Sunday, May 21

Diagnosing Dementia: Alzheimer's May Really Be Mini-Strokes

Memory problems are too quickly diagnosed as Alzheimer's. (In Alzheimer's, the culprit is amyloid-plaque in the brain.) New research shows a more common memory-culprit may be vascular dementia, caused by stroke, mini-stroke and high blood pressure. Learn the difference and why the right diagnosis effects therapy and treatment.

Alzheimer's is connected to sticky plaques made of beta-amyloid that choke brain cells, thereby causing dementia. People may act like they have Alzheimer's when they really have vascular dementia. Vascular dementia is caused by vascular events (related to blood vessels) such as strokes and mini-strokes, so treatment is different. (Mini-strokes occur in the brain when blood vessels clog up or burst. They can accumulate slowly and can go unnoticed for years.)

For example, the damage caused by plaque is typically treated with acetylcholinesterase inhibitors like Aricept®. These drugs target the nervous system. Vascular problems like mini-strokes are treated with blood-targeting medications and therapies.

Alzheimer's disease and vascular dementia are two types of dementia that are common in the elderly. A person's dementia can even be caused by a combination of the two, called "Mixed Dementia."

With today's technology, both vascular brain injury as well as beta-amyloid plaque can be detected in the brain. They both cause memory and thinking problems, called "cognitive impairment". If the cognitive impairment is strong and interferes with a typical person's day, it is called dementia. If it is mild, it is called MCI (Mild Cognitive Impairment).

Until now, doctors generally assumed that when they saw cognitive impairment, it was probably from plaque building up in the brain. Treatment and therapy were given accordingly. New research is showing that vascular brain injury from strokes or the mini-strokes often caused by high blood pressure may deserve the greater part of their attention.

A study at the Alzheimer’s Disease Research Center at UC Davis has found that vascular brain injury from conditions such as high blood pressure and stroke are greater risk factors for cognitive impairment among non-demented older people than is the deposition of the amyloid plaques in the brain that long have been implicated in conditions such as Alzheimer’s disease.
Bruce Reed
Bruce Reed

Published online early today in JAMA Neurology (formerly Archives of Neurology), the study found that vascular brain injury had by far the greatest influence across a range of cognitive domains, including higher-level thinking and the forgetfulness of mild cognitive decline.

The researchers also sought to determine whether there was a correlation between vascular brain injury and the deposition of beta amyloid (Αβ) plaques, thought to be an early and important marker of Alzheimer’s disease, said Bruce Reed, associate director of the UC Davis Alzheimer’s Disease Research Center in Martinez, Calif. They also sought to decipher what effect each has on memory and executive functioning.

“We looked at two questions,” said Reed, professor in the Department of Neurology at UC Davis. “The first question was whether those two pathologies correlate to each other, and the simple answer is ‘no.’ Earlier research, conducted in animals, has suggested that having a stroke causes more beta amyloid deposition in the brain. If that were the case, people who had more vascular brain injury should have higher levels of beta amyloid. We found no evidence to support that.”

"The second,” Reed continued, “was whether higher levels of cerebrovascular disease or amyloid plaques have a greater impact on cognitive function in older, non-demented adults. Half of the study participants had abnormal levels of beta amyloid and half vascular brain injury, or infarcts. It was really very clear that the amyloid had very little effect, but the vascular brain injury had distinctly negative effects.”

“The more vascular brain injury the participants had, the worse their memory and the worse their executive function – their ability to organize and problem solve,” Reed said.

The research was conducted in 61 male and female study participants who ranged in age from 65 to 90 years old, with an average age of 78. Thirty of the participants were clinically “normal,” 24 were cognitively impaired and seven were diagnosed with dementia, based on cognitive testing. The participants had been recruited from Northern California between 2007 to 2012.

The study participants underwent magnetic resonance imaging (MRI) ― to measure vascular brain injury ― and positron emission tomography (PET) scans to measure beta amyloid deposition: markers of the two most common pathologies that affect the aging brain. Vascular brain injury appears as brain infarcts and “white matter hyperintensities” in MRI scans, areas of the brain that appear bright white.

The study found that both memory and executive function correlated negatively with brain infarcts, especially infarcts in cortical and sub-cortical gray matter. Although infarcts were common in this group, the infarcts varied greatly in size and location, and many had been clinically silent. The level of amyloid in the brain did not correlate with either changes in memory or executive function, and there was no evidence that amyloid interacted with infarcts to impair thinking.

Reed said the study is important because there’s an enormous amount of interest in detecting Alzheimer’s disease at its earliest point, before an individual exhibits clinical symptoms. It’s possible to conduct a brain scan and detect beta amyloid in the brain, and that is a very new development, he said.

“The use of this diagnostic tool will become reasonably widely available within the next couple of years, so doctors will be able to detect whether an older person has abnormal levels of beta amyloid in the brain. So it’s very important to understand the meaning of a finding of beta amyloid deposition,” Reed said.

“What this study says is that doctors should think about this in a little more complicated way. They should not forget about cerebrovascular disease, which is also very common in this age group and could also cause cognitive problems. Even if a person has amyloid plaques, those plaques may not be the cause of their mild cognitive symptoms.”

Other study authors include Natalie Marchant of UC Berkeley and the Buck Institute for Research on Aging; Roxana Dhada and William Jagust of UC Berkeley; Charles DeCarli and Dan Mungas of UC Davis; Stephen Kriger and Micheal Weiner of UC San Francisco and Nerses Sanossian, Wendy Mack and Helena Chui of the University of Southern California.

The research was supported by grants number AG012435, AG00266 and AG10129 from the National Institutes of Health.

The UC Davis Alzheimer's Disease Center is one of only 27 research centers designated by the National Institutes of Health's National Institute on Aging. The center's goal is to translate research advances into improved diagnosis and treatment for patients while focusing on the long-term goal of finding a way to prevent or cure Alzheimer's disease. Also funded by the state of California, the center allows researchers to study the effects of the disease on a uniquely diverse population. For more information, visit alzheimer.ucdavis.edu.

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  1. I guess that this imporntant research article is a "turning point ' in AD research , and
    It research article can be considered as a milestone paper , tbat proved that one of the main starters of AD and others age-related dementias are the ageing-related macro and microvascular brain disorders.

    The article comproves again that the betamyloid acccumulation it is more for a "witness" (some times a toxic witness) than the culprit of dementias as AD.

  2. Continuing :

    None researcher or physician waits to treat a chronic Heart failure with “the drug" for the heart or with only One drug, once researchers and cardiologists realizes that chronic heart failures are very complex Heart diseases , that have to be treated with an association of drugs that have synergistic effects to treat the heart failures.
    I guess that neuroscientists and neurologists , following the example of the treatment of Heart failures , can not wait to treat so severe Brain Failures related to vascular and neurons ageing , as the brain diseases that leads to dementias (as the late onset AD dementia type and others ageing-related dementias types) only searching for “the drug”to treat so complex brain diseases as dementias , that starts with micro and macrovascular ageing, and with neurons and astrocytes ageings as in dementias in elderly patients.

    As researchers are at last searching for drugs that treat the brain vascular disorders (that looks to be one of the main startes of dementias) they could starts too make trials with drugs and supplements that can control or treat the CONSEQUENCES of such brain Vascular disorders described in the amazing research article of professor dr. Bruce Reed (from the UC Davis AD Center).

    As is well known, some of the pathological consequences of the brain vascular aging are in a sequence and at the same time in a vicious circle the :

    -High accumulation of peroxinitrites

    -Neurons and astrocytes mitochondrial disorders (leading to brain energy failure)

    -Biochemical,metabolical and molecular neurons and astrocytes disorders

    -Glucose transport and glucose metabolization brain disorders

    -Brain energy failure leading to neurons apoptosis and to dementia symptons

    -And at last, neuroinflammation. (and controlling the disorders above it can protects upstreams against neuroinflammation too).

    None researcher or physician thinks that they can find “the drug” to treat that long sequence of pathological disorders that follow the brain vascular disoreders as described above , or would think that if they treat only one or a couple of the disorders above , they could find “a cure” for dementias.

    But there are some dietary supplements that looks to works in an empirical way , controlling some of the neurons disorders described above .

    1. For example , as I described in others posts , my aunt that have advanced dementia takes the following supplements since 2009 ,in an empirical way , but under permission and strict supervision of her PHYSICIAN , and the supplements in an empirical way , are controlling her hallucinations ,delusions, agressiviness ,insomnia,agitation , cryings, yells,that she had most the time of the day and most the time of the night before she started to takes that dietary supplements.
      We are using the NPI-Q scale (NEUROPSYCHIATRIC INVENTORY QUESTIONNAIRE), still in a empirical way , as a scale to mensure the enhancings of mood and behavior using that dietary supplements. (We can find the NPI-Q scale searching in Google).
      In an empirical way we are giving:
      1) L-CARNOSINE : 60 miligrams three times a day. CARNOSINE , it is a peroxinitrite scavenger, antiglycating supplement, a mild heavy metal chelator, and a mitochondrial funtion improver,and works controlling the excessive production of the neuroinflammatory citokines as IL6, IL8, and TNF alpha.
      2) ACETYL L CARNITINE (ALCAR) - 30 to 80 miligrams three times a day.(it is NOT L-carnitine , but is ACETYL L-CARNITINE) . ACETYL L CARNITINE is a peroxinitrite scavenger, an alternative fuel to the neurons, increase fatty acids metabolization (as the metabolization of coconut oil) ,and is a mitochondrial funtion improver. All these propierties increase the energy to the neurons.
      3) EXTRA VIRGIN COCONUT OIL - One tea spoon of this dietary supplement three times a day.( in the empirical doses as described in the anedoctal report of doctor Mary Newport). If the patient have diarrhea even with these small doses , the caregivers , still in an empirical way makes massages with the oil in the thin skin of the arms with the tea spoon of the oil ,once the coconut oil has a comproved fast trans-cutaneous absortion (according articles in PubMed)
      4) L-GLUCURONOLACTONE : 300 to 400 miligrams miligrams 2 to 4 times a day. GLUCURONOLACTONE (we got the best effects with this supplement) it is an alternative fuel to the neurons, peroxinitrite scavenger, a mild heavy metal chelator,and a mitochondrial funtion improver, and a detoxifying substance produced by our bodies and present in fruits and vegetables too. Glucuronolactone byproducts of metabolization are the glucaric acid (found in apples and broccoli) and glucaro 1,4 lactone. We can find lots of articles in PubMed about the protective effects of the glucaro 1,4 lactone (the byproduct of glucuronolactone metabolization).
      5) GLUCOSAMINE SULPHATE : 200 miligrams 3 to 4 times a day. GLUCOSAMINE SULFATE (the so called joint supplement) is an alternative fuel to the neurons, a peroxinitrite scavenger and looks to stabilizes the tau microtubules in an empirical way, based in some articles in PubMed.
      A lot of friends of mine , after my anedoctal report , are giving to their relatives ,in an empirical way too , the dietary supplements described above , under permission and supervision of the PHYSICIAN of the patients with different types of dementia ,with the same amazing effects to enhances cognition,mood and controlling the odd behaviors.(they use too the NPI-Q scale in to mensure the improves in mood and behavior). Only the PHYSICIAN of the patient can gives permissions,and knows the right supplements and the right doses to each supplement. Please , do NOT gives none supplement without the permission and supervision of the PHYSICIAN of the patient.
      The goal of this anedoctal report it is as a SUGGESTION to researchers , once maybe researchers could use that dietary supplements , as a biochemical and pharmacological BASIS to develops more EFFECTIVE drugs to control the consequences of the vascular ageing disorders of the brain ,controlling in consequence the dementia symptons.

  3. Brain vascular disorders leads to Impaired brain glucose metabolism (that means brain energy deprivation) that leads , between others disorders , to a Decrease in tau o-glcnacylation (it Decrease is responsible to tau accumulation).Then,using the rational thinking ,or based in logic, researchers concluded that if they find a substance (or a supplement) that at the Same Time Increases Cells Energy and Increases too the tau o-glcnacylation , it substance or dupplement can gives neuroprotection by multimodal mechanisms , including by treating the tau accumulation (a disorder that is related to most neurodegenerative diseases). As we can see in the reference articles bellow , GLUCOSAMINE looks to have all that neuroprotective propierties ...
    As described above , impaired brain glucose metabolism (for example , by mitochondrial disorders (7)) leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylation (2) , linking lower brain glucose metabolism and tau pathology in Alzheimer's disease (2) , (3) ,and as increased O-GlcNAcylation increases non-amyloidogenic α-secretase processing, resulting in increased levels of the neuroprotective sAPPα fragment and decreased Aβ secretion (1) , and considering that GLUCOSAMINE works as an alternative fuel ,as a improver of mitochondrial function (9), and that cells incubated with glucosamine,the researchers observed increased O-GlcNAcylation (8), maybe , researchers could starts to use glucosamine as a precursor of some synthetic drug with the same mechanism of action of glucosamine , but with more effectiviness to treat taupathies .

    . 2006 Mar – authors : Gong CX, Liu F, Grundke-Iqbal I, Iqbal K. - Source - Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities , USA.
    3) REDUCED O-GLCNACYLATION LINKS LOWER BRAIN GLUCOSE METABOLISM AND TAU PATHOLOGY IN ALZHEIMER'S DISEASE. Brain. 2009,Jul - Liu F, Shi J, Tanimukai H,Gu J, Gu J, Grundke-Iqbal I, Iqbal K, Gong CX. - Source - Department of Neurochemistry, N.Y,USA
    5) O-GLCNACYLATION REGULATES PHOSPHORYLATION OF TAU:A MECHANISM INVOLVED IN ALZHEIMER'S DISEASE. 2004 Jul 12.- Authors Liu F, et al.New York State Institute for Basic Research in Developmental Disabilities,USA.
    6) "DOES O-GLCNACYLATION PLAY A ROLE IN NEURODEGENERATIVE DISEASES?" Expert Rev Proteomics. 2005 Apr - Lefebvre T and colleagues-France.
    7) MITOCHONDRIAL FAILURES IN ALZHEIMER'S DISEASE. Am J Alzheimers Dis Other Demen.,Mark Smith,George Perry and colleagues, 20042


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