Biggest risk factors identified to try and prevent Alzheimer's disease

Clinicians should identify and target 10 risk factors in their attempt to prevent Alzheimer's disease, say researchers

July 20, 2020

Science Daily/BMJ

There are at least 10 risk factors that appear to have a significant impact on a person's likelihood of developing Alzheimer's disease that could be targeted with preventative steps, suggests research published in the Journal of Neurology, Neurosurgery & Psychiatry.

Focusing on these factors, which include cognitive activity, high body mass index in late life, depression, diabetes, and high blood pressure, could provide clinicians with an evidence based guideline for prevention of Alzheimer's disease, but a lot more research is needed to come up with other promising approaches to preventing the condition.

Currently, around 850,000 people in the UK are affected by dementia -- around two thirds of which are Alzheimer's disease -- and the condition is a leading cause of death, not helped by the fact that there have been no new drug treatments for dementia in almost 20 years.

Experts are predicting rising case numbers as the population ages but recent research has suggested that the number of cases appears to be reducing, possibly due to lifestyle changes, better education and risk reduction strategies to prevent or delay dementia.

Existing evidence on preventing Alzheimer's disease is challenging to interpret due to varying study designs with different endpoints and credibility.

So an international team of researchers led by Professor Jin-Tai Yu at Fudan University in China, set out to review and analyse current evidence in order to produce evidence-based suggestions on Alzheimer's disease prevention.

The researchers gathered 395 studies (243 observational prospective studies and 152 randomised controlled trials) that were suitable for their analysis.

From analysing these, they proposed 21 suggestions based on the consolidated evidence available that could be used in practice by clinicians to try to prevent Alzheimer's disease.

Within these, there were what they referred to as "Class I" suggestions to target 19 different factors.

Nearly two-thirds of these suggestions would involve targeting vascular risk factors (such as high blood pressure and cholesterol levels) and lifestyle, strengthening the importance of keeping healthy to prevent Alzheimer's disease.

Ten of the suggestions were backed by strong evidence and included receiving as much education as possible in early life, participating in mentally stimulating activities such as reading, avoiding diabetes, stress, depression, head trauma, and high blood pressure in midlife.

A further nine suggestions had slightly weaker evidence to support them and included regular physical exercise, getting sufficient good quality sleep, maintaining a healthy body weight and good heart health in later life, avoiding smoking, and including vitamin C in the diet.

In contrast, two interventions were not recommended -- oestrogen replacement therapy and use of acetylcholinesterase inhibitors (drugs that increase communication between nerve cells).

The authors point to some study limitations, such as the fact that observational studies cannot indicate a clear causal relationship and randomised controlled trials cannot be generalisable beyond the specific sample, intervention, dose and duration studied.

In addition, the values of their suggestions might be limited by geographic variability, definition of exposure and prevalence of risk factors at population level.

Nevertheless, the authors say this was the most comprehensive and large-scale systematic review and meta-analysis for Alzheimer's disease to date, and the evidence based suggestions were put together by integrating a large amount of evidence from different types of existing research.

They conclude: "This study provides an advanced and contemporary survey of the evidence, suggesting that more high-quality observational prospective studies and randomised controlled trials are urgently needed to strengthen the evidence base for uncovering more promising approaches to preventing Alzheimer's disease."

https://www.sciencedaily.com/releases/2020/07/200720190920.htm

Depression symptoms in Alzheimer's could be signs for cognitive decline

August 9, 2019

Science Daily/Massachusetts General Hospital

Depression symptoms in cognitively healthy older individuals together with brain amyloid, a biological marker of Alzheimer's could trigger changes in memory and thinking over time.

Increasingly, Alzheimer's disease (AD) research has focused on the preclinical stage, when people have biological evidence of AD but no or minimal symptoms, and when interventions might have the potential to prevent future decline of older adults. Researchers from Massachusetts General Hospital (MGH) have shed important new light on this area, reporting in a study published in JAMA Network Open that depression symptoms in cognitively healthy older individuals together with brain amyloid, a biological marker of AD, could trigger changes in memory and thinking over time.

"Our research found that even modest levels of brain amyloid deposition can impact the relationship between depression symptoms and cognitive abilities," says Jennifer Gatchel, MD, PhD, of the MGH Division of Geriatric Psychiatry, and lead author of the study. "This raises the possibility that depression symptoms could be targets in clinical trials aimed at delaying the progression of Alzheimer's disease. Further research is needed in this area"

Past research has shown an association between depression and cognitive deficits in older individuals. The MGH study, however, is among the first to reveal that this association is influenced by the presence of cortical amyloid in unimpaired older adults, even when depression symptoms are mild to moderate. Data were collected by researchers over a seven-year period from 276 community-dwelling older adults, all participants in the landmark Harvard Aging Brain Study (HABS). What they discovered was a significant link between worsening depression symptoms and declining cognition over two to seven years that was influenced by AD pathology, as measured by PET imaging of brain amyloid.

"Our findings offer evidence that in healthy older adults, depression symptoms together with brain amyloid may be associated with early changes in memory and in thinking," explains Gatchel. "Depression symptoms themselves may be among the early changes in the preclinical stages of dementia syndromes. Just as importantly, these stages represent a clinical window of opportunity for closely monitoring at-risk individuals, and for potentially introducing interventions to prevent or slow cognitive decline."

MGH researchers also learned from their extensive work that not all older adults with depression symptoms and cortical amyloid will experience failing cognition. Other risk factors investigated by the authors that could modify the relationship between depression and cognition include brain metabolism and volume of the hippocampus, the part of the brain associated with learning and forming of new memories. The authors also note that other mechanisms, including tau-mediated neurodegeneration, hypertension, hypercortisolemia and inflammation, may be involved and need to be investigated.

"These findings underscore the fact that depression symptoms are multi-factorial and may actually work synergistically with amyloid and related processes to affect cognition over time in older adults," notes Gatchel. "This is an area we will continue to actively study."

https://www.sciencedaily.com/releases/2019/08/190809113023.htm