A Neurologist on Vascular Dementia, Explained

Vascular dementia is caused by damage to the brain’s blood vessels, and it’s the second most common form of dementia after Alzheimer’s disease. Often triggered by strokes, high blood pressure, or diabetes, vascular dementia can impair thinking, memory, balance, and coordination.

UCLA vascular neurologist and neuroscientist Dr. Jason Hinman diagnoses and treats patients with vascular dementia, and beyond that, he’s a researcher. His work explores the molecular pathways that connect stroke and cognitive decline. His findings are helping inform the quest for new diagnostic tools and treatments. 

In this interview with Being Patient’s Mark Niu, Hinman explains the differences between vascular dementia and Alzheimer’s, particularly when it comes to symptoms and progression, and why vascular dementia often coexists with other types of dementia. 

He also digs into the importance of midlife lifestyle changes and managing modifiable risk factors like hypertension and diabetes — and he shares why he’s hopeful about new research into treatments, including GLP-1 drugs (like Ozempic and Wegovy), anti-inflammatory therapies, and even senolytics (a class of drugs designed to slow biological aging).

Being Patient: Tell us, in simplest terms, what is vascular dementia?

Dr. Jason Hinman: Vascular dementia is the second most common cause of dementia worldwide. It accounts for about 20 percent of all cases of dementia. The diagnostic criteria include the development of cognitive symptoms and often some minor systemic symptoms that affect a patient neurologically. We use imaging to distinguish between the various subtypes.

Being Patient: What are the key signs and symptoms that help distinguish vascular dementia from Alzheimer’s or other types of dementia?

Hinman: Patients who present with vascular dementia most commonly have a presentation that’s a little atypical from classic Alzheimer’s disease. In classic Alzheimer’s disease, patients frequently present with what we call amnestic symptoms — difficulties remembering words, faces, [and] particular events in the recent past.

Patients with vascular dementia typically have similar problems but more frequently have difficulties in executive function. They have trouble with sequencing — remembering how to do one thing, then the next. This often manifests in functional deficits, commonly at work, if patients are still of working age. That’s one cognitive feature that can differentiate classic Alzheimer’s disease from vascular dementia.

A second issue is that vascular dementia tends to affect a wide area of the brain, particularly the brain connections. This manifests not only in cognitive deficits but also in mobility and coordination. Patients often have deficits in balance, and the speed of their ability to [perform] neurologic functions. We see slowing of reaction time, balance, and coordination. This can also present difficulties in gait — they have trouble walking, [and] the speed of walking may slow.

Those are the two broad areas where patients may have deficits that help us be clearer about the type of dementia they have.

Being Patient:  What diagnostic tools do you rely on most to diagnose vascular dementia?

Hinman: Everything starts clinically. You do a cognitive assessment. Sometimes, the tools we use for measuring cognitive function in the outpatient clinic can give a clue. If it’s more of an executive function than a pure amnestic memory component, that can be a clue. The neurologic exam can also clue you into gait, balance, and reaction time. For more advanced diagnostic tools, the standard is to use a brain MRI scan to distinguish hallmark features of vascular dementia compared to Alzheimer’s disease.

Being Patient: Are there certain biomarkers you can detect for early detection?

Hinman: There are imaging hallmarks — that we would also use the term biomarkers for — that help distinguish. These include changes on particular MRI sequences, often referred to in radiographic imaging reports [as] white matter hyperintensities or microvascular ischemic disease. These are lesions in deep parts of the brain that are generally due to problems in smaller blood vessels — a hallmark feature of vascular dementia.

[Another big category] is strokes. Strokes can be clinically recognizable by the patients, and they get care in the hospital. These events can also accumulate over time to lead to vascular dementia.

Being Patient: What are the most common underlying causes of vascular dementia?

Hinman: About 40 percent of all cases of dementia are due to modifiable risk factors. These include a Western diet rich in saturated fats, lack of exercise, poor sleep, and vascular risk conditions like high blood pressure, diabetes, and hyperlipidemia.

What’s unique about the risk factors is, they increase circulating levels of inflammatory indicators. We might use a broad basket of neuroinflammation to talk about these risk factors. There’s now an emerging set of biomarkers that can be measured in the bloodstream that can indicate an increased risk for vascular dementia.

Inflammation is not the only area where this manifests; there also appear to be deficits in angiogenesis — the biological process that regulates blood vessel development and maintenance. These two things probably coordinate together to damage small blood vessels, and that is a predominant precipitate of vascular dementia.

“About 40 percent of all cases of dementia
are due to modifiable risk factors.”

Being Patient: Are there many types of vascular dementia, or just a few kinds based on where the strokes happen? Are there a range of locations, or is it narrowed down to a few different areas?

Hinman:Yes. [There are] two subtypes of vascular dementia. [One] would be the kind that is due to chronic, risk factor-induced damage to the smaller blood vessels in the brain. This is an insidious form, difficult to pick up clinically unless patients have symptoms. It’s an area where we need new and emerging biomarkers.

The second subtype is that due to a larger vessel stroke that might affect strategic areas of the brain. Prior studies suggest that injury to the left frontal lobe [is commonly] associated with an increased risk for vascular dementia.

We have a large ongoing study called the Discovery Network Study, which is organized across a variety of stroke centers in the U.S. [The study recruits] patients across a variety of racial and ethnic subgroups with a variety of risk factor profiles — looking at if [the patient] comes in with that stroke and is cognitively intact, what are the things that lead to an increased risk of dementia. In some populations, prior data suggests that risk can be as high as 40 percent. We’re trying to understand where in the brain those lesions are most likely to affect stroke. We’re using high-resolution imaging, genetics, and blood biomarkers to predict the risk of this subtype.

Being Patient:  If someone has a stroke, do you know the chances of developing dementia within a certain time?

Hinman: The five-year risk can be as high as 50 percent. This is data generally from the U.K. The data is strong, but it lacks details [such as] where in the brain the stroke occurred [and] what the characteristics of that particular patient are. It does depend on how severe the stroke was. Also, how old you are. As we get older, we lack the resiliency to recover from [a stroke], so if that occurs later in life, the risk of developing substantive cognitive impairment is markedly higher.

Being Patient: Is there any evidence that lifestyle changes alone can prevent or delay vascular dementia?

Hinman: Yes, I believe there’s strong data. Vascular risk factors as early as midlife can cause an increased risk for late-life cognitive impairment and dementia. It’s important to [manage] blood pressure, blood sugar, cholesterol, and physical activity as early as your 40s to prevent late-life cognitive impairment. The more patients that recognize these as key risk factors, the more aggressive we can be. We hope to provide biomarker tools so patients get real-time feedback.

In terms of actual evidence [that] we can reduce the rate of dementia if we make those changes, it is just now emerging. At the Alzheimer’s Association International Conference in Toronto, data from the POINTER study [showed lifestyle changes can impact dementia risk]. We need to explore how to implement this for patients.

“ Vascular risk factors as early as midlife can cause an increased risk for late-life cognitive impairment and dementia.”

Being Patient:  What treatments are currently available for managing vascular dementia? Do any medications help slow its progression?

Hinman: First, we address all the risk factors. Is blood pressure under optimal control? Is diabetes under optimal control? Is cholesterol treatment optimized? If all three are relevant, we address them to prevent things from getting worse, ideally.

Second, we discuss with patients the evidence for using common symptomatic treatment for dementia. There is reasonable evidence that acetylcholinesterase inhibitors, which are FDA-approved for the treatment of Alzheimer’s dementia, have good off-label evidence that they can partially mediate the cognitive symptoms associated with vascular dementia and slow the rate at which those symptoms manifest. 

Another related agent that’s been used a lot in Europe is memantine, another drug FDA-approved for Alzheimer’s disease, but off-label and used in cases of vascular dementia. I use those medications frequently in patients who are overtly symptomatic from a cognitive standpoint.

We don’t right now have anything outside of the risk factor modulation that can fix or repair the injury that’s occurred to the brain. But there are some exciting ideas out there and interest in developing clinical trials that will address those underlying disease pathways.

Being Patient: You teased that they may be working on some cutting-edge treatments. What types of approaches are those?

Hinman: There’s emerging data on the effect of GLP-1 agonists. The so-called weight-loss drugs also affect a lot of cardiovascular and cerebrovascular risk conditions. I think we’re going to see that those drugs will have partial efficacy in reducing all forms of dementia — in particular, vascular dementia — because of their effect on core risk factors for the disease.

Whether there will be a definitive clinical trial is unclear because the drugs are already approved. But I think we’ll see emerging data that will provide strong evidence that these are reasonable agents to help reduce underlying risk and progression.

The second area is inflammation. The inflammatory condition that results from these risk factors directly affects brain blood vessels. In turn, that affects how the brain responds to inflammation. That’s an attractive therapeutic target we can start to modulate.

[The third area] is thinking about ways to promote new blood vessel growth — modulating the angiogenesis biologic pathway. Smaller blood vessels display age-related phenomena. They may be failing to sprout and grow new blood vessels as time goes on.

I would follow closely the area where we’ve developed drugs that can modulate the aging process. One place they may be most relevant is in helping to maintain blood vessel health and integrity. This is a class of drugs referred to as senolytics, or drugs that stop aging. I think they have an attractive possibility for vascular dementia and overall brain health.

Being Patient: How does vascular dementia typically progress over time, and what should families expect in terms of disease trajectory?

Hinman: Vascular dementia tends to have step-offs, where patients are doing well, coping, demonstrating resiliency, and then suddenly there’s a significant change. Then they may stay at that plateau for 6 to 12 months, and then there’s another step-off and another noticeable decline.

Often, those declines are related to strategically located strokes deep in the brain. That takes away resiliency dramatically, as opposed to insidiously. Patients and caregivers will experience a slower rate of progression but with noticeable drop-offs in functionality. That can be difficult to deal with.

Being Patient: How often do you see vascular dementia in combination with Alzheimer’s disease, and does that affect the treatment?

Hinman: At the top of the show, we talked about vascular dementia being the second most common and Alzheimer’s being the most common [form of dementia]. But there’s not a clear delineation between these pathologies. Most patients with Alzheimer’s disease will have a component of vascular injury to the brain. At least half of patients will have mixed pathology.

Right now, we’re trying to figure out how much that impacts whether new FDA treatments for Alzheimer’s disease are likely to be more or less effective in that population. We’re participating in a large study to develop specific biomarkers so we can distinguish those two things.

We have good new tools for Alzheimer’s disease to measure brain amyloid, and we have treatments to clear it. We don’t yet have those tools for the other pathologies that are ready clinically. I think in the next couple of years, those things will be available. It will be important, and we’ll learn a lot about who’s likely to respond to particular types of treatment.