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New Study Links Early Alzheimer's with Psychiatric Symptoms

A new study, conducted at the University of Sao Paulo (in collaboration with the Brazilian Biobank for Aging Studies) has discovered a link between the pathology of early Alzheimer’s disease (AD) in the brain, and psychiatric symptoms.  Depression, anxiety, sleep disturbances and other psychiatric symptoms may be linked with symptoms of Alzheimer’s that begin in the brain, early in the disease process.

The study was published in an October 2018 issue of the Journal of Alzheimer’s Disease.  Researchers are hopeful that evidence gathered in the study could lead to the ability to diagnose AD earlier, proving to be an instrumental new biomarker.  A biomarker is a measurable indicator of the severity or presence of a disease, such as Alzheimer’s disease. 

In addition, the study findings may suggest to medical experts a new perspective on the origins of mental illness in many seniors.

Ground Breaking New Study

The groundbreaking research may help scientists in their quest to discover a better understanding of the origins of the first stages of Alzheimer’s disease.  The new study findings will help lead medical experts to being a step closer to a finding an effective treatment to slow down the progression of AD—or possibly even prevent the development of dementia (late stage Alzheimer’s disease).

Depression and Alzheimer’s Disease

Previous studies have pointed to the possibility that depression may predispose a person to AD; but, the recent study discovered that mental health symptoms (such as depression and insomnia) are closely linked with early stage AD pathology (disease) in the brain.

Lea Grinberg, MD, PhD, at the UCSF Weill Institute for Neurosciences’ Memory and Aging Center, partnered with the Brazilian team of researchers to discover that depression and other psychiatric symptoms do NOT cause AD, but, rather, may be the earliest warning signs of the disease. 

Grinberg explained, “The discovery that the biological basis for these symptoms is the early Alzheimer’s pathology itself was quite surprising.  It suggests these people with neuropsychiatric symptoms are not at risk of developing Alzheimer’s disease—they already have it.”

Most postmortem (after death) brain studies of Alzheimer’s disease usually involves a relatively small number of samplings from older adults who showed symptoms of dementia, before they passed away.  Grinberg’s team was able to draw from a much larger population of brains of younger adults—and fewer brains of those with more than one disease.  In fact, Alex Ehrenberg, a research associate in the Grinberg lab, worked with the team from the University of Sao Paulo in studying the brains of 1092 healthy adults.

Study Findings

Alzheimer’s symptoms in the brain are characterized by the build-up of proteins, called amyloid plaques and neurofibrillary tangles (also called tau tangles).  Healthy tissue in the brain begins to shrink in the areas where tau and amyloid accumulate.

Alzheimer’s disease usually progresses with tau tangles appearing initially in the brainstem area—which is associated with processing emotions, appetite and sleep.  The amyloid plaques normally show up in the cortical regions of the brain,then spread to deeper areas. The cortical areas are thought to be higher processing areas of the brain.

Ehrenberg and his team categorized each of the post mortem brains according to the progression of AD, based on the level of amyloid and tau accumulation.  Next, the team evaluated the donors’ emotional and cognitive status—from questioning family members and caregivers who were with the donor on a regular basis, in the last 6 months of life. 

The analysis indicated that in those whose brains had the early stages of tau tangles, but lacked memory changes, there was a reported increase of one or more psychiatric symptom, including anxiety, changes in appetite, depression, sleep disturbances, or agitation.

As the tau accumulation increased in the brainstem and started to spread out to other regions of the brain, so too did the symptoms of agitation, but, only in the later stages of tau buildup—when the pathology began to reach the brain’s outer cortex—did the person start exhibiting symptoms of dementia (such as memory decline and cognitive deficits).

Ehrenberg explained, “These results could have major implications for Alzheimer’s drug trials focused on early degenerative changes, where people have been seeking tractable clinical outcomes to target in addition to early cognitive decline.”  Ehrenberg added that the study findings will become even more useful as new diagnostic technologies become available for finding signs of early stage AD pathology, such as PET imaging of tau and blood biopsies. 


The Journal of Alzheimer’s Disease reports that this new discovery linking psychiatric symptoms with early Alzheimer’s is said by Grinberg to be “as exciting as the implications for Alzheimer’s disease itself.”

Learn more about new Alzhimer’s clinical research studies on products for Alzheimer’s treatment, by visiting the Alzheimer’s Drug Discovery Foundation/Cogntive Vitality.

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