Table 1.

Summary of the key findings reported in this review

Disease determinant	Notable feature	Key findings	Ref
Reduced cerebral perfusion	Oxidative stress	• Hypoxia-induced cellular respiration exhaustion and increased ROS production, promoting cell, and BBB injury	[21–23]
		• Worsened by Aβ build-up and consequent mitochondrial dysfunction	[24–26]
	Aβ accumulation	• Reduced Aβ clearance via BBB, interstitial bulk flow, and/or meningeal lymphatic impairment	[27, 28]
		• Reduced Aβ clearance via BBB, interstitial bulk flow, and/or meningeal lymphatic impairment	[29–33]
	Inflammation	• Reduced microglial presence and functioning around Aβ plaques, impairing Aβ internalization and clearance	[34]
Cardiovascular changes	Diastolic dysfunction	• Preserved EF accompanied by high filling pressures, weakened myocardial contractility, reduced peripheral vasodilation, diminished HR response, and less organ perfusion	[35–48]
		• Retrospectively, HFpEF and LV hypertrophy were more likely to be seen in AD patients	[6]
	Arterial stiffness, increased central pulsatility	• Associated with decreased peripheral BF, central Aβ accumulation, BBB injury, cerebrovascular compromise, and brain hypoperfusion	[49–51]
Genetic variants	Presenilin (PSEN) -1 and − 2	• Same variants associated with both early-onset AD and sporadic iDCM	[4]
		• Promoter-specific variants have been observed in iDCM but not yet AD	[4]
Protein aggregation	Brain deposition	• AD aggregates composed of Aβ, tau, metal ions, and chaperones	[52]
		• Cofilin rods implicated in AD neuritis	[53]
	Heart deposition	• Aggregates have been identified in atrial fibrillation, cardiac amyloidosis, and cardiomyopathies—notably, cofilin was isolated from iDCM aggregates	[4, 6, 54]
		• Aβ and PAO deposits seen in AD patients	[7•]
Systemic alterations	Peripheral Aβ accumulation	• Aβ peripheral clearance impaired by decreased scavenger receptors, less proteolytic enzymes, and liver/kidney malfunctioning	[55–58]
		• BBB damage promotes Aβ release into the periphery and potential seeding to other organs	[27, 59]
	Peripheral Aβ Production	• Promotes central Aβ deposition and associated inflammation	[60–64]
	Exosome trafficking	• Help carry Aβ locally and systemically following Aβ endocytosis or APP cleavage	[65–67]
		• Bring MiR-1 from ischemic myocardium to hippocampus, inducing microtubule damage	[68•]