The relationship between stress and Alzheimer's disease

Abstract

Stress is critically involved in the development and progression of disease. From the stress of undergoing treatments to facing your own mortality, the physiological processes that stress drives have a serious detrimental effect on the ability to heal, cope and maintain a positive quality of life. This is becoming increasingly clear in the case of neurodegenerative diseases. Neurodegenerative diseases involve the devastating loss of cognitive and motor function which is stressful in itself, but can also disrupt neural circuits that mediate stress responses. Disrupting these circuits produces aberrant emotional and aggressive behavior that causes long-term care to be especially difficult. In addition, added stress drives progression of the disease and can exacerbate symptoms. In this review, I describe how neural and endocrine pathways activated by stress interact with ongoing neurodegenerative disease from both a clinical and experimental perspective.

Keywords: Alzheimer's disease; CRF; CRH; Corticosteroids; Cortisol; Stress.

Fig. 1

The Vicious Cycle of Stress. On the right arc of the cycle, elevated stress exacerbates Alzheimer's Disease, causing more rapid development of pathology and loss in cognitive function. On the left arc of the cycle, disease perturbs stress responsive neural circuits, producing neuropsychiatric co-morbidities, including depression, anixety, and aggressive behavior. The HPA axis (center), in which hypothalamic CRF activates pituitary ACTH release and subsequent Cortisol release by the adrenal cortex, has a central role in both the exacerbation of AD by stress, and the stress-related symptoms caused by ongoing neurodegeneration.