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Brainlift-Program_Vascular-Alzheimers

8 Signs of Vascular Alzheimer’s Disease

Trouble with Episodic Memory

Difficulty remembering specific events in life.

Trouble with Working Memory

Difficulty remembering information long enough to be able to use it.

Trouble with Perceptual Speed Scores

Loss of ability to quickly and accurately interpret information and respond.

ApoE Genetic Risk

One copy of ApoE4 gives you a 30% chance of getting AD. Two copies give you a 50% chance.

Elevated Inflammatory Markers

High levels of CRP and Homocysteine.

Suboptimal Cholesterol

High/low amounts, sizes, and ratios of cholesterol.

Insulin Resistance

Elevated insulin levels indicating some degree of insulin resistance.

Tiny Strokes

MRIs show evidence of tiny (asymptomatic) strokes in the brain.

Subtype No. 4

Vascular

Alzheimer’s Disease

The vascular subtype of Alzheimer’s disease (AD) is distinct from the other subtypes, though there are some overlapping features, including some underlying causes and symptoms.

PLAQUE & TANGLE

Vascular Dementia vs. Vascular Alzheimer’s

How is the vascular subtype of Alzheimer’s different from vascular dementia? This can get quite confusing, but ultimately one of the main differences is that people who suffer from the vascular subtype of AD still show the Alzheimer’s related beta-amyloid plaques and tau tangles, whereas people suffering from vascular dementia do not.

Research has demonstrated that vascular disease is associated with an increased risk of degenerative Alzheimer (plaque and tangle) pathology, either by increasing its rate of formation or reducing elimination from the brain, or a mixture of the two. (1)

VASCULAR

Risk Factors

The risk factors for this subtype are similar to those for heart disease (aka cardiovascular disease). They include increasing age, hypertension, smoking, suboptimal cholesterol levels (too high, too low, abnormally small cholesterol particles, etc), diabetes, and metabolic syndrome (abdominal obesity, low HDL, high triglycerides, high blood sugar, and high blood pressure). (2)

Interestingly, obesity (BMI of 30 or higher) is independently tied to poor overall blood flow in the brain, including in areas related to memory such as the hippocampus. (3)

“The tiny strokes associated with the brain damage that leads to the vascular subtype of Alzheimer’s disease are like branches in a tree that slowly die off. Our goal is to restore life to the brain by stopping new branches from dying and encouraging new growth to replace what’s been lost.”

Dr. Scott Noorda, DO

Family Physician, Precision Medicine

Signs + Symptoms

of VASCULAR ALZHEIMER’S DISEASE

The risk for this subtype increases with age, as is the case with cardiovascular disease, with symptoms typically starting in the mid-sixties to early seventies. The initial symptoms of the vascular subtype of AD highly depend on the specific area(s) of the brain with the greatest vascular compromise. For example, if the language areas of the brain have the highest concentration of tiny strokes or the worst blood flow then the first symptoms might be a harder time with reading comprehension, or with effectively expressing oneself.

Studies have shown that episodic memory (remembering specific events in life), working memory (remembering information long enough to be able to use it), and perceptual speed scores (the ability to quickly and accurately interpret information and respond accordingly) tend to fall more rapidly among older adults who have the highest cardiovascular risk. The same is most often the case with the vascular subtype of AD.

In other words, the symptoms typically start out more concentrated, such as only affecting one’s ability to remember names, or ability to make quick decisions while driving, but can become widespread as the damage from both vascular compromise and AD pathology accumulate over time.

Genetic Factors

of VASCULAR ALZHEIMER’S DISEASE

The most well known genetic risk factor for AD is the ApoE gene, specifically with the ε4 allele (ApoE-4). Briefly, alleles are variants of a gene controlling the same trait and occupying the same specific region on a chromosome. We each inherit one allele from each parent, and the combination of those alleles is what creates our unique characteristics.

The most common allele is ε3 (ApoE-3), which is found in more than half of the general population and has a lower risk for AD. This risk goes up if you inherit one copy of ApoE-4 from a parent, and the highest risk for dementia comes from receiving copies of the ε4 allele from both parents, written as ApoE4,4.

In the general population, low plasma concentrations of ApoE protein are associated with higher risk of dementia and Alzheimer’s disease. This is independent of ε2/ε3/ε4 ApoE genotype, though the ε4 allele is associated with a lower total ApoE concentration. (4)

There is also an interesting interplay between total ApoE levels, a molecule called APOC3, and HDL (good) cholesterol. Studies have shown that the presence of a molecule called APOC3 appears to modulate the association between ApOE levels in HDL and dementia. Higher ApoE levels in HDL that lacked APOC3 were tied to better cognitive function and lower dementia risk. (4)

Lab Indications

of VASCULAR ALZHEIMER’S DISEASE

Different subtypes can’t always easily be distinguished by lab testing, but there are some unique findings in the vascular subtype that are worth mentioning.

Abnormal lab findings in the vascular subtype of AD can include some or all of the following:

  • Elevated Homocysteine (>8 umol/L) – causes inflammation in the wall of the blood vessels and has been associated with brain atrophy when elevated.
  • Elevated HS CRP or High Sensitivity C-Reactive Protein (>1 mg/L) – marker of both generalized as well as cardiac / blood vessel specific inflammation.
  • Elevated fasting glucose (>90 mg/dL)
  • Elevated average glucose, aka hemoglobin A1C (>5.6%).
  • Elevated insulin levels are frequently seen, and can sometimes arise as an earlier warning sign before significant glucose elevations show up on the labs.
    • Fasting insulin levels >9 uIU/mL
    • c-peptide (provides some idea of a longer term, more average insulin) levels >/= 2 ng/mL
  • Suboptimal Cholesterol Amounts & Ratios
    • Elevated Triglycerides (>90 mg/dL)
    • Low HDL (i.e. Good) Cholesterol (<50 mg/dL for men, <60 mg/dL for women)
    • Low HDL to Triglyceride Ratio (<0.7 or 70%)
    • Elevated LDL Cholesterol (In general goal is <130). This depends on the size/type of LDL (not all is bad). High LDL particle number = more small, dense LDL particles (>1138 nmol/L)
    • Small LDL peak size (<222 angstrom) Elevated apolipoprotein B (>90 mg/dL)
    • Elevated lipoprotein a (>75 nmol/L)

Target levels for these nutrients and hormones aren’t always the levels shown as normal by different lab companies. Discuss them with a practitioner trained in optimizing and personalizing these lab findings.

MRIs typically will show evidence of tiny little strokes in the brain, though most people don’t ever remember having symptoms of a stroke. High cardiovascular risk individuals also had smaller hippocampus, gray matter, and total brain volumes and more white matter damage, often with wording such as “white matter lesions” or “lacunar infarcts” in the radiologist’s interpretation. (3)

Another possible way to assess the extent of blood vessel related risk is to have a Coronary Calcium Scan performed. A Coronary Calcium Scan is a specialized x-ray that looks for calcified plaque inside the arteries of the heart. The result of the test is usually given as a number called an Agatston score. The score reflects both the total area of calcium deposits and the density of the calcium. (5)

  • 0 = no calcium seen in the heart = low chance of developing a heart attack in the future
  • When calcium is present, the higher the score, the higher your risk of heart disease.
  • 100-300 = moderate plaque deposits = relatively high risk of heart attack or other heart disease in the next 3-5 years.
  • >300 = very high risk

This isn’t a critical test to have performed in order to determine if you have or are at risk of vascular subtype of AD, but can provide additional supporting evidence as well as an assessment of the severity of risk.

Alzheimer’s Prevention Articles

REFERENCES
1.  T O’Brien, J., & Markus, H. S. (2014). Vascular risk factors and Alzheimer’s disease.
2.  Yaffe, K., Bahorik, A. L., Hoang, T. D., Forrester, S., Jacobs, D. R., Lewis, C. E., … & Reis, J. P. (2020). Cardiovascular risk factors and accelerated cognitive decline in midlife: The CARDIA Study. Neurology, 95(7), e839-e846.Amen, D. G., Wu, J., George, N., & Newberg, A. (2020). Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults. Journal of Alzheimer’s Disease, (Preprint), 1-7.
3.  Song, R., Xu, H., Dintica, C. S., Pan, K. Y., Qi, X., Buchman, A. S., … & Xu, W. (2020). Associations between cardiovascular risk, structural brain changes, and cognitive decline. Journal of the American College of Cardiology, 75(20), 2525-2534.
4.  Koch, M., DeKosky, S. T., Goodman, M., Sun, J., Furtado, J. D., Fitzpatrick, A. L., … & Mukamal, K. J. (2020). Association of Apolipoprotein E in Lipoprotein Subspecies With Risk of Dementia. JAMA network open, 3(7), e209250-e209250.
5.  Bredesen, D. (2017). The End of Alzheimer’s: The first program to prevent and reverse cognitive decline. Penguin. pp. 104-108.
6.  Mayo Foundation for Medical Education and Research (MFMER). (2018). Heart scan (coronary calcium scan). Mayoclinic.Org. https://www.mayoclinic.org/tests-procedures/heart-scan/about/pac-20384686#:~:text=A%20score%20of%20zero%20means,300%20means%20moderate%20plaque%20deposits.