April 30, 2018

expert reaction to a review of the association between mid-life anxiety and later life dementia

Researchers publishing a systematic review in BMJ Open, examine the association between mid-life anxiety and long-term risk for dementia.

Dr Anita McGrogan, Epidemiologist and Senior Lecturer in Pharmacy & Pharmacology, University of Bath, said:

“The conclusions from the systematic review are rightly cautious: their results are based on four studies and three of these studies were small (one not very precise, one not significant, one of borderline significance). The remaining study may indicate something to study in the future.

“Possibly there is something here that needs further work but from the review it looks like anxiety was found at different points in time for the different studies: this highlights that it can be tricky to determine anxiety long enough before the early symptoms of dementia appear (e.g. did the anxiety occur because of early concern about the start of dementia symptoms?).”

Dr Zuzana Walker, Reader in Elderly Psychiatry, UCL, said:

“The link between midlife anxiety and subsequent dementia is fairly robust. However, it cannot be ruled out that unmeasured third factors were responsible for both anxiety and dementia (e.g. genetics/environmental factors – either of which could predispose to anxiety and dementia). Furthermore, although the studies reviewed included 30,000 participants, the majority of these (27,000) came from a single study. Therefore care must be taken in interpreting the results. In order to establish if the link between anxiety and dementia is causative, patients with anxiety would need to be randomly assigned to treatment or not at midlife, and then these 2 groups followed up for decades. These designs are known to be extremely challenging from a practical and financial perspective.

“The link is consistent with existing research showing that depression is a strong risk factor for dementia, and depression and anxiety are frequently comorbid disorders. This study further supports the idea that it is important to treat anxiety and depression during adult life, as this not only improves people’s wellbeing, quality of life and physical health, but could also reduce the long term risk of dementia.”

Prof Rob Howard, Professor of Old Age Psychiatry, UCL:

“This is a carefully conducted and written review of the potential association between mid-life anxiety symptoms and the later development of dementia. Although the authors found that there was a positive association, the authors have been extremely clear in pointing out that they can’t exclude the likely possibility that anxiety is part of the prodromal symptoms of dementia rather than representing a causal risk factor.

“Increasingly, we are recognising that a diagnosis of Alzheimer’s disease, made when the degree of neuropathology and brain cell death is sufficient to cause dementia, may represent only a late stage in the illness. Accumulation of neuropathology over 20 or 30 years is now considered to have come first, often with accompanying mood, sleep disturbance or anxiety symptoms that may represent the earliest clinical signs of Alzheimer’s disease.”

Dr Jennifer Wild, Associate Professor, Oxford Centre for Anxiety Disorders & Trauma, University of Oxford:

“The findings are interesting but fail to take into account hormonal changes that occur in mid-life. For men, mid-life changes in testosterone can influence anxiety and memory functioning as can changes in progesterone for women.  I would want to see analyses where the relationship between anxiety and later dementia is investigated whilst controlling for initial hormone levels.  People with severe mid-life anxiety may benefit from tests to check levels of key hormones. If hormone levels are within normal ranges, and anxiety is an issue, then evidence-based treatments, such as CBT, may help to reduce anxiety, which in turn may protect individuals in the long-run.

“Anxiety is debilitating and causes people to suffer.  Anxiety at any age warrants treatment.  However, without further research, it is difficult to draw conclusions about a possible link between reducing anxiety and improving cognitive function in the older brain.”

Prof Martin Rossor, NIHR National Director for Dementia Research, University College Hospitals, & Professor of Clinical Neurology, UCL, said:

“This is a carefully conducted systematic review that adds important information to potential risk factors for dementia. The authors are also careful to point out the limitations. As with all such studies association is different from causation and so it cannot be assumed that reducing anxiety will prevent the development of dementia.

“It is possible that anxiety is a very early feature of a dementing illness. We know that Alzheimer’s disease, the commonest cause of dementia, can cause subtle changes well before memory declines although the authors were careful to restrict the study to anxiety at least ten years before a diagnosis. It is also possible that anxiety might lead to behaviours such as smoking and high alcohol use that independently increase dementia risk”

Prof Masud Husain, Professor of Neurology & Wellcome Trust Principal Fellow, University of Oxford, said:

“This appears to be a carefully conducted analysis of previous studies. The findings suggest that anxiety is associated with a significantly higher risk for a subsequent diagnosis of dementia.

“The results have to be considered with caution. They certainly don’t mean that all people with anxiety – which is a very common condition – are at higher risk. Nor is it clear how anxiety might be linked to dementia. Is it that anxiety in some way predisposes to earlier onset of dementia? Or is anxiety simply a marker of early brain changes that eventually would lead to dementia in any event? These findings don’t tell us whether more aggressive treatment of anxiety would lead to reduced risks of developing dementia, but there might be other good health reasons to do this anyway.”

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, said:

“Mental health conditions like anxiety and depression have been linked to dementia before and many overlapping symptoms make a dementia diagnosis difficult. This review took a high-quality approach, combining findings from four existing studies exploring anxiety as a risk factor for dementia. This approach revealed a link between anxiety in midlife and dementia, but large differences between the individual studies meant researchers were unable to comprehensively analyse the results.

“It’s important to remember that just because there is an association between the two factors does not necessarily mean that anxiety causes dementia. Dementia is caused by a complex mix of risk factors including age and genetics and although this study looked at dementia in people more than ten years after being diagnosed with anxiety, we know the diseases leading to dementia can begin in the brain up to twenty years before any symptoms show.

“Much more research is required to understand the mechanisms underpinning this link, and to see if different forms of anxiety treatment could have any effect on dementia risk. Anyone who is concerned about their mental health they should seek advice from their doctor.”

* ‘Support for midlife anxiety diagnosis as an independent risk factor for dementia: a systematic review’ by Gimson et al. published in BMJ Open on Monday 30 April. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/dementia/

Declared interests

Dr Anita McGrogan: No conflicts of interest.

Prof Rob Howard: No conflicts of interest.

Dr Jennifer Wild: I have no conflicts of interest to declare.

Prof Martin Rossor: “No conflicts except I am the NIHR National Director for Dementia Research.”

Prof Masud Husain: No conflicts of interest.

None others received.