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NEUROPSYCHOLOGY UPDATE  - Alzheimer’s
  (2005)

 ALZHEIMER’S DEMENTIA

The Definition and Diagnosis of  Alzheimer's

Alzheimer’s Dementia is a great concern to most persons as they grow older.  Most of us know people who have succumbed to this disease or have people in our family who have had Alzheimer’s.  The definition of Alzheimer’s, according to the Diagnostic and Statistical Manual IV, is as follows: 

There must be evidence of a Memory Loss and there must be evidence of either: Anomia - which is word search, Agnosia - difficulty in recognizing visual objects, Ataxia - motor impairment not due to other known causes, and Executive Function -  losses in ability to plan ahead, etc. 

The diagnosis requires that both the memory loss and the secondary symptom cause significant impairment in daily function. The exact diagnosis of Alzheimer’s depends upon, first of all, clarifying the degree of memory loss and then, secondly, testing for and determining the presence of one of the other four significant symptoms. 

Any tests of these kinds require that you compare the person being tested with other people of his/her own age. The kinds of tests used are very important.  A test for dementia of any kind is only as good as the research studies that have been done on the validity of the tests.  The establishment of test validity is a rather complicated and demanding process and may take a number of years.  In other words, the 20-item questionnaire that you run across in a popular magazines will not give you definitive information on whether or not one has Alzheimer’s. Again, the testing depends upon using tests that are well validated, that are reliable across time for patients, and which have good normative data available for the patient’s age group. 


Risk Factors for Alzheimer's Dementia

 
There are some risk factors for Alzheimer’s, among these, the most prominent is age.  The incidence of Alzheimer’s doubles every five years beginning at 60 years.  In other words, at age 60 the risk of Alzheimer’s is only about 2% by age 65, that is double to 4%, at age 70 to 8%, at age 75 to 16%, at age 80 to 32%, and by age 85 the frequency of Alzheimer’s has gone up to 40% or 50%.  In other words, from being a disease which occurs rarely among persons who are 60 years old, it increases so that by the age of 85 the incidence is almost one half.  In a group of 10 people age 85 or older, 5 of them may have Alzheimer’s.

There are other things which appear to contribute to the risk for Alzheimer’s.  There is the less significant contributions of being of female gender, and/or a history of brain injuries.  One of the things of great concerns to many people are the genetic risk factors.  This is a risk which is present but perhaps not as severe as often believed.   If at least one apoE-4 allele is present the lifetime risk for that person to develop Alzheimer’s is 30%, while the normal risk is 10%.  However, that also means that 70% of persons with the apoE-4 will not develop Alzheimer’s.  The triggers for the expression of the gene are not clear.

Overall, it has been estimated that 3% of Alzheimer’s is related to an autosomal dominant condition.  In the other 97% of cases there does appear to be an increased incidence in family members.  But this is not predictive. It is probably  worthwhile to know if there are members in your family that have had Alzheimer’s, and to be diligent in getting testing for yourself. 

The other very significant symptom of the diagnosis of Alzheimer’s is that the disease has a long and slow onset.  It is not uncommon to see persons with Alzheimer’s, who began having slippage in their memory five or six years before they actually came for neuropsychological testing. 


Other Types of Dementia

 

This long and slow onset is one of the most useful hallmarks of Alzheimer’s.  Other kinds of dementia are not characterized by this pattern.  For example, vascular dementia, related to the occurrence of a CVA or multiple CVAs, often will have a very sudden onset that is correlated with the occurrence of the CVA.  In this case, the person will be someone who has been functioning quite well and suddenly have an episode where they become very confused, disoriented, and may have symptoms such as double vision or difficulty with language, motor weakness, etc. 

In Lewy Body Dementia, the primary symptoms most are motor tremulousness similar to Parkinson’s, visual hallucinations (seeing things that are not there), and shift in attention concentration. Lewy Body Dementia, unfortunately, appears to progress much more rapidly than Alzheimer’s does. 

To simplify, it is certainly the case that all persons, as they grow older, begin to have “senior moments” and forget things.  They may have instances of word search when they cannot remember the name for a “stethoscope” when they are trying to describe their visit to the doctor, or they may forget the names of friends and acquaintances, etc.  The problem becomes to determine whether or not this forgetfulness and word search are beyond what one would expect for their age That is why specific testing is so important. 

Sometimes a diagnosis of “mild cognitive impairment” will be made. The data does not support a diagnosis of Alzheimer’s; repeat testing sometimes shows that Alzheimer’s is detected in later life. This picture of Alzheimer’s is also somewhat confounded by the fact people who are developing Alzheimer’s sometimes become depressed, and their depression may cause them to look more forgetful than they really are.  In some cases, depression may present symptoms that have some resemblance to early signs of dementia.

Neuropsychological testing is still considered one of the best ways to assess Alzheimer’s. Complex brain scans (PET scans) are sometimes used to confirm diagnosis.

 




















NEUROPSYCHOLOGY UPDATE - CELL PHONES AND CANCER:  THE NEED FOR BASIC RESEARCH (2010)

 

New Data:

 Recent data suggests that extended use of cell phones may pose a risk for certain kinds of brain tumors.  According to the World Health Organization, use of cell phones for 30 minutes a day over a period of 10 years may increase the likelihood of gliomas.

 The conclusion was reached on the basis of the review of several studies.  However, it has been commented (Parker-Pope, New York Times, 2011) that the primary study referenced by the WHO depended upon recall of cancer patients regarding their cell phone use over the previous 10 years.  Obviously, this dependence on subjective recall may present problems.  Hopefully, future studies can be done in which exact cell phone use by subjects is noted and recorded.

 Very significantly, recent studies however have demonstrated that brain activity was increased by just 50 minutes exposure to cell phone radiation.  This increased activity was measured by PET (Positron Emission Tomography) scan which measures glucose metabolism.

 

Childhood Exposure:

 Most worrisome are recent reviews indicating that the increased brain activity in response to non-ionizing radiation will penetrate much further in the brains of children because their skulls are smaller and thinner (Dr. Black, a neurosurgeon  at Cedars-Sinai in Los Angeles has commented on this).  Brain scans suggest that the brains of 5-year-olds may be affected two to three times more extensively than those of adults.  Clearly, even the possible risk of childhood leukemia suggests that children’s use of cell phones should be carefully monitored or eliminated.

 

Ionizing Versus Non-ionizing Radiation:

Ionizing radiation is radiation that has enough energy to remove an electron from an atom or molecule.  This includes radiation from x-rays, CT scans, nuclear radiation and so forth.  Non-ionizing radiation does not have enough energy to produce this effect, but it is capable of exciting the molecule.

 Sometimes it has been suggested that because the effects of ionizing radiation on cancer are well-documented and well-known, it is not necessary to even consider the effects of non-ionizing radiation.

 However, this is not the case.  Many studies on non-ionizing radiation which were done 30 to 40 years ago pointed to the possible biological effects of this radiation  (Frey, A., Thomas, J., Gavalas-Medici, R., Adey, W.R., Bawin, S., and Kaczmarek, L.).  The government actively supported this research through DoD, ARPA, ONR, et al.  However, by about 1980, the funding began to slow down and eventually almost came to a halt.  There was a significant lobby against this research from the microwave industry and from the military-industrial complex.  Neither of them wanted to acknowledge even the possibility of non-ionizing effects.  Paul Brodeur summarized much of this in his New Yorker articles in 1989.  This in turn elicited a huge outcry from engineers such as Susskind (Annals of the New York Academy of Science, 1979).  Many engineers and physicists were convinced that biological effects were impossible because a “mechanism” had not yet been found.  Presenting a paper on non-ionizing radiation effects in the 70’s was akin to lighting a match in the trenches during World War II.  The outcry was huge.

 The Russians were also pursuing studies on non-ionizing radiation at that time.  Some of them visited our laboratory at UCLA and seemed convinced that we had found dramatic ELF effects on mind control.  They thought that we were dissembling and hiding these effects from them.  The “zapping” of the American Embassy in Moscow set off another flurry of charges and counter-charges and increased research activity.  Fortunately, to my knowledge, no indications of non‑ionizing radiation exposure were found in the embassy.

 Between the antagonism of some industries and the sometimes comic interchanges with the Russians, it was, at least, an exciting time to be a scientific investigator in this area.

 

Basic Research on Non-Ionizing Radiation:

 Clearly, the question of cancer is important.  However, the basic question of non‑ ionizing radiation effects on brain and behavior is also important.

 Epidemiological studies such as those done on cell phones and brain tumors, are long-term, difficult and broad in their scope, but sometimes are not convincing.  Consequences for other brain-behavioral effects need to be evaluated and studies of basic brain research done.

 As early as 1976, an article was published in Nature (Gavalas-Medici and Day‑ Magdaleno, Volume 261, Number 0557, pages 256 to 259) on the effects of extremely low frequency, weak, non-ionizing electric fields on behavior of monkeys.  A number of research decisions were made to ensure the possibility that effects of these mild fields could be observed.  A subtle measure of behavior (inter-response times) was chosen, along with long exposure (4 hours) and a carefully controlled study balancing “no field” versus “field” conditions over 300 four-hour trials.  The experimental room itself was shielded from ambient fields.

 Because it seemed likely that the effects of the fields would be subtle (voltage levels were 1 to 56 volts, p-p, and frequencies were set at 7-60 Hz), measures of behavior that were known to be sensitive to low doses of drugs along with long exposure times were selected for the study.

 The results of the Nature study indicated that there was a dose-dependent response with stronger fields producing larger behavioral effects for the 7 Hz and 45 Hz conditions, but not for the 60 Hz condition.

 The results for the 7 Hz condition, which is a brainwave frequency, were quite systematic across voltage levels and suggested possible frequency sensitivity to ELF.

 A later experiment at the UCLA laboratory (Adey, R., Bawin, S., and Kaczmarek, L.) pointed out the possible role of calcium efflux across the cell membrane in producing these behavioral effects.

 Behavioral studies that followed the Nature publication sometimes used insensitive measures of behavior (e.g., defecation by mice in an open field).  These studies were more or less doomed to failure (see Medici, R., “Where Has All the Science Gone?” in Steneck, N.H., editor, Risk/Benefit Analysis …, 1982).

 More recently, Anastassiou, et al. (2011) based at Caltech, have published an article on electric field effects in Nature Neuroscience.  In an in vitro study, these investigators were able to use microelectrodes in rat cortical pyramidal neurons that could detect the effect of mini-extracellular electric fields.  These effects were especially evident at low frequencies (8 Hz).  This again, of course, suggests sensitivity at biologically important frequencies.  These fields could modify action potentials even at strengths as low as less than 0.5 μV.  They described these phenomena as ephaptically-mediated changes in brain action potentials caused by the fields “lightly touching” the neurons.

 This research – after an approximately 35-year hiatus- with new measuring techniques suggests that there are many broader questions that need to be answered vis-à-vis non-ionizing radiation.  The fact that these results occur among neurons and may be frequency-sensitive raises questions about a whole new range of possible biological effects.  Hopefully, in the rush to explicate the effects of cell phones on cancer, the basic research itself will not be neglected.

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