Neuroscience Featured at MMC’s Chinese Medical Program Health Workshop

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Another reason to take snoring seriously! Sleep apnea linked to strokes.

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Sleep apnea, the disorder that causes a person to stop breathing suddenly while sleeping, is already known to increase the risk of high blood pressure, heart failure, and daytime sleepiness.

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A new study suggests that the sleep disorder is also linked with small brain lesions and a symptomless form of stroke, known as silent stroke.

In the study, 56 men and women ( aged 44 to 75 years) who’d had a recent stroke or TIA underwent overnight polysomnograms.  91% had sleep apnea.

Furthermore, having more than five episodes of sleep apnea in a night was linked with having multiple extra “silent strokes” on their brain imaging studies.

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Silent strokes don’t cause any symptoms as they occur, so a person typically doesn’t know he or she has suffered one, but they can eventually lead to memory loss and difficulties with walking, as their effects accumulate over the years.”

Yet another reason to take the on-line sleepiness test, and if your score is >10 see a sleep specialist and/or get an overnight polysomnogram in a certified sleep laboratory.

New Brain Imaging for Alzheimer’s Disease

Amyloid proteins in normal brains (left) and abnormal ones (right) visualized with GE Healthcare’s PET tracer flutemetamol.

Alzheimer’s disease is the commonest cause of dementia, and as the population is aging, it’s prevalence is increasing.

Alzheimer’s disease presently affects 5 million Americans aged 65 or older.  Without a major medical breakthrough, by 2025 this number is expected to have risen to 7 million, and by 2050 it could reach 14 million

The costs of caring for Alzheimer’s patients is also increasing, estimated at $203 billion in 2013, and $1.2 trillion by 2050,  including a 500% increase in combined Medicare and Medicaid spending.

Clearly, finding that major therapeutic breakthrough is crucial, and had been identified as a priority by the Obama Administration.

The first barrier to starting any clinical trial is accurate case ascertainment – we have to be able to correctly identify early Alzheimer’s patients for new experimental treatments.

So far, the only definitive test for Alzheimer’s disease is examination of brain tissue (usually obtained at autopsy) for identification of the characteristic pathologic changes of Amyloid paque and Neurofibrillary tangles:

Alzheimer’s disease is usually diagnosed based on  clinical criteria, but many patients diagnosed this way are later found to have other causes of dementia when their brains are examined at autopsy, in other words they were misdiagnosed as Alzheimer’s.

With more research trials and potential new effective therapies on the horizon, it is going to become more important to establish a diagnosis of Alzheimer’s more accurately and earlier, perhaps even pre-symptomatically (i.e. mild cognitive impairment or MCI), so that treatment to reverse the build up of plaque and tangles is more likely to be effective.

New positron emission tomography (PET) technology can actually quantify the amount of amyloid in affected patients’ brains.  A recently published small study showed a very high correlation between amyloid identified on PET scans and amyloid plaque demonstrated in brain biopsy specimens taken from demented patients.

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These tests are going to be very important for research studies.

However, don’t rush to your private doctor’s office asking to have one done just yet!

Although approved by the FDA, these test are not yet covered by Medicare or other insurance covering, and cost between $1500 and $3000.

Furthermore, these are new tests, and their role in clinical neurology practice in still unclear.

Some of these issues were recently clarified in a report by the Amyloid Imaging Taskforce convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging:

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This taskforce concluded that a Amyloid PET scan is indicated for:

Progressive memory impairment or dementia with atypical features, where a positive PET would indicate definite Alzheimer’s, and a negative scan would rule it out and lead to further testing for other possible causes.

Younger patients (aged 50-65) with suspected Alzheimer’s, in whom making a definitive diagnosis is crucial for log term planning and future medical decision making.

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The taskforce concluded that a Amyloid PET scan is unnecessary and/or unhelpful for:

Patients with typical Alzheimer’s disease,

Determining the severity of dementia,

Asymptomatic patients with a family history of dementia or positive apolipoprotein E4 status,

Patients who complain of memory loss but have no objective findings,

Testing purely for medico-legal, disability, insurance or employment related issues.

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Find out more:

Click here to find out more about Memory loss, Mild Cognitive Impairment and Alzheimer’s.

Click here to find out more about diagnosing Alzheimer’s.

Links to the Alzheimer’s Association, Alzheimer’s Foundation of America and CDC Healthy Brain Initiative

Diagnostic testing for Alzheimer’s?

The only definitive test for Alzheimer’s disease is examination of brain tissue (usually obtained at autopsy) for identification of the characteristic pathologic changes of Amyloid paque and Neurofibrillary tangles:
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Alzheimer’s disease is usually diagnosed based on  clinical criteria, but many patients diagnosed this way are later found to have other causes of dementia when their brains are examined at autopsy, in other words they were misdiagnosed as Alzheimer’s.

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With more effective new therapies on the horizon, it is going to become more important to establish a diagnosis of Alzheimer’s more accurately and earlier, perhaps even pre-symptomatically (i.e. mild cognitive impairment or MCI), so that treatment to reverse the build up of plaque and tangles is more likely to be effective.

There has been interest in Apoprotein E (APOE) genotype and Alzheimer’s risk. APOE genes come in 3 types (2-4).  If you have 2 copies of  APOE4 (1-2% of the population)  you are 15 times more likely to develop Alzheimer’s than averages, and if you have one copy of APOE4 you have are 3 times more likely to develop Alzheimer’s than average.   Clearly, there is an association between APOE4 genoytpe and Alzheimer’s.  However, not every patient with APOE4 develops Alzheimer’s, and you can develop Alzheimer’s without APOE4, so APOE genotyping is not recommended as a diagnostic test.

The ratio of cerebrospinal fluid levels of beta-amyloid and tau proteins can be predictive for Alzheimer’s, but this test requires a lumbar puncture, and is inconclusive in many cases.

Magnetic resonance imaging (MRI) of the brain has shown selective atrophy of the hippocampus in patients with early Alzheimer’s (a) vs. normal elderly controls (b), and this technique has been proposed as a diagnostic test for Alzheimer’s, but requires special computerized imaging processing not available at most imaging centers.
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Fluorodeoxyglucose posititon emission tomogrpahy (FDG-PET) shows reduced metabolic activity (uptake of sugar) in the temporal and parietal lobes of patients with early Alzheimer’s (these regions are darker) vs. normal elderly controls (these regions are brighter), and this test is FDA approved, covered by Medicare, and widely available at imaging centers around the counrty:
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A recent study compared the results of MRI, FDG-PET and analysis of CSF biomarkers  in 97 MCI patients, to see which was best for predicting who would convert to Alzheimer’s first. During a mean follow-up of almost 3-years, 43 patients progressed to AD and 54 did not. Of the 3 tests, an abnormal FDG-PET was most predictive.

Before you all rush out and get your FDG-PET to see if you are high risk for Alzheimer’s, be warned that results may be unreliable when the test is performed at an inexperienced center. Data presented at this year’s American Academy of Neurology meeting showed that up to 2/3 of patients referred to a University dementia program had been misdiagnosed with Alzheimer’s dementia based on misread FDG-PET scans performed at community imaging centers.

The Amyvid™ (Florbetapir F 18) PET scan, which was FDA approved this year, actually quantifies the amount of amyloid plaque in affected patients’ brains (bright), and is probably a more promising new PET technique for predicting Alzheimer’s disease. However, this test is not yet covered by Medicare or other insurance covering, and costs between $1500 and $3000:

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In sum, the hope for the future is that with earlier and more accurate diagnosis, future treatments could target Alzheimer’s in its earliest stages, before irreversible brain damage or mental decline has occurred.  However, it is clear that none of the available diagnostic tests are perfect, and although promising, amyloid plaque PET scans are not yet covered by Medicare, so for now we mostly continue to make do with clinical diagnostic criteria.