Evidence of abnormalities in mid-latency auditory evoked responses (MLAER) in cognitive subtypes of patients with schizophrenia.

Abnormalities in measures of mid-latency auditory evoked responses (MLAER) have frequently been reported in schizophrenia, while few studies have examined whether these measures could distinguish cognitive subtypes of schizophrenia. The aim of this study was to investigate whether patterns of performance on MLAER measures could differentiate a cognitive subtype of patients characterized by pervasive cognitive deficits (CD) from patients with only mild cognitive deficits (CS) and controls. An auditory paired-click conditioning test was administered to 55 schizophrenia patients (26 CD, 29 CS) and 49 healthy controls. Amplitudes, latencies and sensory gating indices of the P50, N100, and P200 MLAER were analysed. The results showed that CD patients exhibited smaller S1 amplitudes of N100 and P200 than controls, while CS patients were comparable to controls. Binary logistic regression identified the P200 S1 amplitude as a significant predictor of patients' membership in the CD subtype. However, none of the other MLAER measures could differentiate the two subtypes of schizophrenia. These findings suggest that the abnormal pathophysiologic mechanisms underlying the electrophysiological brain responses to auditory stimulation are associated with the pervasive cognitive deficits, which characterize the CD subtype of schizophrenia. This finding might provide additional electrophysiological endophenotypes for future genetic research of schizophrenia.

Cognitive, affective and behavioural disturbances following vascular thalamic lesions: a review.

During the last decades, many studies have shown that the thalamus is crucially involved in language and cognition. We critically reviewed a study corpus of 465 patients with vascular thalamic lesions published in the literature since 1980. 42 out of 465 (9%) cases with isolated thalamic lesions allowed further neurocognitive analysis. On the neurolinguistic level, fluent output (=31/33; 93.9%), normal to mild impairment of repetition (=33/35; 94.3%), mild dysarthria (=8/9; 88.9%) and normal to mild impairment of auditory comprehension (=27/34; 79.4%) were most commonly found in the group of patients with left and bilateral thalamic lesions. The taxonomic label of thalamic aphasia applied to the majority of the patients with left thalamic damage (=7/11; 63.6%) and to one patient with bithalamic lesions (=1/1). On the neuropsychological level, almost 90% of the left thalamic and bithalamic patient group presented with amnestic problems, executive dysfunctions and behaviour and/or mood alterations. In addition, two thirds (2/3) of the patients with bilateral thalamic damage presented with a typical cluster of neurocognitive disturbances consisting of constructional apraxia, anosognosia, desorientation, global intellectual dysfunctioning, amnesia, and executive dysfunctions associated with behaviour and/or mood alterations. Our study supports the long-standing view of a 'lateralised linguistic thalamus' but restates the issue of a 'lateralised cognitive thalamus'. In addition, critical analysis of the available literature supports the view that aphasia following left or bithalamic damage constitutes a prototypical linguistic syndrome.

Hippocampal volumes, proton magnetic resonance spectroscopy metabolites, and cerebrovascular disease in mild cognitive impairment subtypes.

BACKGROUND: Although a majority of patients with amnestic mild cognitive impairment (aMCI) progress to Alzheimer disease, the natural history of nonamnestic MCI (naMCI) is less clear. Noninvasive imaging surrogates for underlying pathological findings in MCI would be clinically useful for identifying patients who may benefit from disease-specific treatments at the prodromal stage of dementia. OBJECTIVE: To determine the characteristic magnetic resonance imaging (MRI) and proton MR spectroscopy (1H MRS) profiles of MCI subtypes. DESIGN: Case-control study. SETTING: Community-based sample at a tertiary referral center. PATIENTS: Ninety-one patients with single-domain aMCI, 32 patients with multiple-domain aMCI, 20 patients with single- or multiple-domain naMCI, and 100 cognitively normal elderly subjects frequency-matched by age and sex. MAIN OUTCOME MEASURES: Posterior cingulate gyrus 1H MRS metabolite ratios, hippocampal volumes, and cerebrovascular disease on MRI. RESULTS: Patients with single-domain aMCI were characterized by small hippocampal volumes and elevated ratios of myo-inositol to creatine levels. Patients with naMCI on average had normal hippocampal volumes and 1H MRS metabolite ratios, but a greater proportion (3 of 20 patients [15%]) had cortical infarctions compared with patients with single-domain aMCI (6 of 91 [7%]). For characterization of MCI subtypes, 1H MRS and structural MRI findings were complementary. CONCLUSIONS: The MRI and 1H MRS findings in single-domain aMCI are consistent with a pattern similar to that of Alzheimer disease. Absence of this pattern on average in patients with naMCI suggests that cerebrovascular disease and other neurodegenerative diseases may be contributing to the cognitive impairment in many individuals with naMCI.

[Guiding principles of clinical research on mild cognitive impairment (protocol)].

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.

[An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)"].

In order to provide the "guiding principles of clinical research on mild cognitive impairment (MCI) (protocol)" edited by Beijing United Study Group on MCI of the Capital Foundation of Medical Developments (CFMD) with evidence support, clinical criteria, subtypes, inclusion and exclusion of MCI, and use of rating scales were reviewed. The authors suggested that MCI clinical criteria and new diagnosis procedure from the MCI Working Group of the European Alzheimer's disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Diagnostic rating scales including Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Instrumental Activities of Daily Living (IADL) are very useful in definition of MCI but can not replace its clinical criteria. Absence of major repercussions on daily life in patients with MCI was emphasized, but the patients may have minimal impairment in complex IADL. According to their previous research, the authors concluded that highly recommendable neuropsychological scales with cut-off scores in the screening of MCI cases should include Mini-Mental State Examination (MMSE), logistic memory test such as Delayed Story Recall (DSR), executive function test such as Clock Draw Test (CDT), language test such as Verbal Category Fluency Test (VCFT), etc. And finally, the detection of biological and neuroimaging changes, including atrophy in hippocampus or medial temporal lobe in patients with MCI, was introduced.

[Cognitive impairment: classification by proton magnetic resonance spectroscopy and the contributions of conventional magnetic resonance imaging]. / Deterioro cognitivo: clasificación mediante espectroscopia de resonancia magnética de protón y contribución de la imagen convencional.

OBJECTIVE: To analyze the diagnostic accuracy of proton magnetic resonance spectroscopy (1H MRS) in patients with cognitive impairment and to establish the usefulness of complementary information provided by conventional magnetic resonance imaging (MRI). MATERIAL AND METHODS: 64 patients with cognitive impairment, including Alzheimer's disease (AD) (n=31), vascular dementia (n=6), mild cognitive impairment (MCI) (n=9), and major depression (n=18), were studied. All patients underwent cerebral MRI and single-volume 1H MRS using two echo times (TE, 31 and 136 ms) in the posterior cingulate gyrus and right temporal lobe. The metabolites analyzed were N-acetylaspartate (NAA), myo-Inositol (mI), choline (Ch), and creatine (Cr), and the ratios of Ch/Cr, mI/Cr, NAA/mI and NAA/Cr were calculated. In order to differentiate among the different types of cognitive impairment, the alterations in imaging and spectroscopy findings were graded from 0 to 4, as was the mean combination of the two, and then ROC curves were obtained. RESULTS: Statistically significant differences were found between the spectra of patients with dementia (AD and vascular dementia) and those without dementia (MCI and depression) in the posterior cingulate gyrus. The NAA/mI ratio yielded the best area under the ROC curve, with the best sensitivity (82.5%) and specificity (72.7%) in the diagnosis of AD. The NAA/mI and mI/Cr quotients differentiated between the four degenerative pathologies causing the cognitive impairment. The combination of MRI and 1H MRS significantly improved the accuracy of the diagnosis of AD. CONCLUSIONS: The metabolic differences found among patients with cognitive impairment using 1H MRS can be useful for differentiating AD, vascular dementia, MCI, and depression. The combination of spectroscopy and MRI findings is useful in the diagnosis of AD.

The international classification of functioning, disability and health and its application to cognitive disorders.

PURPOSE: This paper describes the conceptual foundation and systematic framework of the International Classification of Functioning, Disability, and Health (ICF) as a mechanism for understanding the course and consequences of various health related states. The specific application of the ICF with persons with cognitive dysfunction is also presented. METHOD: A comprehensive literature review related to the conceptualization of the ICF, its classification scheme and coding process is presented. Information on cognitive disorders including prevalence, functional manifestations and the assessment of a person's cognitive functioning and the applicability of the ICF's holistic classification and coding of cognitive dysfunction within the components of body structure and function, activity and participation, and environmental attributes is also reviewed. CONCLUSION: The ICF has the potential to classify and interpret cognitive deficits on a global level and thereby reflects upon the overall health and functioning of the individual in major life activities. The coding system systematically organizes measures related to the person's cognitive status and the resulting functional outcomes. The ICF focuses on individuals' performance of activities in all aspects of life and validates the independence and well-being of persons with disabilities making it an important instrument to be used by rehabilitation professionals.

Clock drawing: analysis in a retirement community.

OBJECTIVE: To test the hypothesis that performance on a clock-drawing test in a mailed survey to an older cohort is associated with known and potential risk and protective factors for Alzheimer's disease. DESIGN: The Leisure World Cohort Study is an ongoing study, begun in 1981, of nearly 14,000 older adults. In November 1992, the 8,406 living cohort members were mailed a follow-up questionnaire. SETTING: Leisure World Laguna Hills, a southern California retirement community. PARTICIPANTS: The study population is a predominantly white, well-educated, upper-middle-class community; approximately two-thirds are women. Data from 4,843 cohort members (mean age 80 years; range 52-101) were analyzed. MEASUREMENTS: The questionnaire included a clock-drawing task: a predrawn circle 3 1/4 inches (8.3 cm) in diameter was provided with instructions "In the circle below, draw in the numbers as on a clock face. Make no erasures." Clocks were scored on 7 items: all numbers 1-12 present without adding extra or omitting numbers, sequencing of numbers, position of numbers, orientation of numbers to circle, consistent number style (either Arabic or Roman), tilt of numbers, and superfluous marks. A total clock score was calculated by summing the number of correct individual items (0-7). We also classified individuals as cognitively impaired by a previously suggested method: individuals were affected if they did not have three numbers drawn in the upper left quadrant of the clock face. RESULTS: Ninety percent or more of the participants across all ages placed the numbers 1 to 12 on their clocks without omissions or additions; 35% completed the clock drawing without error. The mean total clock scores decreased with each successive 5-year age group in both men and women. Regression analysis indicated a significant effect for age (b = -0.15, P <.0001), education (b = 0.05, P =.0001), smoking (b = 0.13, P =.03), and female gender (b = -0.05, P =.05) and a marginally significant effect of nonrheumatoid arthritis (b = 0.05, P =.07) on total clock score. No other measured variable had a significant effect. Cognitively impaired individuals were more likely to be female and older. After adjusting for age and gender, they were also more likely to be hypertensive and to have taken blood pressure medication and less likely to be college graduates, have glaucoma or arthritis, and to have taken vitamin supplements. CONCLUSION: The clock-drawing task is an appealing measure of cognitive function for large epidemiological studies because it is a simple, self-administered test that is easily adapted to mail surveys and correlates with more-detailed and more-time-consuming cognitive screens. Although it is relatively free of influence by language, cultural, or ethnic factors, our study shows that even in a highly educated population, clock drawing is influenced by educational level and other known risk factors for Alzheimer's disease. Thus a clock-drawing task may help predict cognitive frailty and future disability in older people. Such determination can direct high-risk individuals to earlier diagnosis, potential therapies, and better management.

Effects of relaxing music on agitation during meals among nursing home residents with severe cognitive impairment.

Relaxing music was hypothesized to buffer the general noise level typically found in dining rooms of nursing homes, exert a calming effect, and thus reduce agitated behaviors among residents with severe cognitive impairment. Twenty-nine nursing home residents with severe cognitive deficits participated in a 4-week protocol in which, following baseline observations (week 1), relaxing music was introduced (week 2), removed (week 3), and reintroduced (week 4). Subjects were observed in terms of total number of behaviors of the Cohen-Mansfield Agitation Inventory present during a given week, and the number of behaviors present on the subscales of aggressive, physically nonaggressive, verbally agitated, and hiding/hoarding behaviors. Significant reductions were observed on the cumulative incidence of total agitated behaviors (63.4%); as well as the cumulative incidence of physically nonaggressive behaviors (56.3%) and verbally agitated behaviors (74.5%). No significant reductions were noted in terms of aggressive behaviors and hiding/hoarding behaviors. Where significant reductions were achieved, a distinct pattern was observed. Agitation decreased during week 2, increased again during week 3, only to decrease again in week 4. In addition, variance effects were noted as well, as ranges and standard deviations of agitated behaviors narrowed over time. These findings are interpreted within Hall and Buckwalter's (1988) model of a progressively lowered stress threshold among dementia patients.

A connectionist approach to the prefrontal cortex.

Recent data from studies of the prefrontal cortex (PFC) in humans and laboratory animals are reviewed with particular reference to the anatomical substrates of prefrontal neuropsychological function in health and disease. The PFC has been shown to have a unique pattern of supramodal connectivity with intracortical and subcortical circuits that place the PFC in an anatomical position to subserve "executive" cognitive functions and modulate limbic information to relate to basal ganglia circuits in a highly specific manner and to uniquely control the neurochemical elements of attention and reward. PFC connectivity is also consistent with current hypotheses about prefrontal neuropsychology, which emphasize conscious, goal-directed behavior guided by past experience. PFC connectivity explains the frequency with which prefrontal dysfunction is seen in disease states, which, on the basis of neuroimaging and neuropathology data, can be categorized as either intrinsic or dysconnection disorders.