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Diagnosis of Dementia and Cognitive Impairment

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A special issue of Diagnostics (ISSN 2075-4418).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 52704

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Dr. Andrew J. Larner

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Cognitive Function Clinic, Walton Centre for Neurology & Neurosurgery, Liverpool, UK

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Dear Colleagues,

Dementia and cognitive impairment represent one of the most pressing clinical and social issues of our time, issues likely to escalate as the world population ages. The need to identify individuals with dementia and cognitive impairment in order to initiate appropriate treatment and management options is self-evident, yet it remains the case that many afflicted individuals remain undiagnosed, the so-called "dementia diagnosis gap". Various methods to facilitate the accurate diagnosis of dementia and cognitive impairment may be used, including neurological examination for particular signs, the administration of cognitive screening instruments, various neuroimaging techniques, and the examination of cerebrospinal fluid for disease biomarkers. Increased societal awareness of dementia may have prompted an increased frequency of presentation of individuals with purely subjective memory complaints, making functional cognitive disorders an important differential diagnosis of cognitive impairment.

The primary aims of this Special Issue on the "Diagnosis of Dementia and Cognitive Impairment" are to present information on promising new approaches to accurately diagnose dementia and cognitive impairment and for the significant differential diagnosis of functional cognitive disorders.

Dr. Andrew J. Larner
Guest Editor

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Keywords

biomarkers
cognitive screening instruments
dementia
diagnosis
imaging
mild cognitive impairment

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

5 pages, 191 KiB

Open AccessEditorial

Diagnosis of Dementia and Cognitive Impairment

by Andrew J. Larner

Diagnostics 2019, 9(4), 180; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9040180 - 07 Nov 2019

Cited by 3 | Viewed by 2713

Abstract

In this special issue of Diagnostics, expert contributors have produced up-to-date research studies and reviews on various topics related to the diagnosis of dementia and cognitive impairment. The methods of the assessments discussed extend from simple neurological signs, which may be elicited in the clinical encounter, through cognitive screening instruments, to sophisticated analyses of neuroimaging and cerebrospinal fluid biomarkers of disease. It is hoped that these various methods may facilitate earlier diagnosis of dementia and its subtypes, and provide differential diagnosis of depression and functional cognitive disorders, as a prelude to meaningful interventions. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

Research

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12 pages, 769 KiB

Open AccessArticle

The Newly Normed SKT Reveals Differences in Neuropsychological Profiles of Patients with MCI, Mild Dementia and Depression

by Hartmut Lehfeld and Mark Stemmler

Diagnostics 2019, 9(4), 163; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9040163 - 25 Oct 2019

Cited by 2 | Viewed by 4104

Abstract

The SKT (Syndrom-Kurztest) is a short cognitive performance test assessing deficits of memory and attention in the sense of speed of information processing. The new standardization of the SKT (2015) aimed at improving its sensitivity for early cognitive decline due to dementia in subjects aged 60 or older. The goal of this article is to demonstrate how the neuropsychological test profile of the SKT can be used to provide valuable information for a differential diagnosis between MCI (mild cognitive impairment), dementia and depression. n = 549 patients attending a memory clinic (Nuremberg, Germany) were diagnosed according to ICD-10 and tested with the SKT. The SKT consists of nine subtests, three for the assessment of memory and six for measuring attention in the sense of speed of information processing. The result of the SKT test procedure is a total score, which indicates the severity of overall cognitive impairment. Besides the summary score, two subscores for memory and attention can be interpreted. Using the level of depression as a covariate, statistical comparisons of SKT test profiles between the three patient groups revealed that depressed patients showed more pronounced deficits than MCI patients in all six attention subtests. On the other hand, MCI patients displayed significantly greater mnestic impairment than the depressed group, which was indicated by significant differences in the memory subscore. MCI and dementia patients showed similar deficit patterns dominated by impairment of memory (delayed recall) with MCI patients demonstrating less overall impairment. In sum, the SKT neuropsychological test profiles provided indicators for a differential diagnosis between MCI and beginning dementia vs. depression. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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6 pages, 227 KiB

Open AccessArticle

Lower CSF Amyloid-Beta_1–42 Predicts a Higher Mortality Rate in Frontotemporal Dementia

by Daniela Vieira, João Durães, Inês Baldeiras, Beatriz Santiago, Diana Duro, Marisa Lima, Maria João Leitão, Miguel Tábuas-Pereira and Isabel Santana

Diagnostics 2019, 9(4), 162; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9040162 - 25 Oct 2019

Cited by 3 | Viewed by 2023

Abstract

Frontotemporal lobar degeneration, the neuropathological substrate of frontotemporal dementia (FTD), is characterized by the deposition of protein aggregates, including tau. Evidence has shown concomitant amyloid pathology in some of these patients, which seems to contribute to a more aggressive disease. Our aim was to evaluate cerebrospinal fluid (CSF) amyloid-beta as a predictor of the mortality of FTD patients. We included 99 patients diagnosed with FTD—both behavioral and language variants—with no associated motor neuron disease, from whom a CSF sample was collected. These patients were followed prospectively in our center, and demographic and clinical data were obtained. The survival analysis was carried through a Cox regression model. Patients who died during follow up had a significantly lower CSF amyloid-beta_1–42 than those who did not. The survival analysis demonstrated that an increased death rate was associated with a lower CSF amyloid-beta_1–42 (HR = 0.999, 95% CI = [0.997, 1.000], p = 0.049). Neither demographic nor clinical variables, nor CSF total tau or p-tau were significantly associated with this endpoint. These results suggest that amyloid deposition in FTD patients may be associated with a higher mortality. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

8 pages, 366 KiB

Open AccessArticle

Functional Cognitive Disorder: Diagnostic Challenges and Future Directions

by Catherine Pennington, Harriet Ball and Marta Swirski

Diagnostics 2019, 9(4), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9040131 - 28 Sep 2019

Cited by 21 | Viewed by 3701

Abstract

Functional cognitive disorder describes patients with persistent, troublesome subjective cognitive complaints that are inconsistent with a recognized disease process, and where significant discrepancies are found between subjective and objectively observed cognitive functioning. The etiology is heterogeneous and potentially related to underlying psychological factors. Making a diagnosis of functional cognitive disorder can be challenging and there is the potential for misdiagnosis of early-stage neurodegeneration. We compared neuropsychological findings in three groups: functional cognitive disorder (FCD), mild cognitive impairment (MCI), and healthy controls. Participants were recruited from the ReMemBr Group Clinic, North Bristol NHS Trust, and via Join Dementia Research. Both the FCD and MCI groups showed elevated prospective and retrospective memory symptom scores. Performance on the Montreal cognitive assessment was equivalent in the FCD and MCI groups, both being impaired compared with the controls. The FCD group was younger than those with MCI. We discuss challenges and controversies in the diagnosis of functional cognitive disorder, alongside illustrative cases and proposals for areas of research priority. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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8 pages, 218 KiB

Open AccessArticle

Triple Test Plus Rapid Cognitive Screening Test: A Combination of Clinical Signs and A Tool for Cognitive Assessment in Older Adults

by Saadet Koc Okudur, Ozge Dokuzlar, Derya Kaya, Pinar Soysal and Ahmet Turan Isik

Diagnostics 2019, 9(3), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9030097 - 15 Aug 2019

Cited by 10 | Viewed by 3468

Abstract

Less time-consuming, easy-to-apply and more reliable cognitive screening tests are essential for use in primary care. The aim of this study was to investigate the diagnostic value of the Turkish version of the Rapid Cognitive Screen (RCS-T) and Triple Test individually and the combination of RCS-T with each sign and Triple Test to screen elderly patients for cognitive impairment (CI). A total of 357 outpatients aged 60 or older, who underwent comprehensive geriatric assessment, were included in the study. Presence or absence of attended alone sign (AAS), head-turning sign, and applause sign was investigated. The mean age of the patients was 74.29 ± 7.46. Of those, 61 patients (28 men, 33 women) had Alzheimer’s disease (AD), 59 patients had mild cognitive impairment (MCI) (29 men, 30 women), and 237 (80 men, 157 women) were cognitively robust. The sensitivity of the combination of RCS-T and negative for AAS for CI, AD and MCI is 0.79, 0.86 and 0.61, respectively; the specificity was 0.92, 0.93 and 0.92, respectively; and the positive and negative predictive values revealed good diagnostic accuracy. The combination of RCS-T and negative for AAS is a simple, effective and rapid way to identify possible CI in older adults. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

12 pages, 965 KiB

Open AccessArticle

Who Is Classified as Untestable on Brief Cognitive Screens in an Acute Stroke Setting?

by Emma Elliott, Bogna A. Drozdowska, Martin Taylor-Rowan, Robert C. Shaw, Gillian Cuthbertson and Terence J. Quinn

Diagnostics 2019, 9(3), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9030095 - 14 Aug 2019

Cited by 16 | Viewed by 4838

Abstract

Full completion of cognitive screening tests can be problematic in the context of a stroke. Our aim was to examine the completion of various brief cognitive screens and explore reasons for untestability. Data were collected from consecutive stroke admissions (May 2016–August 2018). The cognitive assessment was attempted during the first week of admission. Patients were classified as partially untestable (≥1 test item was incomplete) and fully untestable (where assessment was not attempted, and/or no questions answered). We assessed univariate and multivariate associations of test completion with: age (years), sex, stroke severity (National Institutes of Health Stroke Scale (NIHSS)), stroke classification, pre-morbid disability (modified Rankin Scale (mRS)), previous stroke and previous dementia diagnosis. Of 703 patients admitted (mean age: 69.4), 119 (17%) were classified as fully untestable and 58 (8%) were partially untestable. The 4A-test had 100% completion and the clock-draw task had the lowest completion (533/703, 76%). Independent associations with fully untestable status had a higher NIHSS score (odds ratio (OR): 1.18, 95% CI: 1.11–1.26), higher pre-morbid mRS (OR: 1.28, 95% CI: 1.02–1.60) and pre-stroke dementia (OR: 3.35, 95% CI: 1.53–7.32). Overall, a quarter of patients were classified as untestable on the cognitive assessment, with test incompletion related to stroke and non-stroke factors. Clinicians and researchers would benefit from guidance on how to make the best use of incomplete test data. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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17 pages, 2062 KiB

Open AccessArticle

Comparing the Diagnostic Accuracy of Two Cognitive Screening Instruments in Different Dementia Subtypes and Clinical Depression

by Rónán O’Caoimh and D. William Molloy

Diagnostics 2019, 9(3), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9030093 - 08 Aug 2019

Cited by 8 | Viewed by 4394

Abstract

Short but accurate cognitive screening instruments are required in busy clinical practice. Although widely-used, the diagnostic accuracy of the standardised Mini-Mental State Examination (SMMSE) in different dementia subtypes remains poorly characterised. We compared the SMMSE to the Quick Mild Cognitive Impairment (Qmci) screen in patients (n = 3020) pooled from three memory clinic databases in Canada including those with mild cognitive impairment (MCI) and Alzheimer’s, vascular, mixed, frontotemporal, Lewy Body and Parkinson’s dementia, with and without co-morbid depression. Caregivers (n = 875) without cognitive symptoms were included as normal controls. The median age of patients was 77 (Interquartile = ±9) years. Both instruments accurately differentiated cognitive impairment (MCI or dementia) from controls. The SMMSE most accurately differentiated Alzheimer’s (AUC 0.94) and Lewy Body dementia (AUC 0.94) and least accurately identified MCI (AUC 0.73), vascular (AUC 0.74), and Parkinson’s dementia (AUC 0.81). The Qmci had statistically similar or greater accuracy in distinguishing all dementia subtypes but particularly MCI (AUC 0.85). Co-morbid depression affected accuracy in those with MCI. The SMMSE and Qmci have good-excellent accuracy in established dementia. The SMMSE is less suitable in MCI, vascular and Parkinson’s dementia, where alternatives including the Qmci screen may be used. The influence of co-morbid depression on scores merits further investigation. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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9 pages, 751 KiB

Open AccessArticle

Codex (Cognitive Disorders Examination) Decision Tree Modified for the Detection of Dementia and MCI

by Besa Ziso and Andrew J. Larner

Diagnostics 2019, 9(2), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9020058 - 01 Jun 2019

Cited by 7 | Viewed by 4614

Abstract

Many cognitive screening instruments are available to assess patients with cognitive symptoms in whom a diagnosis of dementia or mild cognitive impairment is being considered. Most are quantitative scales with specified cut-off values. In contrast, the cognitive disorders examination or Codex is a two-step decision tree which incorporates components from the Mini-Mental State Examination (MMSE) (three word recall, spatial orientation) along with a simplified clock drawing test to produce categorical outcomes defining the probability of dementia diagnosis and, by implication, directing clinician response (reassurance, monitoring, further investigation, immediate treatment). Codex has been shown to have high sensitivity and specificity for dementia diagnosis but is less sensitive for the diagnosis of mild cognitive impairment (MCI). We examined minor modifications to the Codex decision tree to try to improve its sensitivity for the diagnosis of MCI, based on data extracted from studies of two other cognitive screening instruments, the Montreal Cognitive Assessment and Free-Cog, which are more stringent than MMSE in their tests of delayed recall. Neither modification proved of diagnostic value for mild cognitive impairment. Possible explanations for this failure are considered. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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10 pages, 1390 KiB

Open AccessArticle

MACE for Diagnosis of Dementia and MCI: Examining Cut-Offs and Predictive Values

by Andrew J. Larner

Diagnostics 2019, 9(2), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9020051 - 06 May 2019

Cited by 20 | Viewed by 4591

Abstract

The definition of test cut-offs is a critical determinant of many paired and unitary measures of diagnostic or screening test accuracy, such as sensitivity and specificity, positive and negative predictive values, and correct classification accuracy. Revision of test cut-offs from those defined in index studies is frowned upon as a potential source of bias, seemingly accepting any biases present in the index study, for example related to sample bias. Data from a large pragmatic test accuracy study examining the Mini-Addenbrooke’s Cognitive Examination (MACE) were interrogated to determine optimal test cut-offs for the diagnosis of dementia and mild cognitive impairment (MCI) using either the maximal Youden index or the maximal correct classification accuracy. Receiver operating characteristic (ROC) and precision recall (PR) curves for dementia and MCI were also plotted, and MACE predictive values across a range of disease prevalences were calculated. Optimal cut-offs were found to be a point lower than those defined in the index study. MACE had good metrics for the area under the ROC curve and for the effect size (Cohen’s d) for both dementia and MCI diagnosis, but PR curves suggested the superiority for MCI diagnosis. MACE had high negative predictive value at all prevalences, suggesting that a MACE test score above either cut-off excludes dementia and MCI in any setting. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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Review

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11 pages, 234 KiB

Open AccessReview

Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI): A Review and Update Including Results of Using the TYM Test in a General Neurology Clinic and Using a Telephone Version of the TYM Test

by Jeremy M. Brown, Julie Wiggins, Kate Dawson, Timothy Rittman and James B. Rowe

Diagnostics 2019, 9(3), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9030116 - 08 Sep 2019

Cited by 7 | Viewed by 4954

Abstract

This paper summarises the current status of two novel short cognitive tests (SCT), known as Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI). The history of and recent research on the TYM and TYM-MCI are summarised in applications for Alzheimer’s and non-Alzheimer’s dementia and mild cognitive impairment. The TYM test can be used in a general neurology clinic and can help distinguish patients with Alzheimer’s disease (AD) from those with no neurological cause for their memory complaints. An adapted tele-TYM test administered by telephone to patients produces scores which correlate strongly with the clinic-administered Addenbrookes Cognitive Examination revised (ACE-R) test and can identify patients with dementia. Patients with AD decline on the TYM test at a rate of 3.6–4.1 points/year. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

13 pages, 918 KiB

Open AccessReview

Thirty-Five Years of Computerized Cognitive Assessment of Aging—Where Are We Now?

by Avital Sternin, Alistair Burns and Adrian M. Owen

Diagnostics 2019, 9(3), 114; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9030114 - 06 Sep 2019

Cited by 41 | Viewed by 4764

Abstract

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of ‘meaningful change’ and ‘validity’ indices based on these large norms, more efficient testing, increased sensitivity, and the possibility of characterising cognition in samples drawn from the general population that may contain hundreds of thousands of test scores. The relationship between these new computerized platforms and existing (and commonly used) paper-and-pencil tests is explored, with a particular emphasis on why computerized tests are particularly advantageous for assessing the cognitive changes associated with aging. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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18 pages, 1955 KiB

Open AccessReview

The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer’s Disease—Review of Literature and Interesting Images

by Subapriya Suppiah, Mellanie-Anne Didier and Sobhan Vinjamuri

Diagnostics 2019, 9(2), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics9020065 - 25 Jun 2019

Cited by 69 | Viewed by 7540

Abstract

Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer’s disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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