Vascular Dementia – By Edward Senu-Oke MD, ABIM, ABOIM

Alzheimer’s disease was first described in 1906 by Dr. Aloysious Alzheimer, a German Neuropathologist who associated specific neuropathologic findings with stereotyped memory and personality changes.  It is questionable whether Dr. Alzheimer was the first to diagnosed dementia, but what is known is that there have been a number of other types of dementia that have been described since Dr. Alzheimer’s discovery.  In 1976, Alzheimer’s disease was first said to be the most common cause of dementia. There has not been a significant challenge to this belief since then.  The purpose of this discussion is to make the case for Vascular Dementia to be considered as the most common cause of dementia.

There is a term used to refer to experience-based techniques of problem solving, learning, and discovering solutions.  It is heuristics.  The implementation of heuristic deduction is not guaranteed, always optimal or even infallible, but it is the method employed by physician and researchers alike to begin to understand the world around us.  Yes, we do live in a world of evidence-based medical practice and goal-oriented medical care.  However, even in this day and age there are areas of medicine that are mysterious to us as clinically aware individuals.  One such area is dementia.  It is estimated that less than half, maybe even as low as 20%, of individuals with dementia are actually diagnosed according to the World Health Organization (WHO).  As the WHO considers dementia a world health priority that is likely to triple in incidence by 2050, it is important to reevaluate what is known and understood about dementia.

The education and therapeutic management of dementia is an area of medicine that I believe has suffered from the fallacies of heuristic deduction.  It is understandable how this could happen, as dementia is a broad category of disease with almost a dozen subcategories resulting from various etiologies, many of which can only be definitively diagnosed postmortem.  It is also a diagnosis of exclusion that is gleamed from time-consuming family interviews, laboratory testing, and an initial degree of clinical suspicion of cognitive impairment.  Because there are so many confounding variable such as societal notions of cognitive decline with aging, inequitable distribution of research dollars to various subcategories of dementia, unfortunate financial motivations for pharmacologic remedies to various aspects of dementia, and a lack of clarity on the true impact of dementia on a patient’s overall health, wellness, and death; it appears that we as clinical evaluators have a hard time evaluating and treating people with dementia.  My goal in this discussion is to reevaluate the epidemiologic understanding of dementia, pathophysiology, and therapeutic considerations for the disease in the future.

For the purposes of this discussion, I specifically define dementia as the stereotypic manifestation of a cascade of dysfunction within the body that results in an irreversible and progressive disorder of mental processing that is characterized by impaired short-term memory, personality changes, and impaired reasoning.  Symptomatically, dementia is best understood in stages. Unfortunately, there is no single, universally accepted staging guideline. This is likely because there is no clear demarcation from one stage of dementia to the next and the penetrance of each symptom is variable.  Inevitably however, one who has dementia moves along a spectrum from mild to late-stage dementia until death.  Once the diagnosis of dementia can be reasonably assured the consideration of the cause and treatment can begin.  As dementia is the result of a cascade of dysfunction, there is a great deal of overlap in the various causes of dementia.  What is universally common about all types of dementia regardless of cause is that there is a disruption in the signaling within the brain that results in impaired cognitive processing and functioning.

Addressing a point of controversy in the epidemiology of dementia, it is widely reported that Alzheimer’s dementia is the most common type of dementia.  My observational studies of dementia suggest otherwise.   It is unclear how Alzheimer’s dementia came to be believed as the most common cause of dementia given that it can only be diagnosed at autopsy.  I suspect that this is the result of a confluence of misrepresentations, overrepresentations, and a lack of understanding of the disease.  Alzheimer’s dementia has somehow morphed from its original definition in 1906 that coupled stereotyped neurologic and cognitive dysfunction with the presence of amyloid plaques and neurofibrillary tangles to a disease that still has stereotyped neurologic and cognitive dysfunction with possible amyloid plaques and neurofibrillary tangles.  What this now means is that all patients with dementia are presumed to be Alzheimer’s type unless convincing evidence otherwise. I argue that this is a conflation of true Alzheimer’s dementia with the broader definition of dementia which has led to the false belief that Alzheimer’s dementia is the most common type of dementia.  Secondarily, there are billions of research and pharmaceutical dollars put into evaluation and treatment of Alzheimer’s dementia which in turn has increased awareness of this specific type of dementia.

Even the belief that Alzheimer’s dementia is the sixth or seventh most common cause of death is not exactly accurate.  More precisely, all causes of dementia equates to the seventh most common cause of death according to the World Health Organization (WHO) 2015 report of the Top 10 leading causes of Death in the World.  In analyzing the leading causes of death further, when accounting for treatable infectious causes of death, dementia is the third most common cause of death after ischemic cardiovascular disease and stroke disease.

Cardiovascular disease, often referred to as heart disease, actually includes dysfunction or injury to the heart and vasculature whether it is congenital or acquired, the vast majority being acquired.  This includes myocardial infarction, congestive heart failure, aortic aneurysm, arterial dissection, carotid stenosis, and others. The goal of evaluation and management of cardiovascular disease is to mitigate the deleterious effects of this dysfunction and prevent death.  The accepted approach to manage cardiovascular disease is to address the disease states that affect the risk of developing cardiovascular dysfunction.  Common cardiovascular risk factors would include hypertension, hyperlipidemia, diabetes, congestive heart failure, known peripheral vascular disease, known coronary artery disease, arrhythmia, and prior stroke.  Of course there are modifiable risk factors for cardiovascular disease such as tobacco abuse, excessive alcohol consumption, physical inactivity, and poor diet.  Affecting these modifiable risk factors should be paramount as they have been shown to reduce the incidence of the common cardiovascular risk factors.

Prior stroke is an important risk factor for cardiovascular disease; and stroke is the second most common cause of death world-wide. A number of strides have been made with regards to diagnosis and treatment of ischemic strokes.  Because of the great risk that stroke poses to an individual and society overall, aggressive evaluation and treatment has been endorsed as the standard of care for patients who present with concern for ischemic stroke.  According to the WHO, early and aggressive therapy of ischemic stroke has reduced the incidence of stroke disease in developed countries.  What is important to remember is that an ischemic stroke is a disease of vascular compromise by definition.  Therefore, it is inexorably linked to ischemic cardiovascular disease.

Patients who have risk factors for cardiovascular disease and who have stereotyped dysfunction consistent with dementia should be considered for vascular dementia.  The mechanisms that result in vascular dementia are exactly the same as the mechanisms that cause cardiovascular ischemic disease and ischemic stroke, the number one and two cause of death world-wide according to the WHO.  They all center on an interplay between inflammatory mediators, mechanical vessel obstruction, and downstream cell field injury.  Understanding that the common final pathway for each of these disease processes are the same as it results in ischemic change, it would not be too far a leap to conclude that vascular ischemia is likely one of the most, if not the most, common cause of dementia. Supporting these findings are the ever improving radiographic data of brains of patients diagnosed with dementia.  Though ischemic disease alone does not equal dementia, the greater the collection of ischemic brain lesions the greater the likelihood of vascular dementia.  With this understanding and against conventional belief, radiographic imaging is very important to the diagnosis of dementia, in particular vascular dementia.

Pathophysiology of Dementia

The brain, or more broadly neural tissue, is delicate and can not tolerate stress well.  The embryonic development of the brain is through a process known as neurovascular patterning or neuroangiogenesis.  These terms very adequately and specifically express the parallel patterning of the nervous system and the vascular system.  They are clearly connected; however, the nervous system is wholly dependent on the vascular system.  Keep in mind that the nervous system is a high energy system energized by glucose and oxygen supplied by the vascular system.  Neuronal cell injury is repaired at least in part and immediately by intracellular mediators but must be supported by nutrients supplied via the vascular system.  This too is represented by the term neuroangiogenesis.

As one ages, neuroangiogenesis tends to decline.  There are a number of factors that reduce the rate of neuroangiogenesis.  Broadly speaking, this decline in neuroangiogenesis includes vascular ischemic changes, nutritional deficiencies, and unchecked inflammatory mediators.  By no coincidence, the same issues that affect neuroangiogenesis are the factors that lead to dementia.  In short, dementia, no matter the type, is a result of brain neural tissue decline associated with vascular system decline within the brain.  This is the Neuroangionectrotic Theory of Dementia.  Therapies that support neuroangiogenesis theoretically should retard the development and/or progression of dementia.  The key considerations for therapeutic intervention should address vascular system support and neuronal system support.

In the area of vascular system support, the goals are to maintain good blood flow and adequate blood pressure.  Blood flow is maintained through medications, over-the-counter supplements, foods that either enhance antiplatelet effects or reduce inflammation, and physical activity.  This would include substances such as aspirin, Vitamin E, fish oil, garlic, ginger, green tea, or even exercise.  Physical activity enhances blood pressure by both sympathetic and parasympathetic means improving endothelial vasomodulation and oxygen extraction.  When the blood pressure is too high for too long it compromises the endothelium’s ability to vasomodulate.  This lack of vasomodulation results in wide tidal shifts of blood into and through a vascular system which in turn affects the ability to provide consistent and adequate oxygen to the neuronal system, and thus neuronal compromise.

When it comes to neuronal system support, the goals are to maintain adequate oxygenation and maintain neuronal health.  As one could infer, adequate oxygenation is largely dependent on good vascular system support.  Considering that a lack of oxygen to the neuron rapidly leads to neuronal compromise, then neuronal injury, and subsequently death; then every area in the brain that suffers microvascular ischemic change is actually suffering significant neuronal injury.  Though oxygen is a key determinant in neuronal health, the ability of the neuron to repair itself is also very important.  To nourish the neuron, one must maintain a diet high in antioxidants such as foods or supplements that contain Vitamin E (ideally mixed tocopherols), B Vitamins, glutathione, Coenzyme Q10, and others.  The diet should also include food with a low inflammatory imprint which includes reduced red meat and pork as well as foods that support cell membrane health such as those containing omega 3 oils.

SUMMARY OF VASCULAR DEMENTIA DISCUSSION

The pathophysiologic state that results in dementia is extremely common but woefully underdiagnosed.  Dementia is a disease that is characterized by cognitive decline, personality changes, and behavioral disturbances.  Dementia is insidious in onset, progressive in nature, and ultimately terminal.  Dementia is a diagnosis of exclusion with stereotyped manifestations.  Diagnosis is most dependent on history; however, laboratory and radiographic studies are important for diagnostic differentiation and exclusion.  When it comes to vascular dementia, there is a high commonality in its pathophysiology and the pathophysiology of ischemic heart disease and ischemic stroke.  Therefore, evidence of ischemic disease in a patient with characteristics of dementia should tip one to the diagnosis of vascular dementia.

Because of the close association of brain neural tissue to its vascular supply and the low rate of regeneration of neural tissue, ischemic tolerance of neural tissue is low.   The issue of low ischemic tolerance of neural tissue is the crux of the Neuroangionecrotic Theory of Dementia.  This theory is also in line with the understanding that ischemic disease is the primary factor underpinning dysfunction and death in patients world-wide.  The application of the philosophical and scientific principle of Occum’s Razor would suggest that this simpler and more inclusive theory of dementia would be more likely than currently held conventional epidemiologic beliefs of dementia.  This shift in understanding also bodes strongly for the case that vascular dementia is the most common type of dementia.

Keeping in mind the Neuroangionecrotic theory of dementia, direct therapies to treat dementia must support the neurovascular system.  The first therapeutic goal is to begin direct therapy as soon as possible to slow progression of disease.  This includes nonpharmacologic and pharmacologic therapies.  Early and aggressive therapy of ischemic stroke has already shown a reduction of incidence of stroke disease in developed countries according to the WHO.  Given the high correlation between vascular dementia and ischemic disease, a similar drop in incidence could be expected with dementia.  Any change in incidence of dementia however would be difficult to analyze at this time secondary to the fact that dementia is so woefully underdiagnosed.  Having a greater and more pragmatic understanding of dementia is what is needed to improve management of this devastating disease.