Chapter 1 Conclusion - Prevalence, Symptoms, Diagnosis of AD

Prevalence of Alzheimer’s Disease

The 2002 ADAMS study of dementia in the U.S. estimated that 2.7 million people in the U.S. had Alzheimer’s disease (AD)¹¹ and by the year 2005, 24 million people worldwide had AD⁶⁷.   AD prevalence is the highest in those 80 years of age and older. In 2002 there were 9 million people in the U.S. who are 80 years of age or older¹⁰. Therefore in 2002 approximately one in three people 80 years of age or older had AD.  This means almost everyone over 80 will be impacted by AD as they age.  Those of us who live to 80 and beyond will have at least a 1 in 3 chance of getting AD and, if we don’t get AD, we have at least a 1 in 2 chance of caring for a friend or relative with AD.  

The prevalence of AD is increasing both as the size of the population in the U.S. over age 65 continues to increase and as our exposure to aluminum continues to increase.  Currently the Alzheimer’s Association estimates that 5.3 million people in the U.S. have AD⁴.  By 2025 the number of people 65 and older with AD is estimated to reach 7.1 million and by 2050 this number is projected to be 13.8 million, barring adoption of preventive measures, such as those described in this book, or the development of medical cures. 

Symptoms of Alzheimer’s Disease

The clinical symptoms that characterize AD are:

·         Mitochondrial disease

·         Decreasing Aβ peptides and Aβ oligomers in cerebrospinal fluid

·         Increasing tau in the cerebrospinal fluid

·         Shrinkage of the brain

·         Olfactory dysfunction*

*Olfactory dysfunction or anosmia (i.e. the inability to smell) is among the first signs of AD and Parkinson’s Disease^144,145.  

The behavioral symptoms that are a result of cognitive impairment and characterize AD are⁴:

·         Short term memory loss that disrupts daily life

·         Difficulty in planning and problem solving

·         Difficulty completing familiar tasks

·         Confusion with time and place

·         Confusion with visual and spatial relationships

·         Difficulty with word finding during speaking and writing

·         Increased daytime sleepiness*

·         Changes in mood and personality

·         Withdrawal from work or social activities

·        Decreased or poor judgement

*Sleepiness is measured by timing how long it takes for an individual to fall asleep while laying on a bed in a quite dark room.  The largest difference in sleepiness between non-AD (16min.), mild AD (11min.), and moderate AD (8min.) was observed at 10AM and 12PM¹⁴⁶.  In those with dementia, including AD, sleepiness should not be confused with 5 to 20 second long fainting spells, called syncope, that start abruptly and end with spontaneous recovery^147,148. 

Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that is a terminal illness with an average life expectancy of three to nine years post diagnosis.  The AD process occurs in stages 5 to 20 years before the first symptom of cognitive impairment is observed. The stages of AD are as follows: 

·         The first stage of this process involves aluminum facilitating the formation of small soluble protein fragments from amyloid precursor protein (APP), such as Aβ peptides and Aβ oligomers, and insoluble Aβ plaques between neurons. Aluminum conjugates of Aβ oligomers are much more neurotoxic than any other APP metabolite¹⁶. Aluminum’s epigenetic effect of lowering gene expression for both neprilysin and LDL Receptor LRP1, and increasing gene expression for both BACE1 and APP results in more Aβ peptides and Aβ oligomers, and insoluble Aβ plaques^30,31 . Aluminum chloride with D-galactose has been found to create predementia in a mouse model for AD¹⁰⁴.  The first stage of AD can be detected in humans as decreasing levels of Aβ peptides and Aβ oligomers in the cerebrospinal fluid.  These levels decrease as the peptides and oligomers are formed into insoluble Aβ plaques.  

·         The second stage of this process involves aluminum facilitating tau protein clumping together in tangles (NFTs).  Normally tau protein is used for microtubule assembly and stabilization in neurons. Aluminum’s epigenetic effect of lowering the production of the enzyme PP2A and aluminum’s inhibition of PP2A results in excess phosphoryl groups on tau^{22,99,100,136}. Aluminum also facilitates the formation of NFTs from these over phosphorylated tau proteins^24,25. NFT formation results in the death of neurons that are replaced with “tombstones” or “ghosts” of NFTs. The second stage can be detected as increasing levels of tau in cerebrospinal fluid.

·         The third stage is called mild cognitive impairment (MCI) and it occurs 1 to 4 years prior to a person being diagnosed with AD.  MCI is characterized by poor decision making and difficulty in remembering recent events and other lapses of memory.  These symptoms are due to aluminum causing microtubule loss, dendritic die-back, and cortical atrophy resulting in slow loss of memory¹⁴⁹.  MCI can also be a symptom of metabolic (non-AD) dementia that may be curable (see Appendix II).

·         The fourth stage is called Alzheimer’s disease because it can be diagnosed as a slow loss of cognition with symptoms including difficulties with word recall and disorientation, such as getting lost, mood swings and behavioral issues.  These symptoms are due to substantial neuron damage and loss, called lesions, in areas of the brain related to short term and long term memory and decision making.  The severity of this stage can be gauged by performing either volumetric MRI to measure the shrinkages of the brain due to neurons expiring or FDG-PET that gauges the health of mitochondria in neurons.

If you are like me and have one or more aging parents, you may already have witnessed the slow decline of their short term memory. It is disturbing to realize they may have reached the 3^rd stage of AD without even being aware their brains have the hallmarks of AD.  Also if you are like me you may worry that your own brain is beginning that downward spiral into AD.  Until recently it was only in the 4^th stage that the disease could be diagnosed and called AD.  This late stage diagnosis of AD requires two major symptoms with short term memory loss usually being one of the two symptoms. 

According to the Alzheimer’s Association only 45% of those with AD or their caregivers report being told of an AD diagnosis. In part this is due to the difficulty in making the diagnosis. Until recently examination of brain tissue after death was required for a definitive diagnosis of AD.  The two hallmarks of AD histopathology are:

·         Neurofibrillary tangles (NFTs) inside neurons and “tombstones” or “ghosts” of former neurons in between living neurons.

·         Insoluble Aβ plaques formed from Aβ peptides and oligomers in between living neurons.

See sidebar on “Biochemistry and Neurochemistry of AD” for details on these two hallmarks.

One reason it has been difficult to prove what causes AD is that the symptoms of AD become apparent only in the 3^rd and 4^th stage and a definitive diagnosis of AD has required an autopsy.  A new class of ligands has recently been developed that allows for brain imaging by PET scans of both NFTs¹⁵⁰ and Aβ plaques¹⁵¹. This allows researchers to follow the development of the hallmarks of AD histopathology in living patients.  These tests should facilitate our understanding of how aluminum and possibly other environmental toxins cause AD. These tests should also allow faster testing of drugs under development that will provide palliative relief from the symptoms of AD, if not a cure for AD. 

Conclusion of Alzheimer’s Disease

For the last 50 years, in spite of excellent research, the cause of Alzheimer’s has remained controversial.  It may be years before all the needed research is performed and the controversy ends. But now a tipping point has been reached and as described in this chapter there is convincing evidence that aluminum accumulation in our brains can cause Alzheimer’s disease.  Aluminum absorption in select areas of the human brain can result in the cognitive deterioration and associated cerebral pathology seen in AD as described in the following list:

·         Increased amyloid plaque formation in the brain that is a hallmark of AD

·         Increased phosphorylation of tau protein leading to neurofibrillary tangles (NFTs) that are a hallmark of AD

·         Inhibition of mitochondrial enzymes resulting in mitochondrial disease that is a clinical symptom of AD

·         Lesions in the perforant neuronal pathway resulting in loss of short term memory that is a behavioral symptom of AD

The presence of mixed cerebral pathologies becomes more common in individuals with advancing age. Forty-five percent of those over 90 with dementia had a multiple number of cerebral pathologies⁹⁷. The presence of multiple pathologies is associated with increased likelihood and severity of dementia. AD as a single pathology is present in 28% of those over 90 without dementia and 23% with dementia. When a single additional pathology in addition to AD is present the chance of dementia is four times higher than with just AD pathology. When any three or more of these pathologies is present, the chance of dementia is 95% in those over 90⁹⁷.  In addition to aluminum being a causal factor for AD, it has also been implicated as a casual factor for other cerebral pathologies (see Appendix I, III, and IV). For instance in Chapter 2 aluminum’s role as a causal factor for strokes and white matter disease is discussed. This is not to say that aluminum is the only cause of cerebral pathologies.  There are numerous environmental chemicals and several factors, such as head trauma, that have been implicated in cerebral pathologies (see Appendix I). Future research may find additional chemicals in our environment and additional factors that cause cerebral pathologies.

Since the commercial production of aluminum began, there has been a dramatic increase in AD cases worldwide.  There are cases of accidental and occupational exposure to aluminum that have shown that aluminum can cause both early-onset AD and the hallmarks of AD. 

The Alzheimer’s Association finds that Alzheimer’s disease is grossly misunderstood and underestimated.  When they surveyed people in 12 countries they found: 

 “59 percent of people surveyed incorrectly believe that Alzheimer's disease is a typical part of ageing”.

As a society we have made an incorrect assumption:

                “Because we now live longer, more of us will die of Alzheimer’s disease”   

This assumption is a self-fulfilling prophecy unless action is taken by individuals to lower their exposure to aluminum and society to improve regulations on the amount of aluminum in food, drink, and pharmaceuticals.  By lowering our aluminum ingestion and absorption we may be able to live longer without developing and suffering from AD. 

The people of Malaysia and Singapore have a much lower death rate due to AD than the U.S even though they have a similar life expectancy. Could the people of Malaysia and Singapore be ingesting a dissolved mineral called OSA that increases aluminum excretion by their bodies?  See Chapter 5 for the answers to these questions. In Chapter 4 we will discuss ways to avoid or lower aluminum ingestion and in Chapter 5 we will discuss how to decrease aluminum absorption by your brain after ingesting aluminum.