Anxiety: An early indicator of Alzheimer’s disease?

A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of Alzheimer's disease in older adults.

Alzheimer's disease is a neurodegenerative condition that causes the decline of cognitive function and the inability to carry out daily life activities. Past studies have suggested depression and other neuropsychiatric symptoms may be predictors of AD's progression during its "preclinical" phase, during which time brain deposits of fibrillar amyloid and pathological tau accumulate in a patient's brain. This phase can occur more than a decade before a patient's onset of mild cognitive impairment. Investigators at Brigham and Women's Hospital examined the association of brain amyloid beta and longitudinal measures of depression and depressive symptoms in cognitively normal, older adults. Their findings, published today by The American Journal of Psychiatry, suggest that higher levels of amyloid beta may be associated with increasing symptoms of anxiety in these individuals. These results support the theory that neuropsychiatric symptoms could be an early indicator of AD.

"Rather than just looking at depression as a total score, we looked at specific symptoms such as anxiety. When compared to other symptoms of depression such as sadness or loss of interest, anxiety symptoms increased over time in those with higher amyloid beta levels in the brain," said first author Nancy Donovan, MD, a geriatric psychiatrist at Brigham and Women's Hospital. "This suggests that anxiety symptoms could be a manifestation of Alzheimer's disease prior to the onset of cognitive impairment. If further research substantiates anxiety as an early indicator, it would be important for not only identifying people early on with the disease, but also, treating it and potentially slowing or preventing the disease process early on." As anxiety is common in older people, rising anxiety symptoms may prove to be most useful as a risk marker in older adults with other genetic, biological or clinical indicators of high AD risk.

Researchers derived data from the Harvard Aging Brain Study, an observational study of older adult volunteers aimed at defining neurobiological and clinical changes in early Alzheimer's disease. The participants included 270 community dwelling, cognitively normal men and women, between 62 and 90 years old, with no active psychiatric disorders. Individuals also underwent baseline imaging scans commonly used in studies of Alzheimer's disease, and annual assessments with the 30-item Geriatric Depression Scale (GDS), an assessment used to detect depression in older adults.

The team calculated total GDS scores as well as scores for three clusters symptoms of depression: apathy-anhedonia, dysphoria, and anxiety. These scores were looked at over a span of five years.

From their research, the team found that higher brain amyloid beta burden was associated with increasing anxiety symptoms over time in cognitively normal older adults. The results suggest that worsening anxious-depressive symptoms may be an early predictor of elevated amyloid beta levels – and, in turn AD — and provide support for the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.

Donovan notes further longitudinal follow-up is needed to determine whether these escalating depressive symptoms give rise to clinical depression and dementia stages of Alzheimer's disease over time.

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Paper cited: Donovan et al. "Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults" The American Journal of Psychiatry DOI: 10.1176/appi.ajp.2017.17040442

The study was supported by the National Institute on Aging (grants R03 AG045080, R01 AG027435, K24 AG035007), the Harvard Medical School Department of Psychiatry Dupont-Warren Fellowship and Livingston Award, the Rogers Family Foundation, the Massachusetts Alzheimer's Disease Research Center (grant P50 AG005134), and the Harvard Aging Brain Study (grants P01 AGO36694, R01 AG037497). Dr. Donovan received salary support from Eisai and Eli Lilly; her spouse is employed by Alkermes. Dr. Marshall has received salary support from Eisai and Eli Lilly and has served as a consultant for Halloran and GliaCure. Dr. Hanseeuw has received grants from the Belgian National Science Foundation (grant SPD28094292) and the Belgian Foundation for Alzheimer Research (grant P16008) and has served on an advisory board as a paid consultant for GE Healthcare. Dr. Rentz has served as a consultant for Eli Lilly, Janssen Alzheimer Immunotherapy, Biogen Idek, and Lundbeck Pharmaceuticals, and she has served on the scientific advisory board for Neurotrack. Dr. Johnson has served as a consultant for AbbVie, AZtherapies, Biogen, Bristol-Myers Squibb, GE Healthcare, Genentech, Genzyme, Isis Pharmaceuticals, Janssen Alzheimer's Immunotherapy, Lundbeck, Merck, Novartis, Piramal, Roche, and Siemens Medical Solutions; he is a site principal investigator or co-investigator for Biogen, Eisai, Eli Lilly/Avid, Janssen Alzheimer Immunotherapy, Merck, and Navidea clinical trials; and he has spoken at symposia sponsored by GE Healthcare, Janssen Alzheimer's Immunotherapy, Lundbeck, and Pfizer. Dr. Sperling has served as a consultant for AbbVie, Biogen, Bracket, GE, Genentech, Lundbeck, Merck, Otsuka, Pfizer, Roche, and Sanofi; she has served as a co-investigator for Avid, Eli Lilly, and Janssen Alzheimer Immunotherapy clinical trials; she has spoken at symposia sponsored by Biogen, Eli Lilly, and Janssen Alzheimer Immunotherapy; and her spouse has received payments from Lundbeck, Novartis, Piramal Healthcare, and Siemens. The other authors report no financial relationships with commercial interests.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits and nearly 46,000 inpatient stays, is the largest birthing center in Massachusetts and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 3,000 researchers, including physician-investigators and renowned biomedical scientists and faculty supported by nearly $666 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

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http://dx.doi.org/10.1176/appi.ajp.2017.17040442

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