4 Speedy Tests for Early Alzheimer’s Detection

Researchers found that simple word-memory tests may accurately detect the earliest stages of Alzheimer's disease and thus improve chances for the prompt treatment of the disease.

Mild cognitive impairment -- subtle but measurable memory problems -- is the earliest clinical stage of Alzheimer's disease and related memory disorders and is typically followed by dementia. People who suffer from mild cognitive impairment have memory problems that are greater than normal for their age but otherwise show no symptoms of dementia.

During this stage, an individual's most complex abilities may be compromised, but activities of daily living, such as traveling, paying bills, and balancing a checkbook, are unaffected.

Spotting Alzheimer's disease at this early stage is important because there is an irreversible loss of function for every month that mild to moderate Alzheimer's disease goes untreated. But detecting mild dementia in its earliest stages is difficult because the person may not show any symptoms, and current methods are often not accurate enough.

Test 1: Animals Names

This is a simple word test that may help in the early diagnosis of Alzheimer’s. It deals with the way in which our brain saves and stores memories. Since some words are learned earlier in childhood and used more frequently in adulthood, certain words will be more difficult for the Alzheimer’s patient to recall.  Word association tests such as this seem to work well in detecting early stage Alzheimer’s.

• First ask the individual to name all the animals they can think of in one minute.

• Then ask her/him to name all the types of fruit they can remember in one minute.

Researchers have found that people with early Alzheimer’s are able to list only 10 to 15 words in contrast to the 20 to 25 words from a healthy individual.

Test 2: Three-word Delayed Recall

• Tell your patient to remember three words.
• Give three common nouns, such as horse, pencil and rose, and ask the patient to repeat them.
• About five minutes later, ask the patient to recall them.
• Individuals without impairment should be able to remember all three words, especially with such prompts as, “The first word was the name of an animal.”
• Remembering only one or two words indicates a need for further evaluation.

Test 3: 20-Questions Test

1. I am going to say 3 words. Please remember them. Those words are: boy, cat, pen. Repeat those words. Later on, I will ask you to recall and repeat them. Here they are again: boy, cat, pen.

2. What is your date of birth?

3. What year is it now?

4. What month is it now?

5. Do you know what day of the week it is now?

6. What is today’s date? (The date should be given within one day of the correct date.)

7. What city or town are you in right now?

8. Where are you right now? (The person must be clearly aware of the place, such as home, hospital, etc.)

9. Do you know the name of the current president or head of the country?

10. Do you know the name of the previous president or head of the country?

11. Repeat each sentence exactly as I say it:
a. Yesterday, I went shopping with my friend.
b. Tomorrow, I will be visiting my daughter.
(Both sentences must be repeated exactly as stated.)

12. Now tell me the three words I asked you to remember. (The person must be able to recall at least two of them.)

13. Has your memory caused you significant problems in the past few weeks?

14. Have family members said to you that you are getting much more forgetful?

15. Have friends or acquaintances said to you that you are getting much more forgetful?

16. If you have six apples and give two apples to David and two apples to Laura, how many apples do you have left?

17. Please count, starting at 7 and adding 7 each time: 7, 14, 21, go on...

18. An orange and an apple are both… (What?) A dog and a bird are both… (What?)

19. Has your memory interfered with your ability to take care of your chores around your house, or your job?

20. What food did you eat for your most recent meal?

Scoring: If the person screened missed five questions or more, it is a good idea to have him or her consult a physician and have some testing done.

Test 4: Counting Coins

• Ask your patient, “If I give you a nickel, a quarter, a dime and a penny, how much money have I given you?”
• When you avoid naming the coins in ascending or descending order of value, this task calls upon comprehension, working (or task completion) memory, planning and calculating skills.
• Inability to arrive at the correct total of 41 cents may indicate a need for further evaluation.

Sources and Additional Information:

http://www.webmd.com/alzheimers/news/20050321/word-test-may-detect-early-alzheimers

http://free-alzheimers-support.com/wordpress/2010/09/a-few-mini-tests-to-do-at-home-for-alzheimers-diagnosis/

http://www.alz.org/professionals_and_researchers_14306.asp

http://www.way-of-the-mind.com/alzheimers-test.html

10 Scoring Approaches for Alzheimer's Clock Draw Test –Alzheimer's Early Detection

Drawing a clock by hand is one of easiest to administer and one of the most popular screening tools that can help to detect mild cognitive impairment, dementia, or Alzheimer's among new patients. The test can be done anytime, anywhere, and can be self-administered as well.

There are numerous versions of the clock-drawing test. They all involve asking the patient to draw the face of a clock. Variations include providing a blank piece of paper or a paper with a pre-drawn (often 10 cm diameter) circle and asking the patient to draw the face of a clock. Further questions from the patients may be politely deferred by repeating the request to draw the face of a clock. Most variations of the test also include asking the patient to draw in the arms to denote certain time. Many times have been used including, 3:00, 3:40, 8:40, 2:45 and so on. They time 11:10 has been suggested as useful because of the distraction of "pull" of the numeral ten on the clock when setting a time. Generally there is no time limit to the test, but the test usually takes only one to two minutes.

If you administer the test to somebody else, in general, look first at symmetry of the numbers of the clock. This can indicate whether or not the patient was able to plan ahead.  Leaving numbers out, repeating numbers, or continuing past the number 12 is also an indication of abnormality. Secondly, look at the hands. Deliberately choose a time from the offered list that is not straightforward because you are looking for disinhibition or “frontal pull.”  The time ‘ten after eleven’ requires that the patient inhibit a reflex to put the hands at the numbers 10 and 11. This also requires abstract thinking to translate the concept of time into a drawing.

Test Description

1. Draw a clock by hand on a large piece of paper (about 10 cm in diameter).
2. Draw the face of a clock and put the numbers in the correct positions.
3. Then draw the hands to indicate 3:40 (time).

Standard Scoring

To score, assign the following points for each part of the drawing:

• 1 point for the clock circle.
• 1 point for all the numbers being in the correct order.
• 1 point for the numbers being in the proper special order.
• 1 point for the two hands of the clock.
• 1 point for the correct time.

Less points you get in the test, more you should worry about the potential symptoms of Alzheimer’s Disease. A normal score is four or five points out of five.

A simple similar results interpretation is offered by Stahelin:

·         The number 12 must appear on top (3 points),

·         There must be 12 numbers present (1 point),

·         There must be two distinguishable hands (1 point),

·         The time must be identified correctly (1 point) for full credit.

A score less than 4 (out of 6) is considered impaired.

Advanced Scoring

While the test itself is very easy and fast to administer or self-administer, and standard scoring process is equally easy and fast to obtain results, there are a number of variations on advanced scoring the clock, more than variations in administering the test itself. Most scoring systems are highly correlated with well-established measures including the MMSE, Dementia Rating Scale and the Global Deterioration Scale. Let’s briefly review the main advanced scoring approaches:

1. Mendez et al. 1992. Clock Drawing Interpretation Scale (CDIS) with the time "ten minutes past eleven." Each positive result earns a score 1.

1.       There is an attempt to indicate a time in any way.

2.       All marks or items can be classified as either part of a closure figure, a hand or a symbol for clock numbers.

3.       There is a totally closed figure without gaps ("the closure figure"). Score only if symbols for clock numbers are present.

4.       A "2" is present and pointed out in some way for the time.

5.       Most symbols are distributed as a circle without major gaps.

6.       Three or more clock quadrants have one or more appropriate numbers per respective quadrant.

7.       Most symbols are ordered in a clockwise fashion.

8.       All symbols are totally within a closure figure.

9.       An "11" is present and is pointed out in some way for time.

10.   All numbers 1 to 12 are present.

11.   There are no repeated or duplicated number symbols.

12.   There are no substitutions for Arabic or Roman numerals.

13.   The numbers do not go beyond the number 12.

14.   All symbols lie about equally adjacent to a closure figure edge.

15.   Seven or more of the same symbol type are ordered sequentially. Score only if one or more hands are present.

16.   All hands radiate from the direction of a closure figure's center.

17.   One hand is visibly longer than another hand.

18.   There are two distinct and separable hands.

19.   All hands are totally within a closure figure.

20.   There is an attempt to indicate a time with one or more hands.

2. Lam et al. 1998. Scoring criteria for clock drawing test. Chose score by description of the produced clock. Lower score you get – smaller signs of Alzheimer’s.

• 0 - Correct time shown with normal spacing.
• 1 - Slight impairment in spacing of lines or numbers.
• 2 - Noticeable impairment in line spacing.
• 3 - Incorrect spacing between numbers with subsequent inappropriate denotation of time.
• 4 - Obvious errors in time denotation (arms misplaced, numbers in wrong place)
• 5 - Abnormal clock-face drawing with inaccurate time denotation (e.g. reversal of numbers, perseveration beyond twelve, misplaced numbers, drawing only to one side, omitting most numbers)
• 6 - Abnormal clock face drawing with inaccurate time denotation (e.g. reversal of numbers, perseveration beyond twelve, misplaced numbers and drawing to one side and omitting most numbers).
• 7 - A recognizable attempt to draw a clock face but no clear denotation of time.
• 8 - Some evidence that a clock face is drawn.
• 9 - Minimal evidence that a clock face is drawn.
• 10 - No reasonable attempt to drawing a clock face (exclude gross visual disturbance, hemiplegia and severe psychotics state).

 

3. Wolf-Klein et al. 1989. Scoring criteria for clock drawing test. Chose score by description of the produced clock. Higher score you get – smaller signs of Alzheimer’s.

·         X - Normal

·         IX - almost normal except for number

·         VIII - almost normal except for spacing

·         VII - very inappropriate spacing

·         VI - perseveration

·         V - absence of numbers

·         IV  - counter clockwise rotation

·         III - other

·         II - irrelevant spatial arrangement

·         I - irrelevant figures

4. Shua-Haim et al. 1996. Simple scoring system. Award one point for each of the following:
   
   
• Approximate drawing of the clock face.
• Presence of numbers in sequence.
• Correct spacial arrangement of numbers
• Presence of clock hands
• Hands showing approximately the correct time
• Hands depicting the exact time

5. Shulman et al. 1986. Classification of clock errors with the time

1.       Visual spatial

a.       Mildly impaired spacing of times

b.      Draws lines outside of circle

c.       Turns page while writing numbers so that some numbers appear upside down

d.      Draws in lines to orient spacing.

2.       Error in denoting time as 3 o'clock

a.       Omits minute hand

b.      Draws single line from 3 to 12

c.       Writes words 3 o'clock

d.      Writes number three again

e.      Circles or underlines 3

f.        Unable to indicate 3 o'clock

3.       Visual spatial

a.       Moderately impaired spacing of lines

b.      Omits number

c.       Perseveration

                                                                     i.            Repeats circle

                                                                   ii.            Continues on past 12 to 13, 14, 15 etc

                                                                  iii.            Counter-clockwise

                                                                 iv.            Dysgraphia

4.       4. Severely disorganized spacing

a.       Confused time, writes in minutes, times of day, months or seasons

b.      Draws picture of human face

c.       Writes words "clock"

5.       Unable to make reasonable attempt at clock

a.       Exclude severe depression or psychotic state.

6. Sunderland et al. 1983. This is one of the most popular scoring systems for evaluating clock drawings. Higher the score – better the patient mental state. This method usually involves giving patients a pre-drawn circle.

·         10-6 - Drawing of clock face with number and circle generally intact

o   10 - Hands in correct position (i.e. Hours hand approaching 3 o'clock)

o   9 - Slight errors in placement of hands.

o   8 - More noticeable errors in placement of hour and minute hands

o   7 - Placement of hands is significantly off course

o   6 - Inappropriate use of clock hands (i.e. use of digital display or circling numbers despite repeated instructions).

·         5-1 -Drawing of clock face with circle and numbers is NOT intact

o   5 - Crowding of numbers at one end of the clock or reversal of numbers. Hands may still be present in some fashion.

o   4 - Further distortion of number sequence. Integrity of clock face is now gone (i.e. numbers missing or placed outside of boundaries of the clock face)

o   3 - Numbers and clock face no longer obviously connected in the clock drawing. Hands are not present.

o   2 - Drawing reveals some evidence of instructions being received but only vague representation of a clock.

o   1 - Either no attempt or an uninterpretable effort is made.

7. SHULMAN scoring system, 1993. Scoring criteria is presented below, while lower score gives higher warnings.

• 0 - No reasonable representation of a clock

—No attempts at all

—No semblance of a clock at all

—Writes a word or name

• 1- Severe level of disorganization as described in 2
• 2 - Moderate visio-spatial disorganization of times such that accurate denotation of 10 after 11 is impossible

—Moderately poor spacing

—Omits numbers

—Perseveration—repeats circle or continues on past 12 to 13, 14, 15 etc.

—Right-left reversal—numbers drawn counterclockwise

—Dysgraphia—unable to write numbers accurately

• 3- Inaccurate representation of 10 after 11 when visio-spatial organization is perfect or shows only minor deviations

—Minute hand points to 10

—Writes ‘10 after 11’

—Unable to make any denotation of time

• 4 - Minor visio-spatial errors

—A mildly impaired spacing of times

—Draws times outside circle

—Turns page while writing numbers so that some numbers appear upside down

—Draws in lines (spokes) to orient spacing

• 5 - Perfect clock

8. Watson Scoring System. The Watson method of scoring the CDT divides the clock into four quadrants.  This technique does not score the hands, but focuses exclusively on the placement of numbers or symbols within each quadrant. 

Scoring is performed through the following approach:

• Draw one line through the center of the circle and the number 12 or mark that best corresponds to the number 12.  Draw another line perpendicular to this line also through the middle of the circle.  This will divide the clock into four segments.
• Moving in a clockwise fashion, count the number of digits in each quadrant beginning with the number 12.  If a digit falls on one of the quadrant lines, it is included in the quadrant preceding the line.  A total of 3 digits in one quadrant is considered correct.
• If there is an error in numbers of digits in the first three quadrants (spanning numbers 12 through 9), assign a score of 1.  For any error in the number of digits in the last quadrant, assign a score of 4.
• The sum of the scores for each quadrant is the total score for the clock.
• Normal range of scores is 0 to 3. Abnormal range of scores is 4 to 7.

If you administer the test on your own and find the results either disconcerting or suspicious, schedule an appointment with your personal care physician. Take the copy of the clock test with you to the doctor appointment, and show the test to the doctor. Insist on a referral to a memory specialist for testing.

There are many diseases that can present as dementia or Alzheimer's. Getting the correct diagnosis is difficult under any and all circumstances. You need to be sure all the proper tests are administered.



Sources and Additional Information:

http://www.alzheimersreadingroom.com/2009/12/alzheimers-clock-draw-test-detect-signs.html

http://www.neurosurvival.ca/ClinicalAssistant/scales/clock_drawing_test.htm

http://www.aging.ufl.edu/files/pdf/tools/clockanalysis.pdf

http://alzheimers.about.com/od/diagnosisissues/a/clock_test.htm

http://www.mumj.org/Issues/v3_i1_march_2006/articles/MUMJ%2016-21%20Clock%20Drawing%20Clinical%20Research.pdf

Using MRI to Predict Alzheimer’s

A new method of brain imaging identifies a pattern of regional brain atrophy in patients with mild cognitive impairment (MCI). The finding indicates a greater likelihood of progression to Alzheimer’s disease.

“Previously, this pattern has been observed only after a diagnosis of probable Alzheimer’s disease,” said the study’s lead author, Linda K. McEvoy, Ph.D, assistant project scientist in the Department of Radiology at the University of California San Diego School of Medicine in La Jolla.

“Our results show that some individuals with MCI have the atrophy pattern characteristic of mild Alzheimer’s disease, and these people are at higher risk of experiencing a faster rate of brain degeneration and a faster decline to dementia than individuals with MCI who do not show that atrophy pattern.”

According to the Alzheimer’s Association, more than five million Americans currently have Alzheimer’s disease. One of the goals of modern neuro-imaging is to help in early and accurate diagnosis, which can be challenging. There is no cure for Alzheimer’s disease, but when it is diagnosed early, drug treatment may help improve or stabilize patient symptoms.

In Alzheimer’s disease, nerve cell death and tissue loss cause areas of the brain to atrophy. Structural MRI allows radiologists to visualize subtle anatomic changes in the brain that signal atrophy. MCI is associated with an increased risk of progression to Alzheimer’s disease.

Rates of progression vary. Some patients progress rapidly, while others remain stable for relatively long periods of time.

For the study, Dr. McEvoy and colleagues set out to determine if they could identify a pattern of regional atrophy characteristic of mild Alzheimer’s disease in order to aid in the prediction of cognitive decline in patients with MCI.

In the study, the researchers analyzed brain MR images from 84 patients with mild Alzheimer’s disease, 175 patients with MCI and 139 healthy controls, using with semi-automated, individually specific quantitative MRI methods. The results showed widespread cortical atrophy in some patients with MCI, involving all cortical areas except those involved with processing of primary motor and sensory information.

However, most indicative of future cognitive decline were atrophy in parts of the medial and lateral temporal lobes and in the frontal lobes. This pattern was also present in the patients with mild Alzheimer’s disease.

“Although these individuals are reporting problems mainly with memory, the atrophy involves more than just memory areas, extending into brain regions involved in planning, organization, problem solving and language,” Dr. McEvoy said.

Followup data were available for 160 patients with MCI. The patients exhibiting atrophy in the brain regions described above showed significant one-year clinical decline and structural brain loss and were more likely to progress to a probable diagnosis of Alzheimer’s disease. MCI patients without that pattern of atrophy remained stable after a year.

Dr. McEvoy hopes that these findings will have an impact on the design of clinical trials to test medications that may slow or halt the progression of Alzheimer’s disease.

“Currently there are no treatments that will prevent or cure Alzheimer’s disease, but information about risk of rapid decline may help patients with MCI and their families plan for the future,” Dr. McEvoy said.

*****

The latest 2009 study confirmed the findings several previous researches, producing similar outcomes. For example, the study of 2003 documents signatures of the early brain changes, occurring several years before the memory problems of early Alzheimer's actually show up.  These changes are caused by loss of brain cells, writes lead researcher Henry Rusinek, PhD, a professor of radiology at New York University School of Medicine in New York City. The researchers say that other studies have pointed to the medial temporal lobe, a small section of the brain, as being very vulnerable to the aging process. These studies show that these changes are also seen in the early stages of Alzheimer's disease. That means mean looking for these brain changes could help pinpoint who is likely to go on to develop Alzheimer's disease in the nearest future.

MRI scans that detect shrinkage in specific regions of the mid-brain attacked by Alzheimer’s disease accurately diagnose the neurodegenerative disease, even before dementia symptoms interfere with daily function, a 2008 study by the Florida Alzheimer’s Disease Research Center (ADRC) in Miami and Tampa found.

“We advocate, based on these findings, that the criteria for the diagnosis of Alzheimer’s disease should include MRI scans,” said the study’s lead author Ranjan Duara, MD, medical director of the Wien Center for Alzheimer’s Disease and Memory Disorders at Mount Sinai Medical Center. “By incorporating MRIs into the assessment of patients with memory problems, early diagnosis can be standardized and done far more accurately.”

“This study demonstrates that MRI brain scans are accurate enough to be clinically useful, both in diagnosing Alzheimer’s disease itself at an early stage and in identifying people at risk of developing Alzheimer’s,” said Florida ADRC Director Huntington Potter, PhD, a neuroscientist at the Byrd Alzheimer’s Center and Research Institute, University of South Florida.

*****

While locating the area of the AD marker place in the brain remains a most significant direction of research, the following analysis can be automated by using the special software.  Massachusetts General Hospital researchers are using automated MRI software to detect individuals in the preclinical phase of Alzheimer's disease with 95% accuracy.

Dr. Rahul Desikan, a researcher at MGH, and colleagues identified which regions of the brain are affected by AD and mild cognitive impairment in two patient groups of 97 and 216, respectively. Based on earlier pathological and imaging studies, the investigators confirmed that those with AD or MCI demonstrate a significant difference in thickness and volume in their entorhinal cortex, hippocampus, and supramarginal gyrus. The researchers then processed MRI scans of individuals with AD and MCI using FreeSurfer, open source software developed at MGH and the University of California, San Diego

Sources and Additional Information:

http://psychcentral.com/news/2009/02/12/mri-predicts-alzheimers/4059.html

http://www.webmd.com/alzheimers/news/20031125/mri-brain-scan-predicts-memory-decline

http://ihealthbulletin.com/blog/2008/12/21/mri-diagnosis-predict-alzheimers-disease/

http://www.psychiatrictimes.com/alzheimer/content/article/113619/1451362

Causes and Risk Factors for Alzheimer's Disease

Alzheimer`s disease (AD) is a neurological disorder which is characterized by progressive neuro-degeneration manifested through functional, behavioral and cognitive abnormalities. It is a form of dementia and it is common for aging people, marking the last decade of the affected patients` life. Over 8 million people around the world are suffering of AD. It is a fact that 10 - 15% of individuals over the age of 65 are affected by cognitive decline, AD being the most frequent disorder.

It is important to identify early risk factors for Alzheimer’s disease because the neuro-degenerative processes of Alzheimer’s disease may begin in midlife.

Identification of these risk factors may shed some light on the patho-physiology of Alzheimer’s disease and also provide new potential avenues for its prevention and treatment. The preliminary findings showing an association between vascular risk factors and Alzheimer’s disease need to be replicated in independent populations, and no population based study has yet evaluated the association of both midlife blood pressure and cholesterol concentrations with Alzheimer’s disease in later life in both sexes.

RISK FACTORS

A number of factors increase the risk of developing Alzheimer`s disease:

• Age: Age is the most dramatic risk factor, so that 50% of the world`s elder population is affected by this disease.
  
• Sex: Estrogen has a benefic role on the brain by protecting it from memory loss and reduced mental functioning. Due to the estrogen loss after menopause, women are more predisposed to this disorder than men.
  
• Family history of dementia: patients who have first degree relatives with AD present a high risk in developing this disease.
  
• Head trauma/injuries.
  
• Education level: individuals with low education have a greater risk of getting AD compared to individuals with a high level of education, who have a higher number of neurons and synapses, which protects the brain from degeneration. The first category of patients develop dementia symptoms earlier and the progression of Alzheimer`s disease is quicker.
  
• Vascular disease: can cause dementia. Strokes can cause AD in elder individuals. Also, the risk factors for vascular disease are common with the ones for AD, such as: high blood pressure, smoking, high cholesterol level, high homocysteine level.
  
• Diabetes: because of the vascular mechanisms or because of the interaction of insulin degrading enzymes with the amyloid metabolism.
  
• Coronary arteries bypass grafting.
  
• Down Syndrome: young mothers who gave birth to children diagnosed with Down Syndrome present a higher risk of developing AD; also the Down Syndrome patients are highly predisposed to this form of dementia because of the neurological changes in the brain.
  
• Genetic factors: a cholesterol-bearing protein - the apolipoprotein e4 (ApoE-4) allele increases the risk of Alzheimer`s disease.
  
• Small head size: some studies show that the shrinking of the brain in elder people can cause mental impairment.
  
• Depression: Untreated depression can lead to dementia and it has been proven that depression itself represents an early symptom for Alzheimer`s.
  
• Blood pressure, cholesterol, and risk of Alzheimer’s disease; High systolic blood pressure in midlife is a significant risk for Alzheimer’s disease in later life. Borderline high systolic blood pressure in midlife also increases the risk; Midlife diastolic blood pressure had no significant effect on the risk of Alzheimer’s disease. High serum cholesterol concentration in midlife is a significant risk for Alzheimer’s disease. Notably, in Japanese-American men the raised diastolic blood pressure in midlife predicted Alzheimer’s disease only in participants never treated with antihypertensive drugs. From this perspective, the potential risk of Alzheimer’s disease related to raised diastolic blood pressure, emphasizes the importance of raised systolic blood pressure, even in people with normal diastolic blood pressure. Blood pressure control may prevent dementia, in patients with isolated systolic hypertension.
  
• High serum total cholesterol concentration in midlife also predicts Alzheimer’s disease in later life. This finding is consistent with the findings in elderly Finnish men. Recent studies extend these findings to younger age groups and both sexes, making these data more representative.
  
• The medical history. Patients with Alzheimer’s disease were more likely to have been treated with antihypertensive drugs in midlife, but at re-examination later in life there was no difference between treated and not treated patients. At reexamination, patients with Alzheimer’s disease were significantly more likely to have a history of myocardial infarction and cerebrovascular symptoms (almost invariably expressed as transient ischemic attack) and less likely to be alcohol users.
  
• Clinical indicators of atherosclerosis are more common in patients with Alzheimer’s disease than subjects without dementia. A population based, cross sectional study has previously indicated an increased risk of Alzheimer’s disease in patients with atherosclerosis. Hypertension and hyper-cholesterolaemia may increase the risk of dementia by inducing atherosclerosis and impairing blood flow, but they may also directly induce the neuro-degeneration of Alzheimer’s disease.
  
• Recent findings are suggesting that hypertension and hyper-cholesterolaemia themselves pose a risk for Alzheimer’s disease. Furthermore, the combination of hypertension and hyper-cholesterolaemia in midlife was a particularly strong predictor of Alzheimers disease; these factors may accelerate the development of Alzheimer’s disease partly through different patho-physiological mechanisms.
  
• Apolipoprotein E genotype may influence the observed associations, but more than 85% of the variation in serum cholesterol concentrations is thought to be independent of the apolipoprotein E genotype. Accordingly, the findings in elderly Finnish men suggested that high serum cholesterol concentration was an independent risk factor for Alzheimer’s disease regardless of the apolipoprotein E genotype. However, more research is needed to determine if apolipoprotein E genotype modulates the effects of risk factors for Alzheimer’s disease.
  
• The observed relation between midlife vascular risk factors and Alzheimer’s disease later in life may have implications for the prevention of dementia as both hypertension and hyper-cholesterolaemia can be treated.

OTHER POTENTIAL RISK FACTORS

• Mental inactivity: without mental exercise, especially in midlife, the brain is inclined to degeneration.
  
• Midlife depression.
  
• Psychological distress.
  
• Exposure to metals especially to aluminum, was once believed to be relevant - renal patients present the phenomenon of ”dialysis dementia” because of the exposure to dialysate with high concentrations of aluminum. They present typical AD pathology. Likewise zinc can induce Abeta aggregation in vitro.

PROTECTIVE FACTORS WHICH DECREASE THE RISK OF DEVELOPING ALZHEIMER`S DISEASE

• Social and cognitively stimulating activities.
  
• Diets high in antioxidants, olive oil, fish.
  
• Nonsteroidal anti-inflammatory drugs (NSAIDs).
  
• Cholesterol-lowering agents.
  
• Vitamin C and E intake may reduce the prevalence of AD.
  
• Alcohol in moderate amounts may be protective.

MILD COGNITIVE IMPAIRMENT


The early detection of functional and cognitive impairment has made it easier to identify very mild manifestations of cognitive decline, which is called “mild cognitive impairment” (MCI). The amnesic MCI shows an increased risk of developing into AD. However, not all MCI cases will be affected by dementia, because mild cognitive impairment occurs also in patients with psychiatric diseases, cerebrovascular diseases, or systemic disorders. The transition from MCI to Alzheimer`s disease is recognized through striking cognitive decline, for example the selective loss of short-term memory.

ALZHEIMER`S DISEASE PREVENTION


Studies have shown that individuals who have hobbies which need high mental resources such as: playing crosswords, board games, cards, chess, people who play a musical instrument and explore their creative side in life, are generally protected from mental lability in their elder years. It has been also concluded that food supplements with vitamins B12, C and E, Gingkobiloba extracts, Acetyl L- Carnitine, Thiamin, Phosphatidylserine prevent brain degeneration.


Authors: Ruxanda Dana Chirileanu, Mihaela Simu, Daniela Reisz, Simona Males, Raluca Tocai, Ramona Albici, Neurology Clinic UMPh Timisoara
Source: Medicine in evolution, Nr. 4/2008

Head Injury - Risk Factor for Alzheimer's Disease

Although more than four decades have passed since British neurosurgeon McDonald Critchley described severe memory problems in a sample of boxers—presumably the result of repeated head trauma—the relationship between brain injury and Alzheimer's disease (AD) has proven difficult to unravel. For years, there was scant evidence that head injuries endured by nonboxers posed an increased risk for AD; although epidemiologic studies linking the two conditions began appearing in the 1980s, negative studies continue to be published with enough frequency to ensure that the issue remains controversial. And while recent reports have revealed neuropathologic changes in some injured brains that bear a remarkable resemblance to AD, the interpretation and implications of these findings remain uncertain.

Multiple researchers have overwhelming data that boxers have a high rate of dementia. Playing other sports where head injuries are common may also increase the risk of developing dementia, or perhaps cause it to develop at an earlier age. In an article published in NeuroSurgery in 2005, University of North Carolina scientists tested more than 2500 retired professional football players. They found those with three or more concussions were five times as likely to have Mild Cognitive Impairment and three times as likely to have significant memory problems compared to retirees without a history of concussion.

Nonetheless, some researchers believe that decoding the AD–brain injury connection will have implications far beyond the possibility of warding off dementia in head trauma patients. "It gives you insight into what may be the base mechanism for Alzheimer's disease," said Gareth W. Roberts, who coauthored several studies on the relationship between the two conditions before becoming Chief Executive Officer of the Cambridge, UK bioinformatics firm Proteom. "And once you have a feeling for what the core pathologic process is, you can ask, 'What kinds of things might stop that?'"

Other investigators envision similarly lofty applications. "I look upon head injury as a paradigm for understanding environmental risk factors for neurodegenerative diseases in general," said John Q. Trojanowski, Professor of Pathology and Laboratory Medicine at the University of Pennsylvania. For most patients, he noted, environmental factors are likely to far outweigh genetic influences in the etiology of neurodegenerative disease. "I think if we can 'crack' head trauma, it will open up ways of thinking about other environmental causes of these diseases."

WHAT HAPPENS AFTER BRAIN INJURY?

Recent studies have provided "very strong evidence that there is a connection between head trauma and at least some of the pathology of Alzheimer's disease," Dr. Trojanowski said. For example, in a report at the recent World Alzheimer Congress 2000, Steven T. DeKosky, and colleagues at the University of Pittsburgh Medical Center reported findings from neocortical samples taken from brain injury patients one and three days after injury. The samples, which were obtained by surgical resection and compared with postmortem samples from neurologically normal controls, revealed increases in amyloid precursor protein (APP), apolipoproteins E and D, and ß-amyloid (Aß). Many of the Aß deposits "had morphologic characteristics of classic amyloid plaques in AD," Dr. DeKosky and colleagues reported.

Several studies have found that Aß deposition occurs in a third of fatal head injury cases, even in children who survived only a few hours. The Aß is generally distributed throughout the brain; its presence does not correlate with cerebral contusions, increased intracranial pressure, or intracranial hematomas. Neurofibrillary tangles may also occur. The nature of pathology depends in part on injury severity—tangles do not seem to occur after mild trauma—but "I don't think there's much insight into how severe the injury has to be" to trigger AD-like pathology, Dr. Trojanowski said.

These changes make sense, Dr. Roberts said, if one accepts the view that Alzheimer's disease is largely an inflammatory process. APP is found in synapses, he noted, and "one of the things we do know happens after brain injury is synaptic remodeling." Moreover, electron microscopy shows that synapses are involved in amyloid plaque formation. This may be a repair process of some sort, he said, but "instead of being shut down when it is appropriate, it just carries on. It becomes a bit like arthritis, where mechanisms that should help you instead become chronically activated and disabling."

It should be noted, however, that the neuropathology of brain injury is by no means a carbon copy of the changes that occur in AD. For example, levels of growth inhibitory factor are increased in reactive astrocytes in experimentally induced brain injury, whereas these levels are reduced throughout the brain in AD. Moreover, the neocortical distribution of neurofibrillary tangles is more superficial in former boxers with dementia pugilistica, or punch drunk syndrome, than in AD patients.

HOW LARGE IS THE RISK?

Despite the array of pathologic evidence linking the disorders, the relationship between AD and head injury remains unsettled from an epidemiologic standpoint. Findings reported last year from the Rotterdam Study, for example, found no increased risk of AD in subjects with a history of head injury. Nonetheless, positive studies outnumber negative ones, and head injury is "becoming more accepted as being associated with the risk of AD," said Brenda L. Plassman, Director of the Program in Epidemiology of Dementia at Duke University Medical Center.

In a new report Dr. Plassman and colleagues performed telephone screening of more than 2,000 World War II veterans who had been hospitalized for head injury, pneumonia, or puncture wounds in 1944 or 1945. Subjects who screened positive for possible dementia underwent a three-hour exam that included neuropsychologic testing, neurologic examination, and DNA collection.

From 1940s armed forces hospital records, the researchers were able to estimate the severity of each subject's head injury, based on the occurrence of amnesia or skull fracture and the duration of unconsciousness. The findings revealed that "the more severe the injury, the greater the risk of AD and dementia"; the relative risks (compared with controls) ranged from about 2 for moderate head injury to 4 for severe injury. The findings are consistent with those from most other positive epidemiologic studies, Dr. Plassman said. "It's rather striking that all of these studies used different samples, methods, and criteria for head injury, yet all have odds ratios that are pretty close." The relative risk of AD after head injury is roughly similar to that reported for subjects heterozygous for the APOE*E4 allele, she added.

THE GENETIC CONNECTION

The role of genetic vulnerability is suggested by the fact that only a subset of brain injury patients develops amyloid pathology. Many investigators believe APOEgenotype is the key culprit. "There is a clear relationship between having an APOE*E4 allele and your likelihood of developing plaques after a head injury," Dr. Roberts said. "So in a sense the APOE–head injury story gives you the first genetic–environmental interaction in a neurologic disease." This relationship is consistent with APOE's proposed role in the maintenance and repair of neuronal membranes, synaptogenesis, and other processes. Indeed, researchers at the University of Glasgow reported earlier this year that the densities of the ß-amyloid peptides Aß-42 and Aß-40 in head injury patients were related in a dose-dependent manner to APOE*E4 endowment.

However, it is possible that in many cases head injury doesn't induce AD-like pathology so much as accelerate its arrival. A 1989 retrospective study found that a history of head injury was associated with earlier onset of AD. And a report from the Mayo Clinic suggested that AD rates were not elevated among subjects with a history of head trauma, but that the injury hastened the time to AD onset by about eight years.

FUTURE INTERVENTIONS

Can prompt, appropriate treatment after brain injury reduce or prevent the development of AD-like pathology? While the mouse model for AD that Dr. Trojanowski and others have been using has yielded interesting findings, the rodents' lack of tau pathology and "quirky" behavior did not allow for ideal testing of therapeutic interventions.

Until now, researchers have lacked a good animal model for studying the development of Alzheimer's disease. The transgenic mice used in the CNDR contain the human gene that produces the Ab protein. With the aid of techniques developed at the Penn Head Injury Center, Uryu and his colleagues were able to study how just mild repetitive head injuries could influence the progress of Alzheimer's disease.

Even without head trauma, these mice would eventually develop Ab plaques later in life. With the trauma, they produce symptoms of Alzheimer's disease at a remarkably increased rate.

"Here, we can clearly see a direct cause and effect relationship between repetitive concussions and Alzheimer's," said John Q. Trojanowski. "Using the head trauma model in these mice represents a step forward in our ability to understand the basic molecular mechanisms behind Alzheimer's disease. More importantly, we believe this model system can be used to screen for new medications in the search for a cure."

At present, "aside from telling football players and soccer players to either not play or to wear a helmet, there's not much in the way of interventions," Dr. Trojanowski noted. However, as researchers gain a better understanding of the relationship between trauma, risk factors, and genetic vulnerability, medical advice could theoretically be targeted to a patient's profile: "If you're APOE*E4 homozygous, you should really think twice about playing football. If you're heterozygous for APOE*E4, you'd better wear a helmet and take vitamin E and aspirin for the rest of your life."

Moreover, the inflammatory model of AD pathogenesis offers obvious potential for intervention. Epidemiologic studies have found a reduced rate of AD among people who regularly used nonsteroidal anti-inflammatory drugs. And a study in the Journal of Neurosciencefound that ibuprofen reduced not only inflammation, but Aß plaque burden in a transgenic mouse model for AD.

An interesting recent 2008 year study at Washington University in St. Louis and the University of Milan evaluated hour-by-hour measurements of the protein amyloid beta in 18 patients with severe brain injury as they were coming out of a coma.

"We were trying to understand why traumatic brain injury increases the risk of Alzheimer's disease," said Dr. David Brody of Washington University, who estimates that people with severe brain injuries have a two to four times greater risk of developing Alzheimer's disease.

The classic theory is that such injuries increase the amount of amyloid beta, which may accelerate the development of sticky clumps of amyloid plaque that is a hallmark of Alzheimer's disease.

To study the classic theory related to the increasing amount of amyloid beta, accelerating the development of sticky clumps of amyloid plaque, the teams placed a small catheter into the brains of the patients to sample fluid in the spaces between cells, where amyloid beta protein accumulates. Then, they took hourly measurements of the fluid to check levels of the protein.

"What we were expecting was that amyloid beta levels would be high immediately after the injury and fall over time," Brody said in a telephone interview. What they saw instead was a gradual increase in levels of this protein as patients recovered brain function. The better the patients got, the higher their amyloid beta levels rose. And in patients whose neurological function worsened, amyloid beta fell.

Brody said the finding suggests that amyloid beta in the human brain may be an indicator of how well brain cells are communicating, something studies in mice have suggested.

And while it also proves it is possible to directly measure amyloid beta in humans, "it raises a lot more questions than it answers," Brody said.

Sources and Additional Information:

http://www.neuropsychiatryreviews.com/oct00/npr_oct00_brain.html

http://www.reuters.com/article/healthNews/idUSPAT87667620080828

http://www.tangledneuron.info/the_tangled_neuron/2007/03/head_injuries_a.html

http://www.newscientist.com/article/dn12002-brain-injuries-unleash-alzheimers-threat.html

10 Types of Dementia that are NOT Alzheimer's

The term dementia is used broadly to describe a condition which is characterized by cognitive decline, but there are many different types of dementia. Although it is usually progressive, properly diagnosing dementia can reverse the effects and be treated and even cured completely by addressing the underlying cause. However, dementia caused by incurable conditions such as Alzheimer’s disease, are irreversible.

What are the different types of dementia?

Experts estimate that Alzheimer’s disease is the underlying cause of 60–80% of all dementia cases. However, there are many other conditions which can also cause dementia, which makes it vital for the patient to obtain accurate diagnosing of dementia early on in order to get proper treatment. Following are some of the most common types of dementia and their causes.

1. Vascular Dementia. 
   The second most common form of dementia, vascular dementia is caused by poor blood flow to the brain, which deprives brain cells of the nutrients and oxygen they need to function normally. One of the ten dementia types, vascular dementia can result from any number of conditions which narrow the blood vessels, including stroke, diabetes and hypertension.

2. Mixed Dementia. 
   Sometimes dementia is caused by more than one medical condition. This is called mixed dementia. The most common form of mixed dementia is caused by both Alzheimer’s and vascular disease.

3. Dementia with Lewy Bodies (DLB).
   Sometimes referred to as Lewy Body Disease, this type of dementia is characterized by abnormal protein deposits called Lewy bodies which appear in nerve cells in the brain stem. These deposits disrupt the brain’s normal functioning, impairing cognition and behavior and can also cause tremors. DLB is not reversible and has no known cure.

4. Parkinson ’s Disease Dementia (PDD).
   Parkinson’s disease is a chronic, progressive neurological condition, and in its advanced stages, the disease can affect cognitive functioning. Not all people with Parkinson’s disease will develop dementia, however. Dementia due to Parkinson’s is also a Lewy body dementia. Symptoms include tremors, muscle stiffness and speech problems. Reasoning, memory, speech, and judgment are usually affected.

5. Frontotemporal Dementia. 
   Pick’s disease, the most common of the frontotemporal dementia types, is a rare disorder which causes damage to brain cells in the frontal and temporal lobes. Pick’s disease affects the individual’s personality significantly, usually resulting in a decline in social skills, coupled with emotional apathy. Unlike other types of dementia, Pick’s disease typically results in behavior and personality changes manifesting before memory loss and speech problems.

6. Creutzfeldt-Jacob Dementia (CJD).
   CJD is a degenerative neurological disorder, which is also known as mad cow disease. The incidence is very low, occurring in about one in one million people. There is no cure. Caused by viruses that interfere with the brain’s normal functioning, dementia due to CJD progresses rapidly, usually over a period of several months. Symptoms include memory loss, speech impairment, confusion, muscle stiffness and twitching, and general lack of coordination, making the individual susceptible to falls. Occasionally, blurred vision and hallucinations are also associated with the condition.

7. Normal Pressure Hydrocephalus (NPH).
   Normal pressure hydrocephalus involves an accumulation of cerebrospinal fluid in the brain’s cavities. Impaired drainage of this fluid leads to the build-up and results in added pressure on the brain, interfering with the brain’s ability to function normally. Individuals with dementia caused by normal pressure hydrocephalus often experience problems with ambulation, balance and bladder control, in addition to cognitive impairments involving speech, problem-solving abilities and memory.

8. Huntington’s Disease. 
   Huntington’s disease is an inherited progressive dementia that affects the individual’s cognition, behavior and movement. The cognitive and behavioral symptoms of dementia due to Huntington’s include memory problems, impaired judgment, mood swings, depression and speech problems (especially slurred speech). Delusions and hallucinations may occur. In addition, the individual may experience difficulty ambulating, and uncontrollable jerking movements of the face and body.

9. Wernicke-Korsakoff Syndrome.
   Wernicke-Korsakoff syndrome is caused by a deficiency in thiamine (Vitamin B1) and often occurs in alcoholics, although it can also result from malnutrition,  cancer which have spread in the body, abnormally high thyroid hormone levels, long-term dialysis and long-term diuretic therapy (used to treat congestive heart failure). The symptoms of dementia caused by Wernicke-Korsakoff syndrome include confusion, permanent gaps in memory, and impaired short-term memory. Hallucinations may also occur.

10. Mild Cognitive Impairment (MCI).
    Dementia can be due to medical illness, medications and a host of other treatable causes. With mild cognitive impairment, an individual will experience memory loss, and sometimes impaired judgment and speech, but is usually aware of the decline. These problems usually don’t interfere with the normal activities of daily living. Individuals with mild cognitive impairment may also experience behavioral changes that involve depression, anxiety, aggression and emotional apathy; these can be due to the awareness of and frustration related to his or her condition.

Source:

http://www.gilbertguide.com/articles/10-types-of-dementia-that-arent-alzheimers-how-theyre-diagnosed/