Silent Brain Damage in ATTR-CM: Exploring Neurological Impacts

Silent Brain Damage in ATTR-CM
Transthyretin amyloidosis (ATTR) is characterized by the misfolding and accumulation of the transthyretin (TTR) protein, which is responsible for transporting of thyroid hormones and retinol throughout the body. The heart is one of the most common places for TTR to accumulate, causing heart muscles to stiffen and making it difficult to pump blood; this is known as ATTR cardiomyopathy (ATTR-CM).

Patients with ATTR-CM are at high risk of thromboembolic events, including stroke. Similar to the heart, TTR can build up in the central and peripheral nervous systems, particularly in the nerves. Unfortunately, however, we don’t yet fully understand the neurological effects of ATTR-CM.

Exploring Neurological Impacts in ATTR-CM Patients
A recent study examined the cerebral MRI (cMRI) scans of patients with ATTR-CM and no outward neurological symptoms compared to a control group without ATTR but with similar cardiovascular risks. Cardiovascular risks were assessed in each group using the CHA₂DS₂-VASc score for stroke. Both groups underwent imaging, and scans were analyzed blindly for signs of small vessel disease, including silent strokes, cerebral microbleeds, and other markers of brain damage.

Major findings included:

• Increased silent brain damage in ATTR-CM patients: ATTR-CM patients showed significantly more territorial infarcts, cerebral microbleeds, and Virchow-Robin spaces compared to control group. Lacunar lesion presence was also higher in these patients compared to the control group, although not significantly.
• Stroke risk factors as poor predictors of small brain infarcts: CHA₂DS₂-VASc score, atrial fibrillation, anticoagulation therapy, and the interaction term of CHA₂DS₂-VASc score and atrial fibrillation were not correlated with having territorial ischemic lesion or lacunar lesions.

Alarmingly, this study highlights the silent yet notable prevalence of brain damage in ATTR-CM patients, which can occur with no apparent symptoms. This raises concerns because such damage can contribute to long-term cognitive decline or other complications.

Because traditional stroke risk predictors may not correlate with the risk of cerebral small vessel disease, we can implement preventative measures to proactively monitor cognitive plasticity of patients with ATTR-CM. These may include early detection and monitoring using cMRI as well as lowering the threshold for prescribing anticoagulation therapy to prevent clots.

References:
Haider, L., Schrutka, L., Tommasino, E., Avanzini, N., Hauck, S., Nowak, N.,…Thurnher, M. (2024). Cerebrovascular Involvement in Transthyretin Amyloid Cardiomyopathy. J Clin Med, 13(15). https://doi.org/10.3390/jcm13154474

Taipa, R., Sousa, L., Pinto, M., Reis, I., Rodrigues, A., Oliveira, P.,…Coelho, T. (2023). Neuropathology of central nervous system involvement in TTR amyloidosis. Acta Neuropathol, 145(1), 113-126. https://doi.org/10.1007/s00401-022-02501-9