Cognitive screening in substance users: Diagnostic accuracies of the Mini-Mental State Examination,Addenbrooke’s Cognitive Examination–Revised,and Montreal Cognitive Assessment

Introduction: Despite the considerable prevalence of cognitive impairment in substance-using populations, there has been little investigation of the utility of cognitive screening measures within this context. In the present study the accuracy of three cognitive screening measures in this population was examined—the Mini-Mental State Examination (MMSE), the Addenbrooke’s Cognitive Examination–Revised (ACE–R), and the Montreal Cognitive Assessment (MoCA). Method: A sample of 30 treatment-seeking substance users and 20 healthy individuals living in the community were administered the screening measures and a neuropsychological battery (NPB). Agreement of classification of cognitive impairment by the screening measures and NPB was examined. Results: Results indicated that the ACE–R and MoCA had good discriminative ability in detection of cognitive impairment, with areas under the receiver-operating characteristic (ROC) curve of .85 (95% confidence interval, CI [.75. .94] and .84 (95% CI [.71, .93]) respectively. The MMSE had fair discriminative ability (.78, 95% CI [.65, .93]). The optimal cut-score for the ACE–R was 93 (impairment = score of 92 or less), at which it correctly classified 89% of individuals as cognitively impaired or intact, while the optimal cut-score for the MoCA was <26 or <27 depending on preference for either specificity or sensitivity. The optimal cut-score for the MMSE was <29; however, this had low sensitivity despite good specificity. Conclusions: These findings suggest that the MoCA and ACE–R are both valid and time-efficient screening tools to detect cognitive impairment in the context of substance use.     

The Addenbrooke’s Cognitive Examination-Revised accurately detects cognitive decline in Huntington’s disease

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington’s disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke’s Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington’s disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington’s disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington’s disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington’s disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington’s disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.     

Abhorring the vacuum: use of Alzheimer’s disease medications in frontotemporal dementia

There is no dedicated therapy for frontotemporal dementia (FTD). In order to treat the often devastating behavioral disturbances that interfere with both normal social functioning and the ability of caregivers to provide needed support, off-label medication usage is frequent. In addition to antidepressant and antipsychotic medications, which afford some benefits, US FDA-approved treatments for Alzheimer's disease are often used, including both cholinesterase inhibitors and memantine. Here, we review the various clinical manifestations of FTD, a general approach to treatment and the goals of any potential therapies. We review all of the existing literature on the use of cholinesterase inhibitors and memantine in FTD. While cholinesterase inhibitors do not currently have a place in FTD treatment, memantine may be helpful, although the results of two placebo-controlled trials with this agent are not yet available. Finally, we discuss our view that such approaches will probably become supplanted by rational, molecularly-based therapies currently in development.     

Cognitive dysfunction and dementia in Parkinson’s disease

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder mainly characterized by degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area, in combination with a varying loss of central noradrenergic (locus coeruleus), cholinergic (nucleus basalis of Meynert) and serotonergic (dorsal raphe nuclei) integrity, leading to a multitude of motor and non-motor behavioral disturbances. Apart from the clinical motor hallmarks, in the early stages of disease, subtle cognitive dysfunction might be seen comprising mainly executive dysfunction, with secondary visuospatial and mnemonic disturbances. In about 20-40% of patients, these problems may eventually proceed to dementia, which constitutes an important risk factor for caregiver distress, decreased quality of life and nursing home placement. Dementia in PD is typically characterized by a progressive dysexecutive syndrome with attentional deficits and fluctuating cognition, often accompanied by psychotic symptoms. It is thought to be the result of a combination of both subcortical and cortical changes. PD-related dopaminergic deficiency in the nucleus caudatus and mesocortical areas (due to degeneration of projections from the substantia nigra and ventral tegmental area) and cholinergic deficiency in the cortex (due to degeneration of ascending projections from the nucleus basalis of Meynert), combined with additional Alzheimer-pathology and cortical Lewy bodies, may greatly contribute to dementia.Current treatment of dementia in PD is based on compensation of the profound cholinergic deficiency. Recent studies with the cholinesterase inhibitors galantamine, donepezil and rivastigmine show promising results in improving cognition and ameliorating psychotic symptoms, which must further be confirmed in randomized controlled trials.     

Recalling feature bindings differentiates Alzheimer’s disease from frontotemporal dementia

It has been challenging to identify clinical cognitive markers that can differentiate patients with Alzheimer’s disease (AD) from those with behavioral variant frontotemporal dementia (bvFTD). The short-term memory binding (STMB) test assesses the ability to integrate colors and shapes into unified representations and to hold them temporarily during online performance. The objective of this study is to investigate whether free recall deficits during short-term memory binding (STMB) test can differentiate patients with AD from those with bvFTD and controls. Participants were 32 cognitively intact adults, 35 individuals with AD and 18 with bvFTD. All patients were in the mild dementia stage. Receiver-operating characteristic (ROC) analyses were used to examine the diagnostic accuracy of the STMB. The results showed that AD patients performed significantly worse than controls and bvFTD patients in the STMB test, while the latter groups showed equivalent performance. The bound condition of the STMB test showed an AUC of 0.853, with 84.4% of sensitivity and 80% of specificity to discriminate AD from controls and an AUC of 0.794, with 72.2% of sensitivity and 80% of specificity to differentiate AD from bvFTD. Binding deficits seem specific to AD. The free recall version of the STMB test can be used for clinical purposes and may aid in the differential diagnosis of AD. Findings support the view that the STMB may be a suitable cognitive marker for AD.     

Behavioral and autonomic reactivity to moral dilemmas in frontotemporal dementia versus Alzheimer’s disease

The personal/impersonal distinction of moral decision-making postulates intuitive emotional responses from medial frontal activity and rational evaluation from lateral frontal activity. This model can be analyzed in behavioral variant frontotemporal dementia (bvFTD), a disorder characterized by impaired emotional intuitions, ventromedial prefrontal cortex (vmPFC) involvement, and relative sparing of lateral frontal regions. Moral dilemmas were presented to 10 bvFTD, 11 Alzheimer’s disease (AD), and 9 healthy control (HC) participants while recording skin conductance responses, a measure of emotional arousal. We evaluated their personal versus impersonal conflict, subjective discomfort, and adherence to social norms. Replicating prior work, bvFTD participants were more willing to harm in the personal, but not the impersonal, dilemma compared to AD and HC groups. BvFTD participants had lower arousal and less of an increase in conflict on the personal versus the impersonal dilemma, in contrast to increased arousal and conflict for the AD and HC groups. Furthermore, bvFTD participants verbalized less discomfort, a correlate of low adherence to social norms. These findings support impaired emotional reactions to moral dilemmas in bvFTD and vmPFC lesions and the personal/impersonal model. It suggests a reversion to utilitarian-like considerations when emotional intuition is impaired in the brain.     

Serial position effects rapidly distinguish Alzheimer’s from frontotemporal dementia

Journal of Neurology - A significant proportion of patients with behavioural variant frontotemporal dementia (bvFTD) show memory impairments similar to patients with Alzheimer’s disease (AD),...     

The Addenbrooke’s Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample

The Addenbrooke’s Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20–93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes.     

Can IQCODE detect poststroke dementia?

BACKGROUND: Little is known about the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in the screening of post-stroke dementia (PSDE). METHODS: At 3 months after the index stroke, a research assistant administered the IQCODE to relatives of 189 Chinese patients with acute stroke who were consecutively admitted to a general hospital. A psychiatrist, who was blind to the IQCODE scores, interviewed all 189 patients and made DSM-IV diagnosis of dementia, which served as the benchmark for judging the performance of IQCODE in screening PSDE. RESULTS: The optimal cut-off point of IQCODE was 3.40. The sensitivity, specificity, and positive and negative predictive values of IQCODE, and the area under the receiver operating characteristic curve, were 88%, 75%, 33%, 98%, and 0.88, respectively. CONCLUSIONS: When used as a sole instrument, IQCODE does not appear to be useful in screening PSDE in Chinese elderly.     

Tomm40 polymorphisms in Italian Alzheimer’s disease and frontotemporal dementia patients

Chromosome 19 is one of the several prominent chromosomes related to the risk of developing late-onset Alzheimer’s disease (LOAD) and frontotemporal lobar degeneration (FTLD). However, only Apolipoprotein E (APOE) has been confirmed as a risk factor for both disorders. The aim of this study was to investigate a set of polymorphisms in the translocase of the outer mitochondrial membrane 40 (TOMM40) gene, located in close proximity to APOE, to clarify if the TOMM40 gene may be considered a risk factor for AD and FTLD, independently of APOE status. We performed a case–control study in a dataset of Italian LOAD and FTLD patients, analyzing the following three single-nucleotide polymorphisms (SNPs): rs157580, rs2075650 and rs157581. The analysis was made in 710 Italian subjects: 282 LOAD patients, 156 FTLD patients and 272 healthy subjects. Our results confirm the presence of an association between TOMM40 SNPs and LOAD in our Italian population, suggesting that genetic variations proximate to APOE contributes to the LOAD risk. Genotype and allele distribution of the TOMM40 polymorphisms between the FTLD group and controls did not show any statistical difference. When we analyzed haplotype distribution of the SNPs, taking into account the presence of the APOE allele, we observed a strong association between the ε4 allele and the GAC haplotype both in LOAD and FTLD patients. In contrast, this association did not hold for ε3/GAC. These results demonstrate that the TOMM40 gene does not have an APOE-independent role in the risk of developing LOAD and FTLD.     

CSF metabolites in the differential diagnosis of Alzheimer’s disease from frontal variant of frontotemporal dementia

The early differentiation between Alzheimer's disease (AD) and frontal variant of frontotemporal dementia (fvFTD) is frequently difficult, albeit critical for the adequate management of patients and their caregivers. In order to assess the accuracy of CSF levels of beta-amyloid 1-42 (Aβ), tau (τ) and Thr 181-phosphorilated tau (Pτ) in the early differentiation of AD from fvFTD, we designed a prospective study in which patients have been followed up for at least 2?years. Seventy-two patients with AD and 42 patients with fvFTD showed significantly different CSF levels of Pτ (increased in AD, p?=?0.0001), Aβ (reduced in AD, p?=?0.03), and ratios of Pτ to Aβ (p?=?0.003). ROC analyses showed that the ratio Pτ/Αβ is able to predict diagnosis with an AUC of 0.73 (optimal level being 0.16) corresponding to a sensitivity of 80% and a specificity of 68%. Our findings suggest that CSF metabolites may be the important tools in the early differential diagnosis between AD and fvFTD, albeit to be correlated with clinical, neuropsychological and bio imaging features.     

Schizophrenia and frontotemporal dementia: Shared causation?

Abstract

The relationship between specific genes and particular diseases in neuropsychiatry is unclear, and newer studies focus on shared domains of neurobiological and cognitive pathology across different disorders. This paper reviews the evidence for an association between schizophrenia and frontotemporal dementia, including symptom similarity, familial co-morbidity, and neuroanatomical changes. Genetic as well as epigenetic findings from both schizophrenia and frontotemporal dementia are also discussed. As a result, we introduce the hypothesis of a shared susceptibility for certain subgroups of schizophrenia and frontotemporal dementia. This common causation may involve the same gene(s) at different stages of life: early in schizophrenia and late in frontotemporal dementia. Additionally, we provide a rationale for future research that should emphasize both genetic and cognitive parallels between certain forms of schizophrenia and frontotemporal dementia in a synergistic, coordinated way, placing both in the context of aberrant lateralization patterns.     

Is Cognition Enough to Explain Cognitive Development?

Traditional views separate cognitive processes from sensory–motor processes, seeing cognition as amodal, propositional, and compositional, and thus fundamentally different from the processes that underlie perceiving and acting. These were the ideas on which cognitive science was founded 30 years ago. However, advancing discoveries in neuroscience, cognitive neuroscience, and psychology suggests that cognition may be inseparable from processes of perceiving and acting. From this perspective, this study considers the future of cognitive science with respect to the study of cognitive development.     

Emotion recognition of morphed facial expressions in presymptomatic and symptomatic frontotemporal dementia,and Alzheimer’s dementia

Journal of Neurology - The emotion recognition task (ERT) was developed to overcome shortcomings of static emotion recognition paradigms, by identifying more subtle deficits in emotion recognition...