Anxiety Tied to Dementia

Nancy A. Melville

July 27, 2016

Anxiety may be associated with an increased risk for cognitive decline and dementia, with the strongest associations in older patients, a new meta-analysis focusing on community populations shows.

"Irrespective of the association is causal or not, it is important for the clinician to be aware of anxiety as a possible predictor for dementia, especially when the anxiety emerges at late life," the investigators, with first author Bernice Gulpers, Department of Psychiatry and Psychology, the School for Mental Health and Neuroscience, Maastricht University Medical Center, and Alzheimer Center Limburg, the Netherlands, write.

Mild cognitive impairment (MCI) is a known risk factor for dementia, and although depression and anxiety have been shown to be the most common psychiatric disorders that copresent with MCI, most research has focused on depression, the authors note.

To better understand the role of anxiety, the researchers conducted a literature search of longitudinal studies published through January 2015 that focused on anxiety as a possible risk factor for cognitive decline.

The findings were published online July 4 in the American Journal of Geriatric Psychiatry.

Among 20 studies that met inclusion criteria, anxiety was found to predict incident cognitive impairment in the community in four studies, which included 4155 patients (risk ratio [RR], 1.77; P < .001). Incident dementia was found to predict cognitive impairment in six studies, which included 6004 patients (RR = 1.57; P = .04).

The association between anxiety and dementia was stronger among individuals aged 80 years and older (RR, 2.51; P < .01) in comparison with people younger than 80 years (RR, 1.23; P < .33).

Among cases of clinical MCI in patients recruited at memory clinics, the link between anxiety and the conversion to dementia was not statistically significant (RR = 1.21; P = .20), which may the result of referral bias, the authors note.

"This finding highlights that people should be cautious with interpreting results from clinical samples, as they often cannot be generalized to the general population," the researchers note.

In terms of a relationship between anxiety and a decline in individual cognitive domains, studies were too heterogeneous to be pooled. No association was seen in domains of speed of information processing, attention, language, verbal fluency, and visuospatial functioning.

"We only found some suggestions that anxiety predicts rate of decline on executive functioning, but this is inconclusive," the investigators write.

Hypotheses regarding mechanisms behind anxiety as a possible causative factor influencing cognitive decline and dementia include hypercortisolism, cardiovascular disease, low-grade inflammation, brain-derived neurotrophic factor suppression, and the cognitive reserves.

"There are studies which found evidence for all these different hypotheses," Gulpers told Medscape Medical News.

For example, it has been suggested that cortisol-induced overstimulation of glucocorticoid receptors in the medial temporal lobe may lead to hippocampus atrophy and that the physiologic reactions to anxiety, including increased heart rate and blood pressure, which are associated with cardiovascular disease, could lead to subsequent vascular dementia.

"Dementia, however, is a broad diagnosis which involves different etiologies ― for example, Alzheimer's disease and vascular dementia," Gulpers said. "I personally do not think that only one hypothesis is going to fully explain the association between anxiety and the dementia syndrome, if it even is causally related."

A better understanding of the role of anxiety, however, could have important clinical implications, she added.

"Treatment of anxiety complaints is very important, independent of whether it is causally related or not," Gulpers said.

"[If] anxiety is a causal factor leading to cognitive decline and dementia, the regular treatment of cognitive-behavioral therapy could potentially slow the progression. But when anxiety is a prodromal symptom of dementia, a better approach would be the structuring of daily life," she added.

Am J Geriatr Psychiatry. Published online July 4, 2016. Abstract

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