fairly established that a significant number of cases of dementia are reversible following supplementation of vitamin B12 (3). Vitamin B12 (cobalamin) is an essential vitamin for the proper functioning and development of the brain and nerve cells. It plays an important role in the maintenance of the sheaths that cover and protect the nerves of the central and the peripheral nervous system so we experience fast and effective nerve impulse transmission.

Research has shown us, the vitamin B12 delays the onset of signs of dementia provided it is administered in a precise clinical timing window before the onset of the first symptoms (20). B12 can be found in fish, such as sardines, some shellfish, beef, eggs, and dairy.

A few other potential reversible dementias include uncontrolled cardiovascular risk factors and cerebrovascular events such as stroke, anxiety recovery from illness, mood disorders, such as depression, hydration, physical frailty, sleep disorders, such as sleep apnea, social isolation, and hyperthyroidism.

Jacqui Fahey (07:26): So let's now talk about lifestyle modifications and cognitive health. Evidence supports the link between several modifiable risk factors and a reduced risk for cognitive decline and dementia (23). Strong evidence indicates that regular physical activity and management of cardiovascular risk factors reduce the risk of cognitive decline and may reduce the risk of dementia. A healthy diet and lifelong learning and cognitive training may also reduce the risk of cognitive decline (23).

A recent study shows that driving is associated with maintenance of cognitive function and ceasing driving with cognitive decline. Additionally, increasing the amount of time spent driving may also promote the use of maps, which is likely beneficial for improving cognitive function. Specific cognitive activities, such as reading books or newspapers were particularly associated with reversion from MCI to normal cognition (7). Low levels of social activity are considered to predict future functional decline among community dwelling in older persons. Social activities that include human interactions, such as attending meetings and hobbies, or sports are related to MCI reversion (7).

The positive association between educational attainment and level of cognitive function is well established. Higher educational attainment affects cognitive decline but the evidence for this has been mixed. There was a recent meta-analysis and systematic review found education overall is an important factor in aging due to its strong association with level of performance, but the current base of observational evidence is not revealing a consistent and substantial association between educational attainment and changes in cognitive performance in the general population (24).

A recent systematic review and meta-analysis evaluated the efficacy of vitamins without minerals or other co-factors on cognitive function of non-demented people and compared these results by geographical location and the presence of MCI (25). It was found that B vitamin supplementation for three months or longer, maybe beneficial for cognitive function of middle-aged or older people, even when they do not have an apparent B vitamin deficiency.

Long-term intake of antioxidant vitamins could also be beneficial to cognitive function while no observable effect was identified for vitamin D. A review of randomised clinical trials of Gingko biloba extract 120 mg-240 mg daily for up to 12 weeks, found that it may improve some measures of cognitive function such as working and long-term memory, attention-based tasks, speed of information processing executive function, immediate and delayed recall and recognition in healthy adults (26).

Jacqui Fahey (10:36): Long-term supplementation with this herb greater than 24 weeks of 240 mg per day may also be able to improve cognitive function in patients suffering from mild dementia (26).

High adherence to a Mediterranean type diet was also associated with decreased cognitive decline. The findings from recent systematic reviews and meta-analysis suggests that adherence to the Mediterranean type diet and fulfilling the whole diet approach may affect not only the risk of Alzheimer's disease, but also pre-dementia syndromes and their progression towards overt dementia (27).

Numerous studies have demonstrated that physical exercise (PE) prevent cognitive decline linked to aging, reduces the risk of developing dementia, reduces deterioration in executive functions and improves quality of life (28). Findings from a recent meta-analysis found that PE interventions improve cognitive functions in adults older than 50 years, regardless of their baseline cognitive status. Positive benefits occurred with exercise that included Tai-Chi, resistance and aerobic training, that were prescribed either in isolation or combined. Exercise between 45 and 60 minutes of moderate or vigorous intensity and frequency are beneficial to cognitive function (29).

Jacqui Fahey (12:08): So how is PE assisting the improvement of cognitive function? Well it includes the promotion of neurogenesis, and this is the process where new neurons are formed in the brain. It also functions by  angiogenesis. This is where new blood vessels form from pre-existing vessels. Synaptic plasticity, decreasing pro-inflammatory processes and reducing cellular damage due to oxidative stress.

While lifelong participation in PE may be preferable, the adoption of exercise at any age was found in the research to delay or reverse cognitive decline and is considered well worthwhile (29).

So in conclusion it is well established that the impact of aging on cognitive function is complex being influenced by biological and environmental factors (11). More research is warranted on risk reduction prevention and brain health on the effectiveness of specific interventions that address modifiable risk factors (23) and some of these were discussed today. However, what we know from the research to date is very encouraging.

Thanks for tuning into this episode today. We appreciate your support and feel free to leave us a review. We'd love to hear from you. Thank you.

References
1Spreng RN, Turner GR. The Shifting Architecture of Cognition and Brain Function in Older Adulthood. Perspectives on Psychological Science. 2019;14(4):523-542.
2Harada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clin Geriatr Med. 2013;29(4):737-752.
3Chari D, Ali R, Gupta R. Reversible dementia in elderly: Really uncommon?. J Geriatr Ment Health 2015;2:30-7.
4Australian Institute of Health and Welfare. Older Australia at a glance. Cat. no. AGE 87 [Internet]. 2018 [cited 2020 Sep 12]. Available from https://www.aihw.gov.au/reports/older-people/older-australia-at-a-glance
5Toepper M. Dissociating Normal Aging from Alzheimer's Disease: A View from Cognitive Neuroscience. J Alzheimers Dis. 2017;57(2):331-352.
6Park DC, Reuter-Lorenz P. The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol. 2009;60:173-96.
7Shimada H, Doi T, Lee S, Makizako H. Reversible predictors of reversion from mild cognitive impairment to normal cognition: a 4-year longitudinal study. Alzheimers Res Ther. 2019 Dec;11(1):1-9.
8Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014 Dec 17;312(23):2551-61.
9Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014;275(3):214-228.
10Canevelli M, Grande G, Lacorte E, Quarchioni E, Cesari M, Mariani C, Bruno G, Vanacore N. Spontaneous reversion of mild cognitive impairment to normal cognition: a systematic review of literature and meta-analysis. Journal of the American Medical Directors Association. 2016 Oct 1;17(10):943-8.
11Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014;275(3):214-228.
12Gale SA, Acar D, Daffner KR. Dementia. Am J Med. 2018 Oct;131(10):1161-1169.
13D.Y. Hu, E.C. Corum. Nonpharmacological Treatment Approaches. Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders, 2017.
14Yaakov Stern, Daniel Barulli. Geriatric Neurology. Handbook of Clinical Neurology, 2019.
15Evert DL, Oscar-Berman M. Alcohol-related cognitive impairments: An overview of how alcoholism may affect the workings of the brain. Alcohol Health and Research World. 1995;19(2):89.
16Jatoi S, Hafeez A, Riaz SU, Ali A, Ghauri MI, Zehra M. Low Vitamin B12 levels: An underestimated cause of minimal cognitive impairment and dementia. Cureus. 2020 Feb;12(2).
17Allen JL, Klocke C, Morris-Schaffer K, Conrad K, Sobolewski M, Cory-Slechta DA. Cognitive Effects of Air Pollution Exposures and Potential Mechanistic Underpinnings. Curr Environ Health Rep. 2017;4(2):180-191.
18Bethancourt HJ, Kenney WL, Almeida DM, Rosinger AY. Cognitive performance in relation to hydration status and water intake among older adults, NHANES 2011–2014. European journal of nutrition. 2020 Oct;59(7):3133-48.
19Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019;179(8):1084–1093
20Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006 Sep-Oct;10(5):377-85.
21Gibson GE, Hirsch JA, Fonzetti P, Jordan BD, Cirio RT, Elder J. Vitamin B1 (thiamine) and dementia. Ann N Y Acad Sci. 2016 Mar;1367(1):21-30.
22Stephan Listabarth, Daniel König, Benjamin Vyssoki, Simon Hametner. Does thiamine protect the brain from iron overload and alcohol‐related dementia? Alzheimer's & Dementia, 2020
23Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimer's & Dementia. 2015 Jun 1;11(6):718-26.
24Seblova D, Berggren R, Lövdén M. Education and age-related decline in cognitive performance: Systematic review and meta-analysis of longitudinal cohort studies. Ageing Res Rev. 2020 Mar;58:101005.
25Suh SW, Kim HS, Han JH, Bae JB, Oh DJ, Han JW, Kim KW. Efficacy of vitamins on cognitive function of non-demented people: A systematic review and meta-analysis. Nutrients. 2020 Apr;12(4):1168.
26Liu H, Ye M, Guo H. An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer's Patients. Front Pharmacol. 2020;10:1688. Published 2020 Feb 21
27Solfrizzi V, Panza F. Mediterranean diet and cognitive decline. A lesson from the whole-diet approach: what challenges lie ahead?. J Alzheimers Dis. 2014 Jan 1;39(2):283-6.
28Mandolesi L, Polverino A, Montuori S, et al. Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits. Front Psychol. 2018;9:509. Published 2018 Apr 27.
29Northey JM, Cherbuin N, Pumpa KL, et al Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis British Journal of Sports Medicine 2018;52:154-160.