Differential Diagnosis Of Cognitive Impairment Research Articles

Plasma p‐tau181 for the differential diagnosis of cognitive impairment in a prospective, daily clinical practice cohort

AbstractBackgroundCurrently used biomarkers for the differential diagnosis of cognitive impairment are expensive and/or relatively invasive, limiting their availability to the general population. Blood protein biomarkers have showed promising results for screening, differential diagnosis, and prognosis. We aimed to study the diagnostic performance of plasma p‐tau181 in a daily clinical practice, prospective memory clinic cohort.MethodAll patients referred for a first clinical evaluation with suspected cognitive impairment between January 1st, 2020 and March 30th, 2021, were invited to participate in the study. Plasma p‐tau181 was measured using SIMOA technology (Quanterix). Clinical diagnoses were made following current diagnostic criteria and blinded to plasma p‐tau181 results.ResultA total of 232 participants were recruited (mean age 69y, mean MMSE 24), including 25 cognitively unimpaired (CU) controls (mean age 67y, MMSE 28). Clinical diagnoses were AD (82 subjects, 43 of them with prodromal AD [CDR = 0.5]), 83 non‐neurodegenerative cognitive impairment (non‐ND, 75 of them CDR = 0.5), 22 frontotemporal dementia (FTD) and 20 Lewy body disease (LBD).Plasma p‐tau181 levels were statistically higher in AD (mean 2.39 pg/mL) compared with CU (mean 1.09 pg/mL), non‐ND (mean 1.43 pg/mL), FTD (mean 1.69 pg/mL) and LBD (mean 1.64 pg/mL) with a relatively good diagnostic performance for the differential diagnosis between AD and CU, non‐ND, LBD and FTD (AUC of 0.89, 0.80, 0.73 and 0.71, respectively).128 subjects (55% of the cohort) had specific AD biomarkers (CSF or PET) available. In this subgroup, p‐tau181 differentiated AD from CU and non‐ND (AUC 0.91 and 0.92, respectively) and prodromal AD from CDR = 0.5 non‐ND participants (2.32 vs 1.02 pg/mL, p<0.001, AUC 0.90). Plasma p‐tau181 discriminated between a positive and negative amyloid beta status (defined by CSF/PET) with an AUC of 0.87 and AD subjects from those with a clinical diagnosis of LBD and FTD who had a negative amyloid beta status (AUC of 0.94 and 0.86, respectively). Plasma p‐tau181 correlated with CSF p‐tau181 (rs = 0.48, p<0.001).ConclusionIn our cohort of everyday clinical practice, plasma p‐tau181 is an accurate biomarker for predicting the AD pathophysiological process and discriminating AD from other neurodegenerative and non‐neurodegenerative causes of cognitive impairment.

Phonological Verbal Fluency Test for Russian-Speaking Children

Introduction: Verbal fluency tasks are mainly used for assessment of verbal fluency and have proven useful for differential diagnosis. The first objective of the study was to provide normative data on phonemic verbal fluency (for letters “Π” [p], “O” [o], “C” [s]) in children population. The second objective of the study was to establish diagnostic validity of the present task and to collect normative data on participants who survived posterior fossa tumor (PFT) and participants with treated hemoblastosis. Method: For diagnostics, we used verbal fluency test. The normative sample consisted of 746 participants aged 7–16 years. A linear multiple regression analysis was implemented for each dependent variable with age, gender, disease for all participants and academic achievement as predictors in normative sample. The performance of 746 healthy participants was compared to the performance of 118 participants who survived PFT and 492 participants who survived hemoblastosis using one-way ANOVA analysis. Results: Healthy children have better verbal fluency than their peers who survived cancer. In the group of healthy children, we assessed the relationship between verbal fluency and school performance. A significant correlation with the “Russian language” subject (r = 0.127; p < 0.001) emerged. In all three groups of children, age and gender turned out to be significant factors that affected the characteristics of verbal fluency. Conclusion: Our data will contribute to increasing the accuracy of verbal fluency deficit detection in Russian speakers and will be useful for differential diagnosis of cognitive impairment for children who have survived oncological diseases of various geneses.

Clinical Reasoning: Rapidly Progressive Dementia in a Man With HIV Infection and Undetectable Plasma Viral Load.

Neurocognitive decline associated with HIV infection remains prevalent even in the antiretroviral therapy (ART) era, albeit usually in less severe forms. The differential diagnosis of cognitive impairment in this population is quite broad, including infectious causes such as CNS opportunistic infections, causes directly related to HIV such as HIV-associated neurocognitive disorders, and causes entirely unrelated to HIV infection such as primary dementia syndromes. In this case report, a 47-year-old man with HIV on ART with an undetectable plasma viral load presented with rapidly progressive dementia to a clinic in Zambia. He had been functioning independently and fully employed before symptom onset but had to stop working within 2 months of symptom onset because of the severity and rapidity of his cognitive decline. Initial workup led to an empiric diagnosis and initiation of an empiric treatment regimen, which was ultimately ineffective. This prompted re-evaluation, additional workup, and, ultimately, discovering the correct diagnosis. This case highlights the stepwise approach to developing a diagnosis in a resource-limited setting where there exists a high burden of HIV infection, including the necessity of empiric diagnoses of treatment plans when investigations are limited and the importance of reconsidering these diagnoses in the face of additional clinical information. In addition, it highlights both infectious and noninfectious causes of cognitive decline in people with HIV.

Prosody analysis as a tool for differential diagnosis of cognitive impairment

This study was conducted to determine whether acoustic analysis of emotional prosody can assist in differential diagnosis of cognitive impairment. Speech samples describing the Cookie Theft picture were obtained from the Dementia Talkbank and analyzed acoustically. Included in this speech dataset were 10 people with dementia of the Alzheimer’s type, 9 people with mild cognitive impairment, 5 people with vascular dementia, and 10 neurotypical controls. The principal component analysis revealed five factors with two to five acoustic measures per factor for differential diagnosis of cognitive impairment.

Peculiarities of the attention process at depressive disorders

362 patients with cognitive impairment in depressive disorders were examined: 123 patients with recurrent depressive disorder, 141 patients with bipolar affective disorder and 98 people with prolonged depressive reaction. Peculiarities of the process of attention of patients with depressive disorders were the presence of a decrease in concentration, stability and switching of attention, decrease in work efficiency and working capacity. The peculiarities of the functioning of attention indicators were determined for various types of depressive disorders, which can use as diagnostic criteria in the differential diagnosis of cognitive impairment in depressive disorders. Key words: cognitive impairment, depressive disorders, persistence, concentration and switching of attention, recurrent depressive disorder, bipolar depressive disorder, prolonged depressive reaction

CHARACTERISTICS OF COGNITIVE IMPAIRMENT IN PATIENTS WITH DEPRESSIVE DISORDERS

362 patients with cognitive impairment in depressive disorders were examined: 123 patients with recurrent depressive disorder (RDD), 141 patients with bipolar affective disorder (BAD) and 98 people with prolonged depressive reaction (PDR). It was found that cognitive dysfunctions were less pronounced in patients with PDR, than in patients with RDD and BAR (p&lt;0,035). Cognitive dysfunctions in depressive disorders was underlined by the presence of disorders in the mental sphere, in the sphere of attention, executive, visual-spatial and linguistic functions. The differential features of cognitive impairment in patients with RDD, BAR and PDR are highlighted and it should be taken during conducting differential diagnosis of cognitive impairment in depressive disorders. Keywords: patients with cognitive impairment, depressive disorders, cognitive dysfunctions, recurrent depressive disorder, bipolar depressive disorder, prolonged depressive reaction.

Assessment and diagnosis of dementia: a review for primary healthcare professionals.

Dementia is one of the most costly, disabling diseases associated with ageing, yet it remains underdiagnosed in primary care. In this article, we present the comprehensive approach illustrated with a classical case for diagnosing dementia which can be applied by healthcare professionals in primary care. This diagnostic approach includes history taking and physical examination, cognitive testing, informant interviews, neuropsychological testing, neuroimaging, and the utility of cerebrospinal fluid biomarkers. For the differential diagnosis of cognitive impairment, the differences and similarities among normal ageing, mild cognitive impairment, depression, and delirium are highlighted. As primary care physicians are playing an increasingly prominent role in the caring of elderly patients in an ageing population, their role in the diagnosis of dementia should be strengthened in order to provide a quality care for patients with dementia.

Mapping the patterns of cortical thickness in single- and multiple-domain amnestic mild cognitive impairment patients: a pilot study.

Amnestic mild cognitive impairment (aMCI) is considered as a transitional stage between the expected cognitive decline of normal aging and Alzheimer’s disease (AD). Structural brain difference has shown the potential in cognitive related diagnosis, however cortical thickness patterns transferred from aMCI to AD, especially in the subtypes of aMCI, is still unclear. In this study, we investigated the cortical thickness discrepancies among AD, aMCI and normal control (NC) entities, especially for two subtypes of aMCI - multiple-domain aMCI (aMCI-m) and single-domain aMCI (aMCI-s). Both region of interest (ROI)-based and vertex-based statistical strategies were performed for group-level cortical thickness comparison. Spearman correlation was utilized to identify the correlation between cortical thickness and clinical neuropsychological scores. The result demonstrated that there was a significant cortical thickness decreasing tendency in fusiform gyrus from NC to aMCI-s to aMCI-m to finally AD in both left and right hemispheres. Meanwhile, the two subtypes of aMCI showed cortical thickness difference in middle temporal gyrus in left hemisphere. Spearman correlation indicated that neuropsychological scores had significant correlations with entorhinal, inferior temporal and middle temporal gyrus. The findings suggested that cortical thickness might serve as a potential imaging biomarker for the differential diagnosis of cognitive impairment.

18F-FDG PET/CT: an unexpected case of Huntington\u2019s disease

BackgroundHuntington’s disease (HD) is a rare, genetic neurodegenerative disorder often presenting with emotional, cognitive and behavioral abnormalities before manifestation of disease defining motor symptoms. Cognitive impairment is a frequent clinical feature caused by different dementia subtypes. Imaging cortical and subcortical glucose metabolism via 18F-FDG PET/CT can help to discriminate the underlying disease.Case presentationThe patient is a 54-year old man presenting with progressive cognitive impairment and mild orofacial dyskinesia. 18F-FDG PET/CT of the brain revealed a severe bilateral hypometabolism in the striatum. Following imaging Huntington’s disease was suspected and a molecular genetic testing confirmed the diagnosis.ConclusionsHuntington’s disease is a rare but important differential diagnosis of cognitive impairment, especially before motor symptoms are manifest. 18F-FDG PET is capable to show early striatal dysfunction in HD even when structural imaging is normal. We conclude that, in cases with negative family history the HD characteristic metabolic pattern can lead to the diagnosis when no other dementia-suspected changes are present.

Differential Diagnosis of Cognitive Impairment in Bipolar Disorder: A Case Report

In old age bipolar disorder (BD) patients, cognitive complaints difficults an accurate differential diagnosis between cognitive deficits secondary to a primary affective disorder and neurocognitive disorders, such as dementia in Alzheimer’s disease (AD). This case report refers to a female 56-year-old patient with severe and treatment resistant BD type I that presented cognitive decline with loss in recent episodic memory and executive functions in the past year. The diagnosis of mild stage dementia associated to BD was suggested, however neuroimaging tests such as magnetic resonance imaging (MRI) and positron emission tomography with fluordeoxiglicose (PET - FDG) were not enough to exclude the differential diagnosis of AD. The CSF biomarkers (reduced levels of amyloid peptide Aâ1-42 and the elevation of total tau protein and phosphorylated tau levels) resources were decisive for exclusion of an etiological diagnosis of AD.

Combining SPECT and Quantitative EEG Analysis for the Automated Differential Diagnosis of Disorders with Amnestic Symptoms.

Single photon emission computed tomography (SPECT) and Electroencephalography (EEG) have become established tools in routine diagnostics of dementia. We aimed to increase the diagnostic power by combining quantitative markers from SPECT and EEG for differential diagnosis of disorders with amnestic symptoms. We hypothesize that the combination of SPECT with measures of interaction (connectivity) in the EEG yields higher diagnostic accuracy than the single modalities. We examined 39 patients with Alzheimer's dementia (AD), 69 patients with depressive cognitive impairment (DCI), 71 patients with amnestic mild cognitive impairment (aMCI), and 41 patients with amnestic subjective cognitive complaints (aSCC). We calculated 14 measures of interaction from a standard clinical EEG-recording and derived graph-theoretic network measures. From regional brain perfusion measured by 99mTc-hexamethyl-propylene-aminoxime (HMPAO)-SPECT in 46 regions, we calculated relative cerebral perfusion in these patients. Patient groups were classified pairwise with a linear support vector machine. Classification was conducted separately for each biomarker, and then again for each EEG- biomarker combined with SPECT. Combination of SPECT with EEG-biomarkers outperformed single use of SPECT or EEG when classifying aSCC vs. AD (90%), aMCI vs. AD (70%), and AD vs. DCI (100%), while a selection of EEG measures performed best when classifying aSCC vs. aMCI (82%) and aMCI vs. DCI (90%). Only the contrast between aSCC and DCI did not result in above-chance classification accuracy (60%). In general, accuracies were higher when measures of interaction (i.e., connectivity measures) were applied directly than when graph-theoretical measures were derived. We suggest that quantitative analysis of EEG and machine-learning techniques can support differentiating AD, aMCI, aSCC, and DCC, especially when being combined with imaging methods such as SPECT. Quantitative analysis of EEG connectivity could become an integral part for early differential diagnosis of cognitive impairment.

Emerging biomarkers and screening for cognitive frailty.

Physical frailty and cognitive frailty are two important targets of secondary intervention in aging research to narrow the gap between life and health span. The objective of the present narrative review was to examine clinical and epidemiological studies investigating the recently proposed construct of cognitive frailty and its subtypes, with a focus on operational definitions, clinical criteria, and emerging biomarkers potentially useful for the screening of this novel entity. Both physical frailty and frailty indexes with a multidimensional nature were associated with late-life cognitive impairment/decline, incident dementia, Alzheimer's disease (AD), mild cognitive impairment, vascular dementia, non-AD dementias, and AD pathology proposing cognitive frailty as a clinical entity with cognitive impairment related to physical causes with a potential reversibility. The new clinical and research AD criteria established by the National Institute on Aging-Alzheimer's Association and the American Psychiatric Association could improve the differential diagnosis of cognitive impairment within the cognitive frailty construct. The emerging biomarkers of sarcopenia, physical frailty, and cognitive impairment will provide the basis to establish more reliable clinical and research criteria for cognitive frailty, using different operational definitions for frailty and cognitive impairment and useful clinical, biological, and imaging markers for this novel clinical construct.

Clustering and switching during a semantic verbal fluency test contribute to differential diagnosis of cognitive impairment

The verbal fluency test (VFT) can be dissociated into "clustering" (generating words within subcategories) and "switching" (shifting between clusters), which may be valuable in differential diagnosis. In the current study, we investigated the validity of VFT in the differential diagnosis of Alzheimer's disease (AD, n = 65), vascular dementia (VaD, n = 65), mild cognitive impairment (MCI, n = 92), and vascular cognitive impairment without dementia (VCIND, n = 76) relative to cognitively normal senior controls (NC, n = 374). We found that in the NC group, the total correct score was significantly correlated with age and education; males generated more subcategories; cluster size increased with education, and subcategory and switching decreased with age. A significantly progressive advantage was observed in VFT scores in the sequence NC > MCI/VCIND > AD/VaD, and this significantly discriminated dementia patients from the other groups. AD patients performed better in all four VFT scores than VaD patients. Subcategory and switching scores significantly distinguished AD from VaD patients (AD > VaD; mean difference, 0.50 for subcategory, P <0.05; 0.71 for switching, P <0.05). MCI patients scored higher than VCIND patients, but the difference did not reach statistical significance. These results suggest that semantic VFT is useful for the detection of MCI and VCIND, and in the differential diagnosis of cognitive impairment.

Neuronal Ceroid Lipofuscinosis with Early-onset Dementia and Periventricular Leukoencephalopathy in which a Skin Biopsy was Diagnostically Useful

Neuronal ceroid lipofuscinosis (NCL) is a rare disease with onset typically during childhood; however, that developing during adulthood can lead to early-onset dementia. We report a 54-year-old man whose onset coincided with speech impairment, amnesia and dyscalculia. On brain MRI, marked diffuse leukoencephalopathy with periventricular predominance was observed. On a skin biopsy, characteristic fingerprint images were noted, and the patient was diagnosed with NCL. The differential diagnosis of cognitive impairment with leukoencephalopathy is wide ranging; however, when marked symmetrical periventricular-predominant leukoencephalopathy is prevalent and no peripheral neuropathy or gait disorders are evident, a diagnosis of NCL should be suspected and a skin biopsy should be performed.

Clinical applicability of EEG in differential diagnosis of cognitive impairment and dementia

One of the main tasks in the diagnostic work up of cognitive impairment and dementia is to differentiate between the various causes but the current criteria for diagnosis of the most prevalent forms of dementia are of different accuracy and up to 10% of cases are difficult to diagnose with certainty (Knopman DS et al Neurology 2001;56:1143-53.) We present a diagnostic method which can provide support for differential diagnosis into one of the following eight categories: Normal (NRM), Alzheimer's disease (AD), stable Mild Cognitive Impairment (stable for > 24 months = sMCI), Progressive MCI (converting to dementia within 24 months = pMCI), Vascular Dementia (VaD), Lewy-body/Parkinson's (DLBP), depression (DPR) and Frontal Lobe Dementia (FLD). 1050 EEG registrations have been collected into an EEG database. All participants are in the age range of 50 - 90 years. The individuals in the clinical groups were diagnosed at a memory clinic and the NRM individuals were sought from the community. They were not demented and showed no signs of cognitive impairment. Statistical pattern recognition (SPR) was used to create classifiers using selected features from 1120 features of the EEG registration. For all binary comparisons of two distinct groups, a total of 28 comparisons, a numeric index from 0-100 was established to describe the likelihood of an individual belonging to one of the two groups being compared. The diagnostic accuracy of the 28 comparisons all fall within the range 73%-97%. The accuracy is estimated using ten-fold cross validation. Thus it is possible to create a table with the results of the 28 classifications and use it to predict which group a given individual most likely belongs to. Clinical examples illustrate how this technique is applied for differential diagnosis. Following a more substantial clinical validation and an easy access to the methodology, we expect this application of clinical EEG in support for differential diagnosis of dementia to become a realistic first step in the full clinical workup of patients with cognitive impairment and dementia. The underlying technology is well known, widely available and inexpensive in relation to other imaging techniques.

Cognitive Functioning and Aging in Women

SUMMARY Deficits in cognitive function may impact one's ability to attend to stimuli, think clearly, reason, and remember. Impaired cognitive function is a common complaint among older women presenting for treatment in both mental health and medical care settings, and differential diagnosis of type and extent of cognitive impairment is important for appropriate treatment planning and prognosis. Although overall gender differences in prevalence of cognitive dysfunction are minimal, it is important when treating older women to take into account unique challenges they face in the aging process that impact the cause, type and extent of cognitive complaints with which they present in clinical settings. The current paper provides an overview to guide accurate diagnosis, particularly in women, of different types of cognitive impairment under the broad category of dementias, including Alzheimer's, Lewy Body Disease, Vascular Dementia, and due to general medical conditions such as coronary artery bypass surgery, head injury, menopause, hypothyroidism, breast cancer treatment, Fibromyalgia, and chronic fatigue. In addition, emotional factors such as depression in older female patients complicate differential diagnosis of cognitive impairment and must be addressed. Given the multiplicity of causes of cognitive difficulties for women across the life span, careful assessment is crucial; the current paper reviews assessment strategies to prepare an integrated, biopsychosocial strategy for identifying particular cognitive deficits and related psychological and medical problems. In addition, prognostic indicators and treatment planning are discussed to help the practitioner organize an empathic, reasoned and multifaceted treatment approach to maximize recovery, minimize deterioration, and manage symptoms for older women in the context of their social support system and living environment.

Evaluation of the diagnosis and management of cognitive impairment in long-term care.

The objective was to determine the prevalence of screening for cognitive impairment and its effect on diagnosis and management of cognitive impairment in a long-term care setting, especially in comparison to depressive and behavioral symptoms. The study was a prospective cohort study of medical records of 60 patients admitted to the 120 bed Veterans Administration Nursing Home in San Francisco. Screening was determined by documented results on the Mini-Mental Status Examination, Geriatric Depression Scale, and Minimum Data Set. Diagnosis and management were determined by review of medical records for provider documentation. Strategies for management were broad, including interventions such as pharmacological therapy, education, behavioral strategies, or caregiver interventions. Screening was conducted routinely for cognitive impairment (95%), depressive symptoms (95%), and behavioral symptoms (85%). Cognitive status was uncertain in 8 patients; 23 (44%) met criteria for cognitive impairment. Twelve (52%) had a differential diagnosis of cognitive impairment and 11 (48%) had evidence of strategies for management. Depressive and behavioral symptoms were equally or almost as common as cognitive impairment (44% and 25%, respectively), but evidence of a management plan was more frequently present (80% and 100%; p = 0.002 vs. with cognitive impairment). Although depressive and behavioral symptoms were frequently diagnosed and interventions initiated, the diagnosis and management of cognitive impairment were often imprecise or absent. Further research is needed to identify barriers to diagnosis and management so that greater numbers of patients can benefit from recommended strategies.