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Early Warnings of Dementia and Depression

Early Warnings of Dementia and Depression

  • Three recent studies reveal that elevated brain levels of amyloid appear to increase the risk of cognitive decline; biomarkers in saliva may help identify early Alzheimer disease; and both peripheral and cerebral microvascular dysfunction are associated with higher odds of late-life depression.[1-3] Scroll through the slides for the latest findings and take-home messages.

  • 1. Patients With Elevated Brain Amyloid Levels May Have a Higher Likelihood of Cognitive Decline Than Those With Normal Levels: A prospective cohort included 445 cognitively normal individuals (mean age, 74 years) who were observed for a median of 3.1 years (maximum follow-up of 10.3 years) as part of the Alzheimer’s Disease Neuroimaging Initiative. Participants with elevated brain amyloid levels had worse average scores at 4 years on measures of cognitive function than those who had normal amyloid levels.[1]

    “The study characterizes change on a cognitive composite outcome designed for pre-symptomatic Alzheimer’s and biomarkers, and critically meaningful progression. We estimate that 32% of this population with elevated amyloid will progress on the Clinical Dementia Rating Global score by 4 years, and this estimate grows to 88% at 10 years,” said lead author Michael Donohue, MD, Associate Professor of Neurology at the USC Alzheimer’s Therapeutic Research Institute.

  • Clinical Implications for Study 1: Even though a small percentage of participants were observed for 10 years, the results suggest that preclinical Alzheimer disease—defined as clinically normal individuals with elevated brain amyloid—may represent a pre-symptomatic stage of the disease. Although the work did not establish a causal role of elevated amyloid in subsequent decline, the results support other findings from genetic data pointing to the critical role of amyloid in the neurobiology of Alzheimer disease.

    “We are continuing to learn about the pre-symptomatic stage of Alzheimer disease, and we are hopeful that clinical trials in this early stage, such as A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s) and EARLY, can successfully demonstrate a slowing of cognitive decline,” said Dr. Donohue, who noted that these studies are still enrolling patients.

  • 2. A Simple Saliva Test May Identify Biomarkers to Help Diagnose Alzheimer Disease: Saliva samples from 12 healthy controls, 8 persons with mild cognitive impairment (MCI), and 9 patients with Alzheimer disease were biochemically profiled using metabolomics. Researchers accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and Alzheimer disease patients compared with controls. Using logistic regression modeling, they distinguished with statistical significance MCI and Alzheimer disease from controls and MCI from Alzheimer disease.[2]

  • Clinical Implications for Study 2: This pilot study demonstrates the potential for using metabolomics and saliva for the early diagnosis of Alzheimer disease. Since collection of saliva is easy and convenient, the development of accurate, sensitive salivary biomarkers would be ideal for screening those at greatest risk for Alzheimer disease, the authors state.

  • 3. Microvascular Damage Appears to Be Tied to Depression Among Older Adults: A meta-analysis and systematic review of 48 studies, including 8 studies describing longitudinal data, provided information from 43,600 participants, 9203 individuals with depression, and 72,441 person-years. Microvascular dysfunction was found to increase the risk of depression by up to 58%, depending on how it was measured. The risk of depression was increased by 30% when MRI revealed cerebral microinfarctions.[3]

  • Clinical Implications for Study 3: Microvascular dysfunction might provide a potential target for the prevention and treatment of depression, state the authors. The results suggest that clinicians should rigorously treat cardiovascular aging to promote healthy brain aging and to prevent future mental health problems.


    1. Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317:2305-2316. doi:10.1001/jama.2017.6669

    2. Yilmaz A, Geddes T, Han B, et al. Diagnostic biomarkers of Alzheimer’s disease as identified in saliva using 1H NMR-based metabolomics. J Alzheimers Dis. 2017;58:355-359.

    3. Van Agtmaal MJM, Houben AJHM, Pouwer F, et al. Association of microvascular dysfunction with late-life depression: a systematic review and meta-analysis. JAMA Psychiatry. Published online May 31, 2017. doi:10.1001/jamapsychiatry.2017.0984

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