Age-related Cognitive Decline: a Brief Overview and Case History
Introduction
Age-related cognitive decline, and its most clinically extreme form (dementia), are not diseases in themselves.1
Dementia is a word used to describe a group of marked symptoms that occur when brain cells stop working properly. Alzheimer’s disease (AD) is the most common cause of dementia, but there are other types. The next most common forms of dementia are vascular dementia and Lewy body dementia.1
The term dementia describes a group of symptoms that can affect a person’s ability to carry out daily activities without help.1 These include memory problems, confusion and mood changes. A person with dementia will usually experience two or more of these symptoms, such as problems with their memory or getting lost. Someone with mild cognitive impairment may have only one of these symptoms, and unlike dementia it would not normally interfere with their day-to-day life. It is quite possible to have more than one type of dementia at the same time, suggesting a multifactorial treatment strategy is essential for the best outcome.
This multifactorial approach has been promoted by Bredesen for AD, who comprehensively proposes that AD in fact represents six different pathological patterns (or major subtypes), with most people having contributions from more than one subtype:2
- Type 1: Inflammatory (‘hot’), be it infectious (e.g. from viruses) or sterile (e.g. AGE-modified proteins)
- Type 2: Atrophic (‘cold’), the withdrawal of trophic support (e.g. nerve growth factors, oestradiol, testosterone, vitamin D etc)
- Type 1.5: Glycotoxic (‘sweet’, combines 1 and 2) in which advanced glycation end products (AGEs) cause inflammation and insulin resistance leads to withdrawal of trophic signaling
- Type 3: Toxic (‘vile’), a fundamentally different problem, from exposure to toxins, such as heavy metals (e.g. mercury), mycotoxins, aluminium and drugs
- Type 4: Vascular (‘pale’) includes issues such as sleep apnoea and vascular insufficiency
- Type 5: Traumatic (‘dazed’)
Bredesen posits that the major subtypes are 1, 2 and 3. An important practical aspect of this system, and one long recognised by natural therapists, is that the changes and causative factors behind cognitive decline are not just confined to the brain. In other words, dementia is a systemic disease.
Mainstream thinking is focussed on attacking the common pathological findings in AD, being amyloid-beta (Aβ) plaque and tau. But to date, treatments aimed at reducing these have not resulted in beneficial clinical outcomes, and some major pharmaceutical companies have abandoned their search for new drugs to treat dementia.
Other researchers have focussed on one particular novel cause that is outside current mainstream thinking. For example, de la Monte believes that AD is in fact type 3 diabetes (T3D).3 She writes that standard practice in neuropathology is to diagnose AD based on the distribution and abundance of neurofibrillary tangles and Aβ deposits. However, other significant abnormalities include neuroinflammation, gliosis, white matter degeneration, non-Aβ microvascular disease and insulin-related metabolic dysfunction. Her model proposes that deficits in brain insulin and insulin-like growth factor signaling drive pathology and cognitive impairment in AD, meaning it should in fact be regarded as a brain form of diabetes (type 3 diabetes), a new category of insulin resistance disease that can occur independently, or overlap with type 2 diabetes, metabolic syndrome and fatty liver.
Stone and colleagues theorise that AD is in fact largely a microvascular pathology driven by the impact of the constant beating of the heart, especially for the form of dementia that develops much later in life, say at 80 years of age or older.4 In an interview on ABC radio Stone poetically described this phenomenon as follows:
“The beat of our heart is symbolic of life, of energy, of courage and determination. Yet… if we live to old age, the heart destroys us. And it does so in a terrible way, pummelling the brain beat after beat until its small blood vessels burst, and lesions, tens of thousands of them, erode its circuitry, until the brain shrinks around the debris, its function failing. Slowly, relentlessly – this evidence goes - the beat of the heart destroys the memory, the intellect and the personality of the person it had so long served to keep alive.”5
As our arteries stiffen with age (especially the aorta and carotids), this pummelling of the brain is markedly amplified. Indeed, higher levels of aortic stiffness and pressure pulsatility are associated with a greater burden of structural brain damage and lower brain volumes in older adults.6 Among older adults, aortic stiffness and pressure pulsatility are also associated with lower cognitive performance, particularly in the domain of executive functioning/processing speed. This is just one of many studies.
From a completely different angle, Itzhaki has spent almost 30 years exploring the concept that AD is caused by a herpes virus, especially herpes simplex virus type 1 (HSV1).7 She proposes that HSV1 is a major contributory factor for AD, and that it enters the brains of elderly people as their immune system declines with age. It then establishes a latent (dormant) infection, from which it is reactivated by events such as stress, a reduced immune system and brain inflammation induced by infection by other microbes.
Mitochondrial dysfunction as a cause of AD is also receiving increasing attention. There is in fact a large body of evidence supporting the hypothesis that mitochondrial dysfunction plays a central role in AD.8 This dysfunction is not just isolated to neurons. Transmission of AD risk is preferentially found in maternal inheritance, and our mitochondria are inherited from our mothers.
The following case illustrates the principle of approaching dementia and age-related cognitive decline as a disease mosaic dictating a multifactorial strategy.
Case History
Female patient aged 74 years presented with her husband after recently being diagnosed by a neurologist as suffering from AD. Her Mini-Mental State Exam (MMSE) score was 22 out of 30, indicating mild dementia. Blood test results noted triglycerides at 1.1 mmol/L, total cholesterol 6.8 mmol/L, LDL cholesterol 4.6 U/L, T4 14.6 pmol/L, TSH 1.7 mIU/L and vitamin D 63 nmol/L, with nothing else of note from a standard biochemistry panel. She was not taking any conventional medication.
Treatment Plan
My 5-point microcirculation diet was recommended, together with a lower inflammatory diet (somewhat like the Mediterranean diet). A vitamin D3 spray was instituted, and a few months later 30 g of medium chain triglycerides a day.
5-point Microcirculation Diet
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The following were prescribed with the aims of supporting mitochondrial function, lowering neuroinflammation, lowering herpes viruses, providing neuroprotection and improving cognitive function:
A joint formula with boswellia (Boswellia serrata) at 2 tablets per day (for both osteoarthritis and neuroinflammation)
Standardised ginkgo (Ginkgo biloba) tablets (3g of leaf) at 3 twice a day
Ubiquinol at 300 mg per day
Omega-3 1000 mg concentrate capsules at 2 per day
A herbal formula with St John’s Wort (Hypericum perforatum), schisandra (Schisandra chinensis), saffron (Crocus sativus) and skullcap (Scutellaria lateriflora) at 3 tablets a day
A herbal formula with bacopa (Bacopa monnieri), schisandra, siberian ginseng (Eleutherococcus senticosus) and rosemary (Rosmarinus officinalis) essential oil at 4 tablets a day
And three powders mixed together twice a day: N acetylcysteine; a magnesium powder with acetyl-L-carnitine and B vitamins: and another powder with rhodiola (rhodiola rosea), saffron, acetyl-L-carnitine, tyrosine and B vitamins.
Note that because the patient had a good amount of turmeric in her diet, bioavailable curcumin was not prescribed, being reserved as a later option.
Follow-Up
After 6 months this patient was doing well, in large part because her husband has ensured her good compliance with the above regime. On a visit to her neurologist her MMSE score was assessed at 24, and the specialist described her dementia as “arrested”.
Treatment is ongoing, with her situation remaining stable.