Cognitive Impairment from Dementia and it’s Prevention

Surupa Chakraborty, Amity University, Kolkata

‘I feel as if I’m losing all my leaves. The branches, and the wind, and the rain. I don’t know what’s happening anymore.’ This is the statement that reminds us of Anthony Hopkins’ accurate portrayal of a dementia patient in “The Father” (2020). And precisely, the movie attempts to put the viewers in the place of someone suffering from the elderly battling brain degeneration disorders or dementia, for which there is no real cure.

Dementia, Not a Normal Part of Aging

Dementia is a global loss of cognitive ability and its incidence is exponentially increasing. It has been a major public health concern in recent years and is among the top worries of most elderly people. It affects about 50 million people globally, and based on the stats, there’ll be over 150 million people with dementia by 2050. In medical terms, dementia is a clinical neurodegenerative syndrome (collection of symptoms that might be overlapping) arising as a result of diseases that damage the different aspects of thinking and sound functioning of the brain. The classification of dementia subtypes and associated neuropathological markers are as followed, however, it is noteworthy that the symptoms may vary from person to person depending on which area of the brain is affected.

Alzheimer’s disease (AD), often mistakenly as dementia itself) is the most common cause of dementia, accounting for about 60-70% of all patients with dementia. The nerve cells are damaged by a buildup of two hallmark proteins viz. β-amyloid plaque deposition and neurofibrillary tangles of another (tau) protein. Initial symptoms like forgetfulness, poor memory, getting lost, and difficulty in learning are common.

The build-up of harmful proteins is also a key factor in other disordersbehind the condition like dementia with Lewy bodies (α-synuclein, Lewy bodies, cerebral amyloid angiopathy) and frontotemporal dementia or FTD (fused in sarcoma inclusions, reactive oxygen species such as nitric oxide, superoxides, etc). The processes involved in dementia with Lewy bodies are reportedly similar to those involved in Parkinson’s disease (PD) such as shaking and slowed movement. In addition, many patients with PD are known to develop dementia in the late or advanced stages of the disease, attributed as Parkinson’s disease dementia (PDD).

Other types include vascular dementia (due to ET dysfunction, atherosclerosis, stroke or brain hemorrhage, ultimately slowing a person’s ability to think, plan and pay attention), mixed dementia, and semantic variant progressive aphasia (formerly called semantic dementia).

A Whole lot of Associations: Impact on Dementia

There are many contributors to dementia viz. environmental factors, health risks, neurological changes, and increased accumulations of toxins in the body. Genetics plays a role, but deeper scientific evidence reveals that in most cases, there’s not a simple gene that codes for dementia. Countless studies have supported the same conclusion: stress negatively impacts the gut-brain relationship, plays an integral role in memory loss and cognitive decline, and further quickens the onset or likelihood of dementia. Precisely, stress is the key to dementia but not the ultimate one.

Scientists at the University College London (UCL) recently reported in a study, first of its kind, a possible correlation between cognitive decline and a condition of high blood sugar. The study based on a dataset of 500,000 people, has uncovered that prediabetic people were associated with a smaller hippocampus with having lesions on the brain (white matter hyperintensities, in short, WMHs) and a 54% higher likelihood to develop vascular dementia, caused by reduced blood flow to the brain. To sharpen the correlations, another large data set of people need to be examined to further devise a clinical trial and seek out what the underlying mechanism(s) may be.

An important Neuroscience based study added a class of ‘over-the-counter’ anticholinergic medications (antidepressants, antiparkinson drugs, antipsychotics, antiepileptic drugs, etc.) to the list of additional factors that increase the risk for dementia. The function of anticholinergic medications is to block the function of acetylcholine (a key neurotransmitter in our brain, aids in healthy cognitive functioning of the nervous system as well as regulates movement, digestion, salivation, urination) and to suppress or inhibit its activity when taken regularly for several occasions, say for our indigestion. This would reduce acetylcholine in our stomach to help with our indigestion as well as reduce its levels in our brain. The new findings in the study highlight that taking a much higher dosage of anticholinergic medication without proper medical advice highly increases the risk for dementia.

Previous studies have shown that people with obstructive sleep apnea (OSA), mostly with the more severe forms, show changes in the brain (memory) function and predominantly impact the hippocampus. Given the evidence that OSA over a prolonged time disrupts sleep affecting the clearance rate for excessive amyloid-beta (Aβ) and tau, thereby weakening the ‘key region’ for AD i.e. the hippocampus, there have been suggestions of further investigations to test this hypothesis underlying the neuropathology of AD in the context of OSA. This has been investigated in a new study by analyzing the post-mortem brains of OSA-affected people, only to reveal that OSA severity indeed is a significant predictor of Aβ plaque burden in the hippocampus and significantlyincreasesthe risk for AD by making the hippocampus more vulnerable.

Is there a guide to keep Dementia at bay?

There’s been an answer lingering around us, albeit not a perfect answer but a pretty good one to dodge the situation or reduce the chances of future dementia. Researchers, over the years, have concluded that stress exacerbates and accelerates the risk of this insidious syndrome or dementia. Many studies and meta-analyses have efficiently used stress measures to predict the likelihood of dementia. But we don’t pay heed and change our lifestyle to keep stress under control because all we’re/we’ve been looking for is a “quick fix”, in the form of a vaccine or a pill maybe.

Given the increasingly strong evidence provided by the scientists at UCL that hyperglycemia or sugary blood, seen in prediabetes and diabetes cases increase the risk of cognitive impairment and dementia, better diet and lifestyle changes can be our ‘Knights in shining armor’ helping us to reverse troublesome high blood sugar and thereby keeping dementia at bay. Furthermore, a specific diet or the MIND diet (abbreviated for Mediterranean-DASH Intervention for Neurodegenerative Delay) that has been scientifically evidenced to reduce oxidative stress and inflammation, two significant hallmarks for neurodegenerative disorders, including dementia, might also prove beneficial in reducing the incidence and progression of neurodegeneration with advancing age.

Scientific evidence is now quite strong suggesting that obstructive sleep apnea particularly affects brain efficiency, disturbs the removal of accumulated toxins in the brain, and the healthy restoration of many of our physiological functions, thereby increasing the risks for dementia. In addition, the researchers found that indeed OSA and/or sleep deprivation weakens and shrinks the hippocampus and leads to an increased accumulation of amyloid or potentially tau proteins, which explains the increased risk for AD in such people. It is therefore worth emphasizing the importance of undisturbed sleep and ways by which we can reduce the heavy toll of OSA on neurodegeneration, as current research suggested that adherence to a healthier lifestyle can curb our risk of dementia by up to 40%.

Repeated mini-strokes in a very small region in the brain, often go unnoticed by many which makes them even more dangerous in increasing the chances of developing dementia directly. Part of the risk of dementia can also be accounted for by environmental factors that cannot be prevented or eradicated completely. Plenty of trials on using vaccines and therapeutic drugs including cholinesterase inhibitors (like donepezil, rivastigmine, and galantamine) and memantine against dementia have been going on that are yet to be declared successful as an effective disorder-modifying therapy. More than 20 compounds are known to have completed phase 3 clinical trials in cohorts of patients at different stages of dementia. Despite significant advances, none has demonstrated any significant efficacy in improving the conditions. Hence, our best bet against dementia is an improved lifestyle. Keeping our brain and heart-healthy and overall improving our life by physical exercises, keeping away stress, mindfulness-based intervention, reminiscence therapy, music therapy, not going over-board with certain medications, etc. can potentially slow down the neurodegenerative process, ameliorate particular domains of cognitive function and therefore stand critical for dementia prevention.

Also read: Plasmodium falciparum Acetyl-CoA Synthetase as a target for Malaria treatment

References:

1. Garfield V., Farmaki A. E., Eastwood S. V., Mathur R., Rentsch C. T., Bhaskaran K., Smeeth L., Chaturvedi N. (2021). HbA1c and brain health across the entire glycaemic spectrum. Diabetes Obes Metab., 23(5), 1140-1149. doi: 10.1111/dom.14321
2. Coupland C. A. C., Hill T., Dening T., Morriss R., Moore M., Hippisley-Cox J. (2019). Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med., 179(8), 1084-1093. doi: 10.1001/jamainternmed.2019.0677
3. Owen J. E., Benediktsdottir B., Cook E., Olafsson I., Gislason T., Robinson S. R. (2021). Alzheimer’s disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea. Sleep, 44(3), zsaa195. doi: 10.1093/sleep/zsaa195
4. Agarwal P., Wang Y., Buchman A. S., Holland T. M., Bennett D. A., Morris M. C. (2018). MIND Diet Associated with Reduced Incidence and Delayed Progression of Parkinsonism in Old Age. J Nutr Health Aging, 22(10), 1211-1215. doi: c10.1007/s12603-018-1094-5
5. Law C. K., Lam F. M., Chung R. C., Pang M. Y. (2020). Physical exercise attenuates cognitive decline and reduces behavioural problems in people with mild cognitive impairment and dementia: a systematic review. J Physiother, 66(1), 9-18. doi: 10.1016/j.jphys.2019.11.014

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