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From the Townsend Letter
January 2015

Anti-Aging Medicine
Advancements in Diagnostics to Assess Alzheimer's Disease
by Ronald Klatz, MD, DO, and Robert Goldman, MD, PhD, DO, FAASP
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Alzheimer's Disease International reports that as of 2013, there were an estimated 44.4 million people with dementia worldwide. This number is projected to increase to an estimated 75.6 million in 2030, and 135.5 million in 2050, largely attributable to demographic aging that reflects the successes of improved health care over the last century. Many are now living longer and healthier lives and so the world population has a greater proportion of older people.
There is currently no cure for Alzheimer's disease or for most other causes of dementia. From an anti-aging perspective, at this time it is most essential to ascertain how to prevent the disease from occurring and how to stop its progression. As such, in this article we review recent diagnostic innovations that hold great promise in promoting early detection and prevention of Alzheimer's Disease.

Dementia statistics [Web page]. Alzheimer's Disease International. Accessed 2 Sept. 2014.

Blood Test May Help Assess Memory Loss
Thrombogenic microvesicles are shed by activated platelets in the blood, and higher levels may raise the risk of developing white matter hyperintensities (WMH) in the brain, among postmenopausal women. Mayo Clinic (Minnesota, US) researchers report that they may be an indicator of the risk of developing WMH – small areas of brain damage that have been linked to memory loss. Kejal Kantarci and colleagues analyzed 95 women, average age 53 years, who were a subset of those enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study, in which magnetic resonance imaging (MRI) was used to measure changes in WMH before randomization and at 18, 36, and 48 months afterward. At the study's start, the researchers measured conventional cardiovascular risk factors, carotid intima-media thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and numbers of thrombogenic microvesicles. They correlated those with changes in WMH volume, adjusting for a number of factors. On average across the subjects, the volume of WMH rose by 63 mm3 at 18 months, 122 mm3 at 36 months, and 155 mm3 at 48 months. Whereas only the 36- and 48-month levels were significantly different from baseline, these levels were significantly correlated with the numbers of platelet-derived and total thrombogenic microvesicles observed at baseline, and not with the other measured risk factors. The study authors conclude: "Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in [white matter hyperintensities] suggest that in vivo platelet activation may contribute to a cascade of events leading to development of [white matter hyperintensities] in recently menopausal women."

Raz L, Jayachandran M, Tosakulwong N, et al. Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women.
Neurology. 2013 Feb 13.

New Biomarker of Alzheimer's Disease
Mitochondrial DNA (mtDNA), present in cerebral spinal fluid (CSF), emerges as a novel biomarker of Alzheimer's disease – signaling the disease a decade before symptoms manifest. Ramon Trullas, from the CSIC Institute of Biomedical Research (Spain), and colleagues have discovered that a decrease in the content of mtDNA in CSF may be a preclinical indicator for Alzheimer's disease; furthermore, there may be a directly causative relationship. The team hypothesizes that decreased mtDNA levels in CSF reflect the diminished ability of mitochondria to power the brain's neurons, triggering their death. The decrease in the concentration of mtDNA precedes the appearance of well-known biochemical Alzheimer's biomarkers (the A[beta]1-42, t-tau, and p-tau proteins), suggesting that the pathophysiological process of Alzheimer's disease starts earlier than previously thought. The study authors submit: "These findings support the hypothesis that mtDNA depletion is a characteristic pathophysiological factor of neurodegeneration in [Alzheimer's disease].

Podlesniy P, Figueiro-Silva J, Llado A, et al.  Low CSF concentration of mitochondrial DNA in preclinical Alzheimer's disease.
Ann Neurol. 22 June 2013.

Predictive Blood Test
A blood test, developed and validated by Howard J. Federoff and colleagues from Georgetown University Medical Center (Washington DC, US), may predict with greater than 90% accuracy if a healthy person will develop mild cognitive impairment or Alzheimer's disease within 3 years. The test identifies 10 lipids in the blood that predict disease onset. The researchers examined if the presence of the APOE4 gene, a known risk factor for developing Alzheimer's disease, would contribute to accurate classification of the groups, but found it was not a significant predictive factor in this study. Writing, "This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease," the study authors are optimistic that the test could be ready for use in clinical studies in as few as two years.

Mapstone M, Cheema AK, Fiandaca MS, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nature Medicine, 9 March 2014. Demographics data via James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. Contribution of Alzheimer disease to mortality in the United States.
Neurology. 2014 Mar 5.

DIY Cognitive Screening
A self-administered test may help spot early symptoms of cognitive issues. Researchers at Ohio State University (US) have developed a do-it-yourself test that can help doctors spot early symptoms of cognitive issues in their patients. The Self-Administered Gerocognitive Examination (SAGE test) can also be taken at home by patients, who can then share the results with their physicians to promote early disease detection. Taking less than 15 minutes to complete, Douglas Scharre and colleagues posit that the SAGE test enables doctors to get a baseline of cognitive function in their patients, so they can be followed for a later onset of Alzheimer's disease. As well, the team suggests that the SAGE test could also provide health-care providers and caregivers an earlier indication of life-changing events that could lie ahead. Earlier research by Scharre found that 4 out of 5 people (80%) with mild thinking and memory (cognitive) issues will be detected by this test, and 95% of people without issues will have normal SAGE scores. Observing, "From … 1,047 individuals over age 50 screened with SAGE …cognitive impairment was identified in 28%," the study authors submit: "Community cognitive screening using SAGE was found to be feasible and efficient in diverse settings with both small and large groups."  

Scharre DW, Chang SI, Nagaraja HN, Yager-Schweller J, Murden RA. Community Cognitive Screening Using the Self-Administered Gerocognitive Examination (SAGE).
 J Neuropsychiatry Clin Neurosci. 2014 Jan 13.

Measuring the Aging Brain
Arterial health in the brain is essential for optimal brain aging and may serve a preventive role against Alzheimer's disease and aging-related cognitive decline. Monica Fabiani and colleagues from the University of Illinois (US) devised a novel optical imaging technique to measure pulse pressure of the brain's cortex. The initial results using this new technique find that arterial stiffness is directly correlated with cardiorespiratory fitness: the more fit people are, the more elastic their arteries. Because arterial stiffening is a cause of reduced brain blood flow, stiff arteries can lead to a faster rate of cognitive decline and an increased chance of stroke, especially in older adults. Studying a group of 53 participants, aged 55 to 87 years, via the new optical imaging technique, the study authors report, "Regional pulse transit time predicts specific neuropsychological performance."

Fabiani M, Low KA, Tan CH, et al. Taking the pulse of aging: Mapping pulse pressure and elasticity in cerebral arteries with optical methods.
Psychophysiology. 2014 Aug 6.

There are 7.7 million new cases of dementia each year, implying that there is a new case of dementia somewhere in the world every 4 seconds. Thanks to diagnostic advancements such as those profiled above, scientists have state-of-the-art tools to ascertain how to prevent Alzheimer's disease from occurring and how to stop its progression.

To learn of the latest anti-aging diagnostics technologies that may help with the early detection and prevention of Alzheimer's disease, visit the World Health Network (, the official educational website of the A4M and your one-stop resource for authoritative anti-aging information. Be sure to sign up for the free Longevity Magazine e-journal, your weekly health newsletter featuring wellness, prevention, and biotech advancements in longevity.

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