ReviewFunctional cognitive disorders: a systematic review
Introduction
Increasing numbers of people seek help for memory problems, and yet many symptomatic patients attending memory clinics do not have degenerative brain disease, and do not progress to dementia.1, 2 Cognitive symptoms or impairment might be caused by other medical and neurological disorders, or by prescribed or non-prescribed drugs, but the experience of cognitive failure can also arise through purely functional disturbances to cognitive and introspective processes.
Functional cognitive disorders are a group of over-lapping conditions in which cognitive symptoms are present, which are genuine, distressing, and often disabling, but experienced inconsistently and not related to systemic or brain disease (panel).3 They can be included under the umbrella of functional neurological disorders, one of the most common causes of neurological disability.5, 6 Although historically defined in terms of psychological stress and absence of disease, functional neurological disorders are now also understood in neurobiological terms, with evidence of dysregulated attention, sensorimotor prediction, self-agency, and emotional processing.7, 8 Psychological stressors are no longer required for the diagnosis of functional neurological disorder, which, crucially, is only made on the basis of positive clinical features showing characteristic internal inconsistency; misdiagnosis is rare.9
Functional cognitive symptoms have received less research attention than other functional symptoms, although the interest in the field is developing. Teodoro and colleagues4 systematically reviewed the literature on so-called brain fog, and cognitive symptoms in functional neurological disorders, fibromyalgia, and chronic fatigue syndrome, suggesting a unifying theory in which excessive attention towards physical symptoms and cognitive processes generates symptoms. Bailey and colleagues10 systematically reviewed patterns of communication in memory clinics, identifying features with potential to discriminate between functional and neuro-degenerative disorders: individuals with functional disorders were more likely to attend alone, to be worried about their memory, and to provide a detailed account of personal history and memory failures than patients with neurodegenerative disease.
However, despite increasing interest in identifying early prodromes of degenerative brain diseases, no detailed examination has been done of the prevalence and clinical associations of functional cognitive disorders (an important differential diagnosis) in the cognitive disorder literature. One reason for this scarcity of such research might be that the scientific literature concerning functional cognitive disorders is a tangled landscape of overlapping terminology.
Physicians from the early 20th century used the term pseudodementia to describe a wide range of clinical syndromes with the appearance of dementia but rather caused by depression, conversion disorders (also sometimes called hysteria), dissociative states (including so-called Ganser states), or disordered personality.11, 12, 13 The broader pseudodementia concept has been superseded by depressive pseudodementia (ie, cognitive impairment associated with severe depression), although with better recognition of the frequency of depression and anxiety in prodromal degenerative brain disease, this clinical group is seen to be aetiologically heterogenous.
During the past 10 years, researchers investigating subjective cognitive decline have been strongly invested in identifying early clinical markers of neurodegenerative disease, rarely focusing on alternative causes of symptoms. People with subjective cognitive complaints but normal cognitive examination are sometimes described, unhelpfully, as worried well (ie, describing worry about experiences that fall within the range of normal, and that are not because of disease). Of equal concern, people with both subjective cognitive complaints and impairment on testing (therefore defined as having mild cognitive impairment), or with subjective cognitive complaints and biomarkers suggestive of an underlying disease process, might receive life-changing predictions or diagnoses of dementia that are retained even when inconsistent symptom experience and subsequent cognitive trajectory are more consistent with a functional disorder than dementia.14
An almost universal tendency exists in dementia research to view subjective cognitive symptoms as a preliminary to mild cognitive impairment and later dementia. However, an as yet undefined proportion of those individuals with symptoms described in terms of subjective cognitive decline, subjective memory impairment, pseudodementia, or as the worried well, might be better described in positive terms as having the inclusively generated diagnosis of functional cognitive disorders—challenging the prevailing model that subjective cognitive decline always leads to mild cognitive impairment, which in turn always leads to dementia. We aimed to systematically search and review the literature incorporating these diverse terms to assess their usage, and the prevalence and clinical associations of functional cognitive disorders in people with cognitive symptoms.
Section snippets
Search strategy and selection criteria
We did two simultaneous searches (A and B) of the published peer-reviewed English language literature in MEDLINE, Embase, and PsycINFO databases from inception to March 14, 2019. We included observational studies describing the cross-sectional diagnoses of those assessed for possible dementia in memory clinics or similar services, and observational studies (excluding treatment studies) that included (albeit not necessarily as a primary focus) original data on at least ten adults (>18 years)
Results
Of the 249 included studies (figure 1, appendix pp 19–29), 185 studies had a cross-sectional design, 59 studies had a longitudinal design, and five studies described case series with at least ten people; 59 studies included at least one control group. A wide range of terms was used to describe non-dementia cognitive symptom profiles and diagnoses (appendix p 1).
Discussion
Cognitive symptoms are common: according to this Review they are present in around a third of the population, with no clear relation to age. This finding alone confirms that not all cognitive symptoms are caused by degenerative brain disease. In studies of people presenting to memory clinics, we found that only 53% (6285 of 11 807) received dementia diagnoses, and in studies including adequate description of diagnoses, 24% (2832 of 12 003) were described as having subjective cognitive
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