Metacognitive Performance on Memory and Visuospatial Tasks in Functional Cognitive Disorder.

Functional Cognitive Disorder (FCD) is a common diagnosis at the memory clinic. FCD is characterised by significant self-reported cognitive symptoms in the absence of external evidence of cognitive dysfunction. A potential explanation for this is a deficit in metacognition, the process by which we internally judge our own abilities. Here we investigated differences in accuracy, confidence, and metacognition between people with FCD (N = 20), neurodegenerative mild cognitive impairment (nMCI; N = 14), and healthy controls (N = 23). The groups were assessed on forced choice memory and perceptual tasks, with trial by trial confidence ratings. FCD and nMCI participants showed lower accuracy on the memory task (means FCD 63.65%, nMCI 63.96%, HC 71.22%), with a significant difference between the FCD and HC groups after controlling for age and sex. There were no between-group differences in memory task confidence (means FCD 3.19, nMCI 3.59, HC 3.71). The FCD group showed greater confidence when longer time was allowed on the memory task. No between group differences in perceptual task accuracy (means FCD 63.97%, nMCI 64.50%, FCD 65.86%) or confidence (means FCD 3.71, nMCI 3.43, HC 3.88) were found. No differences in metacognitive efficacy emerged between the groups, either on the memory or perceptual task (Memory Meta-d'/d':FCD 0.63, nMCI 0.94 HC 0.85; Perceptual Meta-d',d': FCD 0.50, nMCI 0.51, HC 0.72). Participants showed greater metacognitive efficacy on the memory task compared to the perceptual task. The difficulties experienced by people with FCD do not appear to be due to metacognitive deficits. Their performance was similar to people with nMCI over aspects of the memory tasks, which suggests that the primary issue may lie with memory encoding or retrieval, rather than with their judgement of performance accuracy.

Differentiating Functional Cognitive Disorder from Early Neurodegeneration: A Clinic-Based Study.

Functional cognitive disorder (FCD) is a relatively common cause of cognitive symptoms, characterised by inconsistency between symptoms and observed or self-reported cognitive functioning. We aimed to improve the clinical characterisation of FCD, in particular its differentiation from early neurodegeneration. Two patient cohorts were recruited from a UK-based tertiary cognitive clinic, diagnosed following clinical assessment, investigation and expert multidisciplinary team review: FCD, (n = 21), and neurodegenerative Mild Cognitive Impairment (nMCI, n = 17). We separately recruited a healthy control group (n = 25). All participants completed an assessment battery including: Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test Part B (TMT-B); Depression Anxiety and Stress Scale (DASS) and Minnesota Multiphasic Personality Inventory (MMPI-2RF). In comparison to healthy controls, the FCD and nMCI groups were equally impaired on trail making, immediate recall, and recognition tasks; had equally elevated mood symptoms; showed similar aberration on a range of personality measures; and had similar difficulties on inbuilt performance validity tests. However, participants with FCD performed significantly better than nMCI on HVLT-R delayed free recall and retention (regression coefficient -10.34, p = 0.01). Mood, personality and certain cognitive abilities were similarly altered across nMCI and FCD groups. However, those with FCD displayed spared delayed recall and retention, in comparison to impaired immediate recall and recognition. This pattern, which is distinct from that seen in prodromal neurodegeneration, is a marker of internal inconsistency. Differentiating FCD from nMCI is challenging, and the identification of positive neuropsychometric features of FCD is an important contribution to this emerging area of cognitive neurology.

Accelerated long-term forgetting in healthy older adults predicts cognitive decline over 1 year.

BACKGROUND: Here, we address a pivotal factor in Alzheimer's prevention-identifying those at risk early, when dementia can still be avoided. Recent research highlights an accelerated forgetting phenotype as a risk factor for Alzheimer's disease. We hypothesized that delayed recall over 4 weeks would predict cognitive decline over 1 year better than 30-min delayed recall, the current gold standard for detecting episodic memory problems which could be an early clinical manifestation of incipient Alzheimer's disease. We also expected hippocampal subfield volumes to improve predictive accuracy. METHODS: Forty-six cognitively healthy older people (mean age 70.7 ± 7.97, 21/46 female), recruited from databases such as Join Dementia Research, or a local database of volunteers, performed 3 memory tasks on which delayed recall was tested after 30 min and 4 weeks, as well as Addenbrooke's Cognitive Examination III (ACE-III) and CANTAB Paired Associates Learning. Medial temporal lobe subregion volumes were automatically measured using high-resolution 3T MRI. The ACE-III was repeated after 12 months to assess the change in cognitive ability. We used univariate linear regressions and ROC curves to assess the ability of tests of delayed recall to predict cognitive decline on ACE-III over the 12 months. RESULTS: Fifteen of the 46 participants declined over the year (≥ 3 points lost on ACE-III). Four-week verbal memory predicted cognitive decline in healthy older people better than clinical gold standard memory tests and hippocampal MRI. The best single-test predictor of cognitive decline was the 4-week delayed recall on the world list (R2 = .123, p = .018, ß = .418). Combined with hippocampal subfield volumetry, 4-week verbal recall identifies those at risk of cognitive decline with 93% sensitivity and 86% specificity (AUC = .918, p < .0001). CONCLUSIONS: We show that a test of accelerated long-term forgetting over 4 weeks can predict cognitive decline in healthy older people where traditional tests of delayed recall cannot. Accelerated long-term forgetting is a sensitive, easy-to-test predictor of cognitive decline in healthy older people. Used alone or with hippocampal MRI, accelerated forgetting probes functionally relevant Alzheimer's-related change. Accelerated forgetting will identify early-stage impairment, helping to target more invasive and expensive molecular biomarker testing.

The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory.

Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss.

Measuring Information Processing Speed in Mild Cognitive Impairment: Clinical Versus Research Dichotomy.

A substantial body of research evidence is indicative of disproportionately slowed information processing speed in a wide range of multi-trial, computer-based, neuroimaging- and electroencephalography-based reaction time (RT) tests in Alzheimer's disease and mild cognitive impairment (MCI). However, in what is arguably a dichotomy between research evidence and clinical practice, RT associated with different brain functions is rarely assessed as part of their diagnosis. Indeed, often only the time taken to perform a single, specific task, commonly the Trail making test (TMT), is measured. In clinical practice therefore, there can be a failure to assess adequately the integrity of the rapid, serial information processing and response, necessary for efficient, appropriate, and safe interaction with the environment. We examined whether a typical research-based RT task could at least match the TMT in differentiating amnestic MCI (aMCI) from cognitively healthy aging at group level. As aMCI is a heterogeneous group, typically containing only a proportion of individuals for whom aMCI represents the early stages of dementia, we examined the ability of each test to provide intra-group performance variation. The results indicate that as well as significant slowing in performance of the operations involved in TMT part B (but not part A), individuals with aMCI also experience significant slowing in RT compared to controls. The results also suggest that research-typical RT tests may be superior to the TMT in differentiating between cognitively healthy aging and aMCI at group level and in revealing the performance variability one would expect from an etiologically heterogeneous disorder such as aMCI.

Subjective Memory Complaints: Symptoms and Outcome in Different Research Settings.

Subjective memory complaints (SMC) are important and may, in certain individuals, herald the onset of neurodegenerative diseases such Alzheimer's disease. However, they are very common and in some individuals will result from mood disorders/personality factors or systemic illnesses. Research has been hampered by the wide variety of criteria and neuropsychological tests used to define this disorder. Different terminology has also hindered the ability to generate generalizable results. We evaluate how subjects with SMC are defined within different research settings (community, primary care, and memory clinic), their rates of progression to mild cognitive impairment and dementia, and how individuals within these contexts differ in terms of complaints, personal characteristics, and help-seeking behavior.

Functional Cognitive Disorder: A Common Cause of Subjective Cognitive Symptoms.

Patients frequently present to the memory clinic with self-reported cognitive symptoms that cannot be attributed to structural, toxic, or metabolic causes, and are out of keeping with their performance on neuropsychological assessment. This can be considered to be Functional (psychosomatic) Cognitive Disorder, which results in significant patient distress and often has a major impact on social functioning and employment. We performed a retrospective analysis of the Bristol ReMemBr group cognitive clinic database to ascertain the prevalence of Functional Cognitive Disorder, review the patient characteristics, and develop new guidelines for diagnosis and management. 196 patients were screened of whom 23 were diagnosed with Functional Cognitive Disorder; the oldest patient with this diagnosis was aged 60 years at symptom onset. When considering only those presenting below the age of 60 years (total no. held on database = 69), a third were diagnosed with Functional Cognitive Disorder. On neuropsychological testing, 47% had an atypical (invalid) pattern of results, or failed tests of performance validity. Of those with valid neuropsychological results, 80% scored in the normal range. Depression and anxiety were common but did not appear to be the primary cause of cognitive symptoms. Particular characteristics seen were excessively low self-rating of memory ability, and discrepancies between perceived and actual cognitive performance. The rate of unemployment was high, often due to the cognitive symptomatology. This is an important disorder to address, being common in working adults, and carrying a risk of misdiagnosis as early neurodegeneration, with subsequent inappropriate treatment and inclusion in clinical trials.

Functional cognitive disorder: what is it and what to do about it?

To err is human, and it is normal to make minor cognitive errors from time to time. Some people experience persistent subjective cognitive difficulties that cause distress and functional impairment, with no underlying structural, neurodegenerative, toxic or metabolic cause. This is considered a form of functional disorder. In this article, we review functional cognitive disorder and outline its core clinical features. Patients with this are typically of working age and have a source of psychological distress, such as chronic pain, work stress or family difficulties. Its distinction from incipient dementia is difficult and usually requires interval follow-up. Pointers towards possible dementia include abnormal neuroimaging or loss of insight. Many patients accept a functional cognitive disorder diagnosis and willingly engage with psychological therapies but there is no defined optimal treatment. Functional cognitive disorder is common but under-studied; future research priorities include the development of clear diagnostic criteria and robust trials of therapeutic strategies.

Do memory-impaired individuals report stable attitudes?

This research explored whether individuals diagnosed with probable Alzheimer's disease report stable attitudes. Two groups of participants (16 memory-impaired individuals with dementia and 16 matched controls without memory impairment) were presented with photos of various common objects and asked to indicate their attitude towards each object. Participants completed this task on two occasions, separated by 1 week. The results of the experiment revealed that memory-impaired individuals showed significant stability across time in their attitudes, although their level of attitude stability was less pronounced than that demonstrated by the matched controls. Theoretical and applied implications of the results are discussed.