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.

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)

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.