By Dr. Duane Graveline, M.D., M.P.H.
Nowhere are conflicting scientific views better illustrated than in a literature review on the subject of etiology (causation) of Alzheimer's Disease (AD).
There is debate within the AD research community as to what develops first in AD, amyloid plaques or neurofibrillary tangles. Many scientists in the field of Alzheimer's research believe that this disease is purely genetic in origin. Others believe that amyloid buildup causes a state of chronic inflammation.
In addition there is debate that the blood-brain barrier may be abnormal in persons with AD. To this mix has recently come a compelling new theory that cholesterol lack may be the primary etiologic factor.
A book, 'Alzheimer's Solved' by Henry Lorin, is a must read for every student of this subject. Lorin states that in the majority of cases, Alzheimer's disease is caused by long-term shortages of cholesterol in the elderly brain. He finds only two exceptions to this rule: Down syndrome and those with a history of brain injury or surgery.
His interest in the subject of the relationship began over ten years ago with his observation of the very low incidence of Alzheimer's disease in those people with type-2 diabetes. He noted that as a general rule this form of diabetes is associated with obesity and high blood cholesterol levels.
He found that Cree Indians, with their genetically predisposed diabetes of this type and high cholesterol levels, have very low likelihood of Alzheimer's disease. He wondered could a high blood level of cholesterol offer some protective effect against the development of Alzheimer's disease? He lists an impressive 2500 references in his decade of study.
Lorin's book carries the reader from cholesterol's role in brain structure and function to the process of subtle semi-starvation in the elderly with secondary low serum cholesterol levels and elevated cortisol levels reflecting low-grade stress. From this he takes the reader to a compelling case for amyloid deposition as a substitute for insufficient cholesterol, neuronal degeneration, brain shrinkage and the progressive evolution of Alzheimer's disease.
It is a fascinating read based on known observations, for most cases of this dreaded disease are malnourished with low serum cholesterol and high serum cortisols.
The body is under stress. Cholesterol manufacture and replacement is compromised. Amyloid is Mother Nature's band-aid according to this author, a poor substitute for cholesterol in the lay-down of myelin and in synaptic formation and function, leading to impaired neuronal function and death.
I have reported before on the cognitive impairment that those with naturally low cholesterol and statin users are more likely to experience. These complaints range from transient global amnesia, to aggravation of pre-existing senility to forgetfulness, disorientation and confusion. The mechanism of this side effect of statins is clearly rooted in the biosynthesis of cholesterol and likely is relevant to Lorin's observations about the predisposition to Alzheimer's disease of those with low serum cholesterol.
Only in the past several years have we learned the importance of cholesterol in brain function. Cholesterol has now been proven to be absolutely vital in the formation and function of the trillions of synapses in our brains. Now Lorin suggests that diminished bio-availability of cholesterol may be the key to Alzheimer's disease.
On 9 November 2001, Dr. Frank Pfrieger (and others) of the Max Planck Society for the Advancement of Science announced to the world the discovery that adequate cholesterol bioavailability was the key to both the formation and function of the billions of synapses in our brain supporting neuronal transmission. (1) In the absence of sufficient cholesterol for synaptic support, neuronal transmission fails.
The so-called glial cells of the brain, long suspected of providing certain housekeeping functions, were shown to produce their own supply of cholesterol for the specific purpose of providing nerve cells with this vital synaptic component. Since the brain cannot tap the cholesterol supply in the blood because the lipoproteins that mediate the transport of cholesterol are too large to pass the blood-brain barrier, the brain must depend upon its own cholesterol synthesis, which the glial cells provide.
The highly lipophilic statin drugs such as Lipitor®, Mevacor® and Zocor® far more easily cross the blood-brain barrier and interfere with glial cell synthesis of cholesterol than their hydrophilic counterparts such as Pravachol®.
The results of studies to see whether statins have any benefit for Alzheimer's have been mixed. How, one asks, can statin drugs possibly be of help to those with Alzheimer's disease? The answer no doubt lies in the fact that inflammation is part of the Alzheimer's disease process and statins are effective anti-inflammatory agents. The cholesterol inhibiting effects of statins, which according to Lorin should aggravate Alzheimer's disease may be offset, at least in part, by the anti-inflammatory benefit of these same drugs.
In a study published in 2005, Thomas D. Rea, M.D., M.P.H., of the University of Washington, Seattle and his colleagues studied 2,798 participants 65 years or older in a Cardiovascular Health Study by first establishing their dementia free status by baseline magnetic resonance imaging (MRI) and standardized mental testing. (2)
At follow-up, years later, there were 480 cases of dementia in this group, including 245 attributable to Alzheimer's disease alone. The researchers found that patients using statins had no reduction in their risk of developing dementia from any cause (Alzheimer's disease, mixed Alzheimer's disease and vascular dementia or vascular dementia alone) compared with those who had never used statins. "In this investigation, statin therapy was not associated with a lower risk of dementia," the authors concluded.
A lack of benefit for Alzheimer's with statin use was also the conclusion of another study (Lipitor's Effect in Alzheimer's Dementia - LEADe) (3). Dr. Howard Feldman and others reported that in a study of 640 patients ages 50-90 with mild to moderate AD, using Lipitor 80 mg for 72 weeks did not benefit cognition or global function compared with placebo.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated October 2011