The Unraveling: Cardiac and Musculoskeletal Defects and their Role in Common Alzheimer disease Morbidity and Mortality.

Abstract Alzheimer disease (AD), characterized by deterioration of cognitive capabilities, is prevalent among 44 million people worldwide. Beyond memory deficits, the most common AD co-morbidities include swallowing defects (muscle), fractures (bone, muscle), and heart failure. The underlying causes of these co-morbidities and their role in AD pathophysiology are currently unknown. This review is the first to summarize the emerging picture of the cardiac and musculoskeletal deficits in human AD. We present the involvement of the heart, characterized by diastolic heart failure, the presence of amyloid deposits, and electrophysiological changes compared to age-matched controls. The characteristic musculoskeletal defects in AD come from recent clinical studies and include potential underlying mechanisms (bone) in animal models. These studies detail a primary muscle weakness (without a loss of muscle mass) in patients with mild cognitive impairment, with progression of cognitive impairment to AD associating with ongoing muscle weakness AND the onset of muscle atrophy. We conclude by reviewing the loss of bone density in AD patients, paralleling their increase in fracture and fall risk is specific populations. These studies paint broad AD as a systemic disease in broad strokes, which may help elucidate AD pathophysiology and to allow new ways to think about therapeutic intervention, diagnostic biomarkers, and the pathogenesis of this multi-disciplinary disease.