Early Parental Death and Late-Life Dementia Risk - Findings from the Cache County Study
Age and Aging
Oxford University Press
SIR—Dementia is a major public health problem. Alzheimer's disease (AD) comprises the majority of dementia cases, and while the causes are still largely unknown, epidemiological studies are investigating a broad array of both genetic and environmental risk factors. Plausible aetiological mechanisms include lipid metabolism, inflammation and glucose regulation. Emerging biological evidence suggests that another potential mechanism for increased AD risk is neuronal death through the lifelong cumulative effect of stress reactivity and recovery . Repeated stress causes damage to the CA3 region of the hippocampus via glucocorticoids and excitatory amino acid neurotransmitters released during and immediately after stress. Long-term, chronic stress over many years appears to continue the process and result in neuronal death in the hippocampus . Physiological stress responses may also affect health by modulating the rate of cellular ageing via higher oxidative stress, lower telomerase activity and shorter telomere length, all indicators of cell longevity  with evidence that neurodegenerative changes may begin decades before clinical manifestation [4, 5].
Norton MC, Ostbye T, Smith KR, Munger RG, Tschanz JT. Early parental death and Late-life dementia risk. Findings from the Cache County Study. Age and Aging 2009;1-4.