Critical Review
Late-Life Anxiety and Cognitive Impairment: A Review

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Emerging research implicates a consistent reciprocal relationship between late-life anxiety and cognition. Understanding this relationship may clarify pathophysiological substrates of cognitive impairment and why co-occurring anxiety and cognitive impairment relates to poorer treatment prognosis for both conditions. This article critically reviews evidence of more prevalent anxiety in cognitively impaired older adults, elevated anxiety related to poorer cognitive performance, and more severe anxiety symptoms predicting future cognitive decline. It considers pathophysiologic mediators and moderators, and the influence of comorbid depression or medical illness in anxiety. Identified directions for future research includes use of in-depth anxiety assessment comparing normal and mild cognitively impaired older adults and use of challenging neuropsychological tests to determine if specific cognitive domains suffer in anxious older adults.

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PREVALENCE AND CHARACTERISTICS OF LATE-LIFE ANXIETY

GAD, characterized by pervasive, excessive, and uncontrollable apprehension or worry about everyday situations, is the most common DSM–IV–TR5 anxiety disorder in older individuals with a lifetime prevalence of 10.2%.12 The DSM–IV diagnostic criteria for GAD requires that worry symptoms occur for 6 months or longer, the worry is difficult to control, and that three or more anxiety-related somatic symptoms are present: irritability, concentration problems, restlessness, sleep difficulty, muscle

ANXIETY SYMPTOMS AS CORRELATES AND PREDICTORS OF COGNITIVE IMPAIRMENT IN OLDER ADULTS

Cross-sectional investigations generally support the hypothesis that the presence or severity of anxiety is associated with lower cognitive performance in older adults, with effect sizes generally in the moderate range. Studies assessing measures of learning and memory (i.e., episodic memory tasks) typically yield larger effects than are observed for other cognitive domains (Table 1). Among older adults with subjective memory complaints, those reporting high anxiety or depressive symptoms

THE ONSET AND DEVELOPMENT OF ANXIETY IN COGNITIVELY IMPAIRED OLDER ADULTS

Late-life cognitive problems are best conceptualized on a spectrum from normal age-related decline to MCI, and at the extreme, dementia.22 As many as 30% of older adults in the general population meet diagnostic guidelines for MCI,23 considered a heterogeneous category varying by the presence or absence of memory impairment, and cognitive impairment in one or multiple domains.22 Amnestic MCI, in particular, is hypothesized as a prodrome of neurodegenerative dementia.22 Comorbid anxiety symptoms

PATHOPHYSIOLOGICAL MECHANISMS

Structural changes in the brain offer a common potential substrate between late-life anxiety and cognition. Although there are numerous neuroimaging investigations of such anxiety disorders as posttraumatic stress disorder, phobias and obsessive compulsive disorder, very few have directly examined GAD. One of the few such studies of patients implicates functional impairments in the dorsolateral region of the prefrontal cortex,40 an area strongly influencing diverse cognitive processes,

COMORBID DEPRESSIVE SYMPTOMS

Another important consideration is the contribution of comorbid depressive symptoms. Lifetime prevalence of developing a mood disorder in the context of GAD is as high as 8060 and the incidence of GAD in Alzheimer patients with a mood disorder is 26%.61 Multiple shared vulnerabilities between GAD and major depressive disorder, including similar genetic risks60, 62 and personality correlates63 have led to the proposal that the two disorders belong in the same diagnostic category,62 whereas

COMORBID MEDICAL CONDITIONS IN ANXIETY: POTENTIAL INTERACTIONS WITH COGNITION

As noted by Cohen,65 “the diversity of anxiety disorders is remarkable, as is the wide range of conditions with which anxiety is associated” (p. 1). Common comorbidities of anxiety include other psychiatric symptoms or disorders and medical illness. Stress related to chronic medical illness may be the source of anxiety for some older adults. For others, anxiety symptoms (e.g., heart palpitations) may be misinterpreted as health-related problems. Mutual interaction and exacerbation between

TREATMENT CONSIDERATIONS

Pharmacological agents are frequently used to treat dementia and hold promise as an intervention to slow the rate of memory impairment in MCI. Combined pharmacological treatment for memory impairment and emotional problems is not uncommon in clinical settings. Due to the increased risk of nursing home placement when an older adult has anxiety symptoms comorbid to dementia,72 improving management of anxiety and other neuropsychiatric symptoms is imperative. Additional treatment options for

SUMMARY

To review, the importance of the interrelationship between anxiety and cognition depends on the clinical significance of these symptoms. Normal aging decrements in memory or transient, low levels of state anxiety generally do not seem to have a negative impact on older adult, whereas clinically relevant anxiety symptoms and cognitive decrements do. Overlapping pathophysiological mechanisms in the brain (i.e., structures, neurochemicals, endocrine functions) offer a potential substrate for this

RECOMMENDATIONS AND FUTURE DIRECTIONS

As illustrated throughout this article, issues associated with anxiety in the context of late-life cognitive impairment are complex, but have the potential to illuminate our understanding of preclinical dementia and optimal treatment approaches for late-life GAD. More research is needed to track the longitudinal course of anxiety and cognition. Moreover, longitudinal observational studies examining the order in which anxiety symptoms or cognitive impairment first appear may be essential for

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  • Cited by (0)

    The authors thank Brian Yochim, Ph.D. for his helpful comments on this paper, and Tiffany Rideaux, B.A. for her advice and input on this work.

    Writing of this manuscript was partly supported by the Office of Academic Affiliations; VA Special MIRECC Fellowship Program in Advanced Psychiatry and Psychology; National Institutes of Health Grants AG18784, AG17824, and MH70886; and the Department of Veterans' Affairs, Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC).

    Received September 31, 2007

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