The Impact of Excessive Dietary Sodium on Brain Health

Sporadic cerebral small vessel disease (CSVD) is not only the most common subtype of vascular dementia, in recent multi-center study showed that sporadic CSVD harbors in a third of Alzheimer's disease (AD) patients in 9 Asian regions. The CSVD increases the severity of cognitive impairment in these patients and has an etiological contribution to the development of AD. Studies demonstrated that CSVD is more prevalent in Chinese than in Australians and this association was independent of traditional vascular risk factors (e.g. hypertension). Other factors such as lifestyle, environmental or genetic factors may explain this difference. Although hypertension is an important cause for CSVD, it only accounts for a small proportion of the variance in CSVD. Irrespective of the cause, it is currently believed that endothelial dysfunction of CSVD is the key pathophysiological mechanism of CSVD. Having an effective treatment of CSVD will have an enormous impact on the prevention of dementia.

Excessive dietary sodium is an established risk factor for cardiovascular diseases, including stroke. It is traditionally linked to its effects in raising blood pressure. The Department of Health advocated reducing salt intake for the prevention of hypertension, coronary heart disease, and stroke.

However, recent epidemiological studies suggest that it may have a direct effect on cardiovascular diseases independent of blood pressure. A recent animal study showed that excessive dietary sodium-induced cerebral endothelial dysfunction, resulting in cognitive impairment. Interestingly, endothelial dysfunction was related to an adaptive immune response in the gut. A clinical study conducted in the United Kingdom suggested excessive dietary sodium intake may promote CSVD

A clinical study conducted in the United Kingdom suggested excessive dietary sodium intake may promote CSVD by increasing WMH volume in the brain, independent of its effects on blood pressure. Notably, a few animal studies showed that the association between high dietary sodium and worse cognitive function in the absence of blood pressure changes. This pinpoints the important role of dietary sodium as an independent contributor to brain health and cognition.

This study aims to assess the association between dietary sodium, neuroimaging measures, and cognition in cerebral small vessel disease and controls during the 18-month follow-up.

This study hypothesis that high dietary sodium is associated with CSVD-related neuroimaging measures such as reduced white matter hyperintensities, total brain volume, and white matter structural integrity. The second hypothesis is that high dietary sodium is associated with worse cognitive function. These associations may be more prominent in the CSVD group compared to the control group and is independent of blood pressure.

Subjects with severe CSVD (n =110) and healthy controls (n =110) will be recruited.

2 trials of 24 hour urine will be collected at baseline visit and 2 trials of 24 hour urine will be collected at 18 months.

Clinical assessment (e.g. mood, cognition, physical activities, gait etc.) will be assessed at baseline and 18 months.

2 trials of Brain MRI will be conducted at baseline and 18 month visit

Eligibility Criteria:
Inclusion Criteria:

* Chinese ethnicity,
* age between 55 and 80-year-old, and
* a primary language of Cantonese.
* Extra inclusion criteria for CSVD group:

  1. Age-Related White Matter Change (ARWMC) Scale of 2 or early 3 in FLAIR MRI;
  2. Modified Functional Ambulation Classification 5 or above;
  3. Montreal Cognitive Assessment (MoCA) score \< 25;

Exclusion Criteria:

* Hypernatremia (Na \>146mmol/L) or hyponatremia (Na \<134 mmol/L) from screening blood test;
* With sodium supplement;
* Renal failure (stage 4 \& 5) with glomerular filtration rate \< 29;
* performed cardiac surgery or neurosurgery, with cardiac failure;
* Had major psychiatric diseases
* Contraindications for MRI.
* Dementia or MoCA score lower than 2nd percentile of the age and education adjusted cutoff ;
* Cerebral white matter changes unrelated to neurodegenerative, e.g. CADASIL, X-linked adrenoleukodystrophy, metabolic diseases, multiple sclerosis, etc.\|
* Contraindication to proposed imaging, e.g. chronic kidney disease (KDNIGO) stage 4 or above, acute kidney injury, hypersensitivity to gadolinium-based contrast, non-MRI conditional implants or prosthesis
* Medical condition that would not allow the patient to adhere to the protocol or complete the study.;
* Patient with established neurodegenerative disorders (e.g. Parkinson's Disease, Alzheimer's Disease, etc.);
* Pregnancy.