Cardiac Abnormalities in Alzheimer Disease: Clinical Relevance Beyond Pathophysiological Rationale and Instrumental Findings?

ABSTRACT

OBJECTIVES: This case control study sought to assess the presence and characteristics of cardiac abnormalities in patients with Alzheimer disease (AD). BACKGROUND: Protein misfolding is involved in the pathophysiology of neurodegenerative disorders such as AD. Recently, amyloid-beta (Aß) aggregates were identified within the cardiomyocytes and interstitium of patients with AD, suggesting that Aß oligomers may reach and damage the heart. METHODS: The authors studied 32 patients with AD and 34 controls matched by age and sex, all of whom were free from cardiac or systemic diseases. A clinical evaluation, an electrocardiogram, and an echocardiogram were performed in all subjects. Furthermore, patients with AD underwent genetic analyses (of the PSEN1, PSEN2, APP, and APOE genes). RESULTS: Compared to the control group, patients with AD had a higher prevalence of low-voltage electrocardiographic QRS complexes (28% vs. 3%, respectively; p = 0.004), a lower voltage/mass ratio (p = 0.05), a greater echocardiographic interventricular septum (10.1 ± 1.3 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.01), a greater maximum wall thickness (10.8 ± 1.7 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.0001), and a 2-fold higher prevalence of diastolic dysfunction (70% vs. 35%, respectively; p = 0.007). Symptoms and signs of heart failure were absent in all patients with AD. CONCLUSIONS: This study shows that electrocardiographic and echocardiographic abnormalities, including diastolic dysfunction, are present in patients with AD and that these studies reproduce the pattern of cardiac amyloidosis. These findings suggest that, in AD, there may be subclinical cardiac involvement likely associated with Aß amyloid deposition. The clinical relevance of these cardiac abnormalities should be evaluated in larger prospective studies.