The neurobiological hallmarks of Alzheimer’s disease are amyloid plaques and neurofibrillary tangles, both of which are specific neurological changes that occur in the brain at a microscopic level. This is why a diagnosis of Alzheimer’s disease can be so difficult in a living person: We can’t look at the brain under a microscope to check for plaques and tangles, which would be the only way to diagnose Alzheimer’s definitively. Currently, this can only occur by autopsy.
Recent imaging advances allow us to see the plaque buildup (amyloid)
or tangles (tau) by way of an amyloid PET scan or tau PET scan, respectively. Amyloid
PET scans are FDA-approved, but rarely ordered because insurance does not yet
cover the procedure. Tau PET scans are used in research but have not yet been
FDA-approved. Both procedures are costly and involve the injection of an
isotope—a dye that binds to the amyloid or tau protein and lights up when the
patient is in the scanner.
We can also measure for byproducts of plaques and tangles by looking in cerebrospinal fluid, the fluid that circulates in the brain and spinal cord. Insertion of a needle into the spinal cord allows for the withdrawal of fluid that can then be assayed, much like blood, for measures of specific components.
In unaffected individuals, amyloid levels in cerebrospinal
fluid are high—an indication that amyloid is being cleared from the brain as it
should be—and tau levels are low. For people with Alzheimer’s disease, the
opposite is true: There are low levels of amyloid in cerebrospinal fluid and
high levels of tau. Specific cutoff points for amounts of amyloid and tau to
aid in diagnosis have not been fully standardized yet.
The quest for easily obtainable biological markers of Alzheimer’s disease is ongoing and far-reaching. Numerous groups are studying possibilities for blood markers. Genetic testing is also on the rise, but inconclusive because most forms of Alzheimer’s disease cannot be predicted by genes alone.
A group of researchers at Boston Medical Center recently reported that eye fluid may contain biological markers of Alzheimer’s disease. The researchers utilized eye fluid samples that would otherwise have been discarded from 80 patients who underwent eye surgery. They found that levels of amyloid and tau in eye fluid correlated with performance on a cognitive test: lower levels of these proteins correlated with lower cognitive test scores.
Correlation does not prove causation, so much more research
needs to be done. In fact, there have been other groups who have advocated and
studied the potential use of retinal examination for the presence of amyloid
plaques. The premise is that the retina is an extension of the brain. Amyloid
plaques in the brain have been correlated with amyloid plaque in the retina.
Experimental eye drops that stain for amyloid may be used with a medical device to detect the presence of amyloid plaque in the retina, which then may correlate with amyloid plaque in the brain. Such studies have also received media attention. And, another recently published study explores the relationship between dental gum plaque and brain plaque.
While none of these techniques is currently available for
clinical use, as none have met the FDA criteria for approval, they are all a
testament to the need for efficient, accessible diagnostic tools for
Alzheimer’s disease. Time is brain and early diagnosis is critical to finding a
cure. And, you never know, the answer could be more than what meets the eye.
For more information about Alzheimer’s disease diagnosis and
access to potential treatments, please contact The CRCNJ at 973-850-4622.
Could A Biological Marker for the Diagnosis of Alzheimer’s Disease be in the Eye of the Beholder?
The neurobiological hallmarks of Alzheimer’s disease are amyloid plaques and neurofibrillary tangles, both of which are specific neurological changes that occur in the brain at a microscopic level. This is why a diagnosis of Alzheimer’s disease can be so difficult in a living person: We can’t look at the brain under a microscope to check for plaques and tangles, which would be the only way to diagnose Alzheimer’s definitively. Currently, this can only occur by autopsy.
Recent imaging advances allow us to see the plaque buildup (amyloid) or tangles (tau) by way of an amyloid PET scan or tau PET scan, respectively. Amyloid PET scans are FDA-approved, but rarely ordered because insurance does not yet cover the procedure. Tau PET scans are used in research but have not yet been FDA-approved. Both procedures are costly and involve the injection of an isotope—a dye that binds to the amyloid or tau protein and lights up when the patient is in the scanner.
We can also measure for byproducts of plaques and tangles by looking in cerebrospinal fluid, the fluid that circulates in the brain and spinal cord. Insertion of a needle into the spinal cord allows for the withdrawal of fluid that can then be assayed, much like blood, for measures of specific components.
In unaffected individuals, amyloid levels in cerebrospinal fluid are high—an indication that amyloid is being cleared from the brain as it should be—and tau levels are low. For people with Alzheimer’s disease, the opposite is true: There are low levels of amyloid in cerebrospinal fluid and high levels of tau. Specific cutoff points for amounts of amyloid and tau to aid in diagnosis have not been fully standardized yet.
The quest for easily obtainable biological markers of Alzheimer’s disease is ongoing and far-reaching. Numerous groups are studying possibilities for blood markers. Genetic testing is also on the rise, but inconclusive because most forms of Alzheimer’s disease cannot be predicted by genes alone.
A group of researchers at Boston Medical Center recently reported that eye fluid may contain biological markers of Alzheimer’s disease. The researchers utilized eye fluid samples that would otherwise have been discarded from 80 patients who underwent eye surgery. They found that levels of amyloid and tau in eye fluid correlated with performance on a cognitive test: lower levels of these proteins correlated with lower cognitive test scores.
Correlation does not prove causation, so much more research needs to be done. In fact, there have been other groups who have advocated and studied the potential use of retinal examination for the presence of amyloid plaques. The premise is that the retina is an extension of the brain. Amyloid plaques in the brain have been correlated with amyloid plaque in the retina.
Experimental eye drops that stain for amyloid may be used with a medical device to detect the presence of amyloid plaque in the retina, which then may correlate with amyloid plaque in the brain. Such studies have also received media attention. And, another recently published study explores the relationship between dental gum plaque and brain plaque.
While none of these techniques is currently available for clinical use, as none have met the FDA criteria for approval, they are all a testament to the need for efficient, accessible diagnostic tools for Alzheimer’s disease. Time is brain and early diagnosis is critical to finding a cure. And, you never know, the answer could be more than what meets the eye.
For more information about Alzheimer’s disease diagnosis and access to potential treatments, please contact The CRCNJ at 973-850-4622.
From Mice to Wo/Men: A Novel Approach to Treating Alzheimer’s Disease
Hot off the press, researchers at MIT share their characteristic out-of-the-box approach to solving the underlying problem of Alzheimer’s disease. Leave it to the MIT braniacs to design a medical device that may treat Alzheimer’s AND do so by applying a relatively simple, known concept to a very complex puzzle.
Researchers at the Picower Institute for Learning and Memory are using 40 hertz (hz) signals, in different sensory modalities—light and sound—to help restore gamma activity in the brain. In a mouse model, the generation of gamma brain wave activity initiated by exposure to 40 hz light and sound stimulation resulted in a decrease in amyloid plaques and phosphorylated tau proteins—both hallmarks of Alzheimer’s disease—in different brain regions.
An old adage in the research community is: “We’ve cured a thousand mice, but if we could only cure one (wo)man….” That is the true test of a viable treatment. The utility and value of this medical device is currently being tested in humans and we, at The Cognitive and Research Center of New Jersey, have been selected as a site for this study, aMulti-Center Study of Sensory Stimulation to Improve Brain Function, also known as the Overture Study, sponsored by Cognito Therapeutics, Inc.
The Overture Study is a Phase I/II randomized, controlled, single-blind multi-center clinical trial using the GammaSense Stimulation device to study safety, adherence rates and efficacy in subjects with Alzheimer’s disease or Mild Cognitive Impairment due to Alzheimer’s disease. Eligible subjects must be 55 years or older, obtain a Mini-Mental Status Examination score of 14 to 26 and have someone who can serve as a study partner. People who have profound hearing or visual impairment, seizure disorder, implantable devices that prohibit MRIs, or who are taking memantine (Namenda or Namzaric) would not be eligible. Overall, the goal is to enroll a total of 60 subjects across sites.
Subjects who pass screening will be randomized at a ratio of 2:1 treatment to control, which means that each subject has about a 67 percent chance of receiving active treatment and a 33 percent chance of receiving placebo. Neither the participants nor the site raters will know whether a subject is on treatment or receiving a sham, as knowing treatment group could cause biases.
Subjects will be required to utilize the device at home for 60 minutes daily for six months. During that time, subjects and study partners will come to the site periodically to undergo various cognitive tests and scales of behavioral functioning. Subjects will also receive multiple amyloid positron emission tomography (PET) scans.
Contact us to learn more about the Overture study and whether you or a loved one are a candidate, as we are actively enrolling for this trial at The Cognitive and Research Center of New Jersey.
Good Night, Good Brain: The Medicinal Powers of Sleep
The connection between sleep apnea—a cessation of oxygen to the brain during sleep—and cognitive impairment has long been recognized. However, the reason people with sleep disorders are at greater risk forcognitive decline has not been fully understood.
Small changes to the blood vessels in the brain are suspected but, often, these patients will have “normal” brain scans and typical clinical workups fail to reveal an underlying condition. Of course, lack of a good night’s sleep is likely to result in fatigue, which may impact attention and other cognitive functions, as well as mood. But, is there another common thread?
A study presented at the 2019 American Academy of Neurology meeting shed some new light on this question. Researchers at the Mayo Clinic Study of Aging found that study participants who snored and had sleep apnea were more likely to have a buildup of tau, a toxic protein found in Alzheimer’s disease, particularly in an area of the brain called the entorhinal cortex, which helps govern a number of facets of memory.
In a living patient, measures of tau can only be made based on specialized tau PET imaging or analysis of cerebral spinal fluid, whichare not part of a typical clinical evaluation but are often utilized in clinical research studies.
The powerful effects of sleep have also been touted by a growing body of research showing that, in normal brain functioning, restful sleep provides the conduit by which the brain rids itself of toxic buildup – “junk” – by way of cerebrospinal fluid. This is why I urge my patients to prioritize good sleep hygiene and to consult with a sleep specialist for sleep problems.
Good Sleep Habits
Here are some ways to cultivate good sleep habits and sleep hygiene:
Good sleep provides one very important way of promoting healthy brain aging and reducing risk factors for dementia. It turns out that so-called “beauty sleep” is much more than skin-deep.
If you, or a loved one, are concerned about cognitive change caused by a sleep or other disorder, contact us at The Cognitive and Research Center of New Jersey to see how we can help.
Could Your Dark Brew Be Protecting You Against Alzheimer’s Disease?
As I savor each sip of my dark roast brew, I am delighted by a recently published article about the potentially neuroprotective effects of dark roast coffee. Canadian researchers at the Krembil Research Institute and University of Toronto compared light roast, dark roast, and decaffeinated dark roast coffee extracts on mouse model brains ridden with amyloid plaques and neurofibrillary tangles, typical of Alzheimer’s disease. Six different components within the coffee were tested for their impact on reducing the buildup of amyloid and tau proteins that comprise the plaques and tangles underlying Alzheimer’s disease.
Interestingly, caffeine, which has been touted by some as helpful to cognition, had no effect on the accumulation of amyloid and tau proteins. Rather, phenylindane, formed during the process of roasting coffee beans, was the only coffee bean component of the six tested (the others were caffeine, chlorogenic acid, quinic acid, caffeic acid, and quercetin) that inhibited both amyloid and tau proteins. This is the first report of its kind and lends support to the possibility of dark coffee roasts (both caffeinated and decaffeinated alike) protecting against the biological hallmarks of Alzheimer’s disease.
Does this mean we should all start sipping dark roasts as our miracle cure for Alzheimer’s disease? Of course, not – or, at least, not yet. Further studies are needed to better understand the role and optimal dosing of phenylindane and whether or not effects are replicated in humans. It is also important to recognize that excessive amounts of caffeine, as well as sugar and other ingredients often added to coffee, may be counter-productive. We just don’t have the data yet. But, I appreciate the scientific rigor of this study, and others like it, beginning to document the potentially positive effects of lifestyle and nutritional factors on the brain. And, as we await the findings of future studies, I will continue to enjoy moderate amounts of that ancient brew, and the darker the better!
If you are interested in learning more about the role of lifestyle factors in healthy brain aging, consider attending one of my upcoming talks, The CRCNJ Speaker’s Series, or participating in the individualized Psychoeducational Series, only offered at The CRCNJ. Contact us today for more information or to schedule your consultation.
When It’s “Not Alzheimer’s”
Several weeks ago, Ted Turner, 79-year old billionaire, CNN founder, and philanthropist, announced that he had dementia with Lewy bodies. When interviewed, he was not able to provide information about DLB, or readily recall its name, but expressed gratitude that it was “not Alzheimer’s.” Following in the footsteps of this disclosure was a recent article in The New York Times describing the proactive efforts of Laurie Scherrer, a Pennsylvania resident diagnosed with Alzheimer’s disease and frontotemporal dementia at age 55. So, what does it mean to have dementia that is not Alzheimer’s?
Dementia refers to global cognitive decline that is significant enough to interfere with daily functioning. While Alzheimer’s disease is the most common cause of dementia in people aged 65 years and older, there are numerous other causes of age-related dementia. In this regard, dementia can be thought of as a symptom which may be caused by a number of different diseases, such as dementia with Lewy bodies, frontotemporal dementia, cerebrovascular dementia, and Parkinson’s disease. Each type of dementia can be categorized by the specific changes that occur in the brain at a microscopic level. The exact symptoms evident in each person depends on the precise location of brain change as well as the unique brain circuitry of each individual, dependent on their life experiences and genetic predispositions. This is why no two people with dementia, even with the same type of dementia, have exactly the same symptoms. The brain is like real estate: it’s all about location, location, location.
Age-related dementias are not mutually exclusive. This means that just because a person has one type of dementia does not mean they can’t also have another type of dementia too. In fact, having dementia puts one at a higher risk for developing other dementias.
Knowing what type(s) of dementia a person has is important to planning, understanding symptoms and prognosis, and accessing treatment options and supportive resources. A comprehensive evaluation is the first step to proper diagnosis and treatment planning. If you are concerned about signs of cognitive decline, contact The Cognitive and Research Center of New Jersey to set up an evaluation and learn about interventions, including clinical trials and supportive resources. Time is brain. Call today.