HoldsUp

Axel Montagne

UK Dementia Research Institute at the University of Edinburgh Centre for Clinical Brain Sciences

Axel Montagne, PhD, is a Chancellor's Fellow and group leader at the UK Dementia Research Institute at the University of Edinburgh Centre for Clinical Brain Sciences. His research focuses on the role of brain vasculature and blood-brain barrier dysfunction in the early stages of dementia and age-related cognitive decline. His published studies cover topics including glial-vascular interactions, pericytes, transcriptomics of brain vascular cells, cerebral small vessel disease, and neurodegenerative mechanisms in Alzheimer's disease.

62 claims checked on air: 5 context 5 contradicted 3 overstated 43 supported 6 unverified

What they said on air - context

14 citing their own research

0:01:05needs contextmoderateAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Lack of exercise accelerates cognitive decline, particularly in individuals with major genetic risk factors.

"You're gonna be prone to go to cognitive decline because let's say you have a major genetic risk, but if on top of that you don't exercise you're gonna accelerate as we know from studies." (said at 0:01:05)

The claim is partially supported, but requires qualification regarding the interaction between physical activity and genetic risk. Physical inactivity and lack of exercise are well-established modifiable risk factors for accelerated cognitive decline and dementia. However, whether a lack of exercise accelerates cognitive decline *specifically more* in individuals carrying major genetic risk factors (such as the APOE ε4 allele) remains mixed and non-definitive across published studies. While some longitudinal observational studies (such as the Nurses' Health Study) suggest that physical activity may offer stronger protective benefits—or that physical inactivity confers greater risk—in APOE ε4 carriers, large systematic umbrella reviews and major multi-year prospective cohort studies show that the protective effect of physical activity against cognitive decline occurs regardless of APOE status, with no statistically significant interaction between lifestyle factors and APOE genotype. Therefore, while lack of exercise contributes to cognitive decline, evidence for a strong synergistic acceleration unique to genetic risk carriers is inconsistent.

0:32:19needs contextmoderateAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Small vessel disease is a common cause of stroke and develops independently of amyloid accumulation.

"So these are the features of small vessel disease, and small vessel disease is also the common cause of stroke... But that's a disease that is independent of amyloid. That's the big difference, obviously, from Alzheimer's disease." (said at 0:32:19)

The claim is roughly accurate but requires qualification. Non-amyloid small vessel arteriopathies (such as deep perforator arteriopathy or arteriolosclerosis) represent a leading cause of stroke—particularly lacunar ischemic strokes and hypertensive intracerebral hemorrhages—and develop independently of amyloid-beta accumulation, unlike Alzheimer's disease. However, cerebral small vessel disease (CSVD) is a broad umbrella term that also includes cerebral amyloid angiopathy (CAA), a distinct CSVD subtype defined specifically by the deposition of amyloid-beta within small cerebral vessels.

1:05:45needs contextvery lowAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Following an ischemic stroke, there is a biphasic breakdown of the blood-brain barrier at 2 hours and 3 days that correlates with two peaks of MMP-9 expression.

"when you have an ischemic stroke, you have a second breakdown a few days later, so it's a what we call biphasic breakdown of the barrier: two hours and three days. And same thing for MMP-9, two peaks of the expression." (said at 1:05:45)

Preclinical models of ischemic stroke and reperfusion injury demonstrate a well-established biphasic opening of the blood-brain barrier (BBB), characterized by an initial transient opening occurring within several hours post-ischemia and a secondary, more severe opening occurring 24 to 72 hours (1 to 3 days) later. However, in the classic neurovascular cascade, the early phase is driven primarily by the activation of constitutive gelatinase A (MMP-2), whereas gelatinase B (MMP-9) and MMP-3 are induced and peak during the delayed phase (24–72 hours). Although biphasic expression of MMP-9 specifically has been observed in certain rodent models under high oxidative stress (such as SOD2-deficient mice), the standard biphasic BBB opening reflects sequential involvement of MMP-2 (early) and MMP-9 (late).

1:14:25needs contextvery lowAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Perivascular spaces surrounding cerebral arteries enlarge during sleep.

"because at the arterial level you have the perivascular space, which is enlarged when you sleep, it has been shown." (said at 1:14:25)

The speaker appears to conflate the periarterial perivascular space with the brain's interstitial (extracellular) space. The seminal study by Xie et al. (2013) demonstrated in mice that natural sleep and anesthesia cause a ~60% expansion of the interstitial space volume fraction (measured via tetramethylammonium iontophoresis and two-photon imaging), which drastically increases convective cerebrospinal fluid (CSF) influx along periarterial routes and enhances metabolite clearance. While periarterial perivascular spaces serve as the major conduit for CSF entry during sleep-associated glymphatic influx, the physiologically demonstrated expansion occurs in the interstitial space of the parenchyma.

1:19:19needs contextlowAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Blood-brain barrier leakage in hypothalamic regions controlling feeding can trigger obesity rather than obesity causing the leakage.

"William Banks, one of the—if not the one—the most highly cited researcher when it comes to blood-brain barrier, I think he is in California. He also wrote a recent review that blood-brain barrier leakage will trigger obesity and not the other way around as we age." (said at 1:19:19)

The relationship between blood-brain barrier (BBB) dysfunction and obesity is bidirectional and multifaceted, rather than a simple unidirectional model where leakage triggers obesity instead of obesity causing leakage. Research by Dr. William Banks and colleagues shows that diet-induced obesity and metabolic dysfunction lead to oxidative stress and BBB leakage (hyperpermeability) in areas including the hypothalamus and hippocampus. Concurrently, specific alterations at the BBB—most notably impaired receptor-mediated transport of satiety hormones like leptin across the barrier—can promote central leptin resistance, hyperphagia, and subsequent weight gain. Thus, while functional transport deficits at the BBB contribute to obesity, obesity itself is a primary cause of physical BBB leakage.

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