The cognitive drug research computerized assessment system in the evaluation of early dementia-is speed of the essence?

The cognitive drug research computerized assessment system (COGDRAS) was evaluated in 98 unselected Hammer-smith Hospital Memory Clinic patients (mean age 64.9, range 28-83 years). They were divided into five groups (worried well, depressed, demented, minimally cognitively impaired and other brain disorders) on clinical assessment, Mini Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG) scores. All but one patient completed the computer package, confirming its acceptability. The results of the COGDRAS in the five groups were analysed blind to diagnosis. The performance of the demented group was significantly impaired in comparison with the worried well group, showing that the COGDRAS is valid in mild dementia (mean MMSE 21.5, mean CAMCOG 73.9). The depressed group tended to perform slightly less well than the worried well, and the ‘other’ group showed a wide range of scores consistent with its diversity. The minimally impaired had scores intermediate between the demented and worried well, but an interesting speed/accuracy tradeoff was seen-patients appeared to maintain accuracy by taking longer to perform tasks. The heterogeneity of the minimally impaired group and the role of the measurement of task completion time in the diagnosis of early dementia are discussed.     

Late-onset depression with mild cognitive deficits: electrophysiological evidences for a preclinical dementia syndrome

Mild cognitive impairment (MCI) is present in up to 60% of patients with late-onset depression and constitutes a major diagnostic problem in geriatric psychiatry. Searching for sensitive markers for the detection of early brain changes suggestive of dementia, we compared this depressive risk population with mildly to moderately demented patients and cognitively unimpaired depressed patients using EEG power and coherence. We found a considerable similarity between Alzheimer's disease patients and cognitively impaired depressed patients regarding the cognitive profile and EEG pattern. Changes in EEG power and coherence at frontotemporal leads in depressive patients with MCI thereby allowed discrimination from cognitively unimpaired patients with a sensitivity of 88% and a specifity of 81%.     

Dynamic regulation of EEG power and coherence is lost early and globally in probable DAT

Electroencephalographic (EEG) findings in dementia of Alzheimer type (DAT) include slowing of alpha frequency, loss of alpha band power, increased theta and delta power and reduced coherence. Here it is evaluated whether a) EEG acquisition during different functional states facilitates the detection of DAT-associated EEG changes, and b) EEG changes in mild DAT are topographically confined or global. Power spectra and coherence of EEGs from 29 patients with mild probable DAT and 28 age- and sex-matched controls were compared during three cognitive states. Group differences in power spectra and coherence were largest during resting with eyes open, yielding a 77% correct classification result. Already in early stages of probable DAT, EEG changes were topographically wide-spread. The task-related up- and down-regulation of power and coherence was impaired already in mild probable DAT. We propose to augment clinical EEG assessment by including a quantitative analysis of the dynamic power and coherence changes from rest, eyes closed to eyes open in suspected DAT.     

Neurological abnormalities in cognitively impaired but not demented elderly

OBJECTIVE: We determined the prevalence and clinical characteristics of elderly people with cognitively impaired but not demented (CIND) in the community. MATERIAL AND METHODS: We examined 945 elderly residents (aged 65 years or more) in a cross-sectional study of a standardized clinical examination in 27 randomly selected communities in the town of Mifune, a standard farming town in Japan. RESULTS: The prevalence of CIND and dementia were 10.8% and 4.8%, respectively, with both rates increasing with age. The frequency of most neurological signs in CIND elderly was greater than that found in subjects with no cognitive impairment (NCI) and less than that in subjects with dementia. The mean ADL disability score in CIND subjects also lay between the mean values for those with NCI and those with dementia. There were no differences in lifestyles between the CIND group and the other groups. CONCLUSION: The results suggest that a majority of CIND elderly suffer from brain dysfunction due to chronic neurological disorders or aging itself.     

Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology

OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.     

EEG findings in depressive pseudodementia and dementia with secondary depression

We report EEG findings in 33 elderly patients with mixed symptoms of depression and dementia, followed longitudinally to confirm diagnosis. Two groups of patients, dementia with depressive features (mixed-DEM, group I, n = 23) and patients with depressive pseudodementia (mixed-DEP, group II, n = 10), were defined. In addition, we also included, for comparison purposes, 35 patients with probable AD without depressive features (group III), 23 patients with major depression without cognitive impairment (group IV), and 61 healthy elderly controls (group V). We found significant group differences on waking EEGs between those mixed patients who did well after treatment for depression (depressive pseudodementia) compared to patients having dementia with secondary depression. The differences paralleled those between the 'pure' groups of demented and depressed patients. In patients with either depression or depressive pseudodementia, the EEG was usually normal or showed only mild abnormalities. In contrast, the majority of patients with either dementia or dementia with secondary depression had abnormal EEGs, with approximately one-third having moderate (or severe) abnormalities. Although the EEG was usually normal or only mildly abnormal in patients with pseudodementia or depression, these groups (II and IV) did show a significant slowing of the dominant posterior rhythm compared to controls. They also had a higher percentage of generalized abnormal EEGs than controls and this difference was significant between group IV (depression) and controls.     

First-episode schizophrenics show normal duration and topography of quasistationary EEG segments as compared to controls, during rest as well as during active tasks.

In patients suffering from chronic schizophrenia, both altered temporospatial structure of the EEG and impaired activation during cognitive tasks have repeatedly been demonstrated. The present study evaluates whether similar abnormalities are present in drug-naive first-episode schizophrenics. The EEGs of 32 schizophrenic patients and of 52 healthy controls were recorded during a simple and a complicated motor task, a simple and a complicated auditory stimulus, and during resting periods between the tasks. The temporospatial characteristics were evaluated by adaptive segmentation of EEG, which decomposes an EEG into temporal segments of quasistationary activity. No differences in the temporal and topographic aspects of the EEGs were found between the first-episode schizophrenic patients and the controls, neither during the resting EEGs nor during active tasks. Moreover, the dynamic course of the EEGs, defined as the alternation between task-related changes of temporospatial patterns and the reappearance of resting patterns, was identical in patients and controls. The present findings suggest that while abnormal EEG power spectra seem a consistent finding in treated as well as in never-treated schizophrenics, altered temporospatial patterns and reduced task-related EEG changes are inconsistent signs.     

Correlates of memory function in community-dwelling elderly: the importance of white matter hyperintensities.

We sought to identify magnetic resonance- (MR)-imaged structures associated with declarative memory in a community-dwelling sample of elderly Mexican-American individuals with a spectrum of cognitive decline. Measured structures were the hemispheric volumes of the hippocampus (HC), parahippocampal gyrus, and remaining temporal lobes, as well as severity of white matter signal hyperintensities (WMH). Participants were an imaged subsample from the Sacramento Area Latino Study of Aging (SALSA), N = 122. Individuals were categorized as normal, memory impaired (MI), cognitively impaired non-demented (CIND), or demented. We show that WMH was the strongest structural predictor for performance on a delayed free-recall task (episodic memory) in the entire sample. The association of WMH with delayed recall was most prominent in elderly normals and mildly cognitively impaired individuals with no dementia or impairment of daily function. However, the left HC was associated with verbal delayed recall only in people with dementia. The right HC volume predicted nonverbal semantic-memory performance. We conclude that WMH are an important pathological substrate that affects certain memory functions in normal individuals and those with mild memory loss and discuss how tasks associated with WMH may rely upon frontal lobe function.     

Visual association pathology in preclinical Alzheimer disease

The transition from normal aging to mild cognitive impairment to Alzheimer disease (AD) is often indistinct. Imaging studies suggest early changes in posterior brain regions, including posterior temporoparietal and occipital cortex, but pathologic studies show initial changes in the medial temporal lobe with progressive neocortical involvement as cognition deteriorates. We evaluated the regional distribution of AD pathology in 41 elderly brain donors from the Framingham Heart Study who were cognitively intact, mildly impaired, or demented on the basis of probable AD. We found that 52% of the cognitively intact subjects, and all subjects with mild cognitive impairment or dementia, had dense neurofibrillary tangles (NFTs), neuropil threads, and tau-immunoreactive neurites surrounding neuritic plaques (NPs) in visual association cortex Brodmann area 19. All cognitively intact subjects with area 19 NFTs also had dense core NP and beta amyloid (Abeta) angiopathy in area 19. Area 19 pathology was occasionally present in the absence of substantial pathology in the hippocampus or entorhinal cortex and was not correlated with medial temporal lobe pathology. Dense AD pathology in area 19 is present in some cognitively intact subjects with preclinical AD. The unique metabolic, connectional, and vascular features of this region may confer enhanced vulnerability to neurodegeneration.     

EEG markers of future cognitive performance in the elderly

This exploratory follow-up study investigated whether EEG parameters can predict future cognitive performance. Forty elderly subjects, ranging from cognitively unimpaired to those with Alzheimer disease underwent EEG registration at baseline and neuropsychological examination at both baseline and follow-up. We assessed relations between EEG measures and future cognitive performance (i.e., global cognition, memory, language, and executive functioning) controlling for age, follow-up time, and baseline cognitive performance. Regression models were constructed to predict performance on the Cambridge Cognitive Examination, a widely used tool within dementia screenings. Baseline EEG measures, i.e., increased theta activity (4-8 Hz) during eyes closed and less alpha reactivity (8-13 Hz) during eyes open and memory activation, indicated lower global cognitive, language (trend significant), and executive performance at follow-up. A regression model combining baseline cognitive and EEG measures provided the best prediction of future Cambridge Cognitive Examination performance (93%). EEG and cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG and cognitive measures combined provided the best prediction of future cognitive performance. Although the "cognition only" model showed similar predictive power, the EEG provided significant additional value. The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples.     

Correlations between EEG and CT in 79 cases of dementia

An EEG and CT study was carried out on 79 patients affected by dementia (24 SDAT and 55 MID). The EEG and CT patterns were compared with those of an age-matched control group. Statistical analysis of the CT findings between the demented and normal subjects showed significant differences only for severe atrophy. As far as EEG findings are concerned, no EEG pattern indicative of a specific type of dementia was observed even though a greater number of abnormal EEGs occurred in demented patients than in the control group. Finally, a poor EEG-CT correlation was found in demented patients.     

Cognitive function in UK community-dwelling African Caribbean and white elders: a pilot study

In recent years there has been interest in risk of cognitive impairment and dementia in populations of African origin. Little is known about this risk in older African Caribbean residents in the UK. One difficulty is lack of consensus over an adequate cognitive test battery for this community. Forty-five African Caribbean and 45 age and gender matched white community residents were recruited by household enumeration of an inner London electoral ward. These participants were administered the MMSE during a screening interview. Where possible, this was followed up by tests from the CERAD and CAMCOG neuropsychological batteries, a medical examination, and a structured interview with an informant. Based on these data, a psychiatrist blind to ethnicity independently rated 86 of these participants (41 of the African Caribbeans, all 45 of the whites) as cognitively normal, cognitively impaired, or demented. Of 41 African Caribbeans, 18 (44%) were rated as cognitively normal, 9 (22%) were rated as cognitively impaired, and 14 (34%) were rated as demented. Of the 45 whites, 39 (87%) were rated as cognitively normal, 4 (9%) were rated as cognitively impaired, and 2 (4%) were rated as demented. African Caribbeans scored significantly lower than whites in most cognitive test scores, which was not accounted for by their lower educational and occupational attainment, or their higher frequency of cardiovascular risk factors. African Caribbean elders in the UK appear to be at high risk of cognitive impairment and dementia. However, the influence of potential confounding factors such as socio-economic position and ill-health, and the effect of cultural test bias, cannot be ruled out.     

The Oregon brain aging study: neuropathology accompanying healthy aging in the oldest old

OBJECTIVE: To describe the relationship between neuropathologic aging and longitudinal measures of cognitive function in healthy oldest old individuals. METHODS: Nondemented individuals without cardiovascular or other age-associated diseases of age > or =85 years were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to clinical status, cognitive measures, and rate of cognitive change. RESULTS: Among 19 healthy individuals, 10 became demented or had incipient dementia develop. Clinical status and rate of change in cognitive scores correlated with increasing brain lesion burden, particularly in neocortical regions. Compared to demented individuals, nondemented individuals had few or no neocortical NFT (p = 0.009) or SP (p = 0.001). There was a strong correlation between rate of cognitive change on Mini-Mental State Examination (MMSE) and neocortical NFT (r = 0.859, p = 0.001). The few NFT and SP in nondemented patients had a predilection for limbic areas. CONCLUSIONS: These results support a continuum in which AD is infrequent in the healthy, cognitively stable, oldest old. The minimal abnormalities in cognitively stable individuals are consistent with the notion that preclinical pathologic AD precedes obvious cognitive impairment. Longitudinal cognitive testing shows an increased burden of neuropathologic changes in those who have cognitive decline but are not functionally impaired and do not meet criteria for the diagnosis of dementia. The strong relationship between cumulative pathologic changes and rate of cognitive decline suggests that these lesions may have clinical consequences at any age and are not likely to be benign senescent changes.     

Brain structure and cognition in a community sample of elderly Latinos

BACKGROUND: Previous studies have found that hippocampal atrophy and white matter hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia. The authors measured these variables in a population-based cohort of older Mexican Americans with a wide spectrum of cognitive ability, ranging from normal cognition to dementia. OBJECTIVE: To investigate whether these structural brain changes were seen in individuals prior to the development of dementia and how these changes were related to the presence of dementia. METHODS: A sample of 122 subjects was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired (MI), cognitively impaired but not demented (CIND), and demented. Hippocampal volume was quantified using a region of interest approach. WMH was rated on a semiquantitative scale as the percent of total volume of white matter. RESULTS: Hippocampal volume was significantly reduced in CIND and demented individuals, and WMH were significantly increased in demented subjects. MI subjects did not have any significant changes in hippocampal volume or WMH. The risk for developing dementia was significantly and comparably increased in subjects with either hippocampal atrophy or high WMH. However, the risk for dementia increased dramatically in subjects with both hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in hippocampal volume may be present before dementia but not until cognitive impairment is relatively severe. Because there is a synergistic effect between high WMH and hippocampal atrophy, interactions between vascular and degenerative processes may be important determinants of dementia.     

Resting state oscillatory brain dynamics in Parkinson's disease: an MEG study.

OBJECTIVE: The pathophysiological mechanisms of cognitive dysfunction and dementia in Parkinson's disease (PD) are still poorly understood. Altered resting state oscillatory brain activity may reflect underlying neuropathological changes. The present study using magneto encephalography (MEG) was set up to study differences in the pattern of resting state oscillatory brain activity in groups of demented and non-demented PD patients and healthy, elderly controls. METHODS: The pattern of MEG background oscillatory activity was studied in 13 demented PD patients, 13 non-demented PD patients and 13 healthy controls. Whole head MEG recordings were obtained in the morning in an eyes closed and an eyes open, resting state condition. Relative spectral power was calculated using Fast Fourier Transformation in delta, theta, alpha, beta and gamma frequency bands. RESULTS: In the non-demented PD patients, relative theta power was diffusely increased and beta power concomitantly decreased relative to controls. gamma Power was decreased in central and parietal channels. In the demented PD patients, a diffuse increase in relative delta and to lesser extent theta power and a decrease in relative alpha, beta and to lesser extent gamma power were found in comparison to the non-demented PD group. In addition, reactivity to eye opening was much reduced in the demented PD group. CONCLUSIONS: Parkinson's disease is characterized by a slowing of resting state brain activity involving theta, beta and gamma frequency bands. Dementia in PD is associated with a further slowing of resting state brain activity, additionally involving delta and alpha bands, as well as a reduction in reactivity to eye-opening. SIGNIFICANCE: The differential patterns of slowing of resting state brain activity in demented and non-demented PD patients suggests that, in conjunction with a progression of the pathological changes already present in non-demented patients, additional mechanisms are involved in the development of dementia in PD.     

The cognitive drug research computerized assessment system for demented patients: A validation study

Demeneted elderly patients (N = 23, aged 60–94) and controls (N = 22, aged 52–86) performed a version of the Cognitive Drug Research computerized Assessment System comprising cognitive tasks measuring choice reaction time, vigilance, and the sensitivity and speed of digit, word and picture recognition. The demented patients showed large and highly significant impairments in the speed of choice reaction and in the sensitivity and speed of all memory tasks. Correlations between the various scores from the computerized tests and those from the Folstein Mini-Mental State Examination, the Kendrick Battery and the Kew were high and significant, implying that the computerized tasks measure similar aspects of cognition to procedures used to assess dementia. In 16 memory clinic patients, high correlations were also found between the Stockton Rating Scale and the scores from the computerized tests, suggesting that the latter have relevance to the general behavioural condition of the patients. These findings, together with evidence of good test-retest reliability, indicate that, for demented patients, the utility of this system to assess cognitive change should be comparable to that of previous versions used with the young and with non-demented elderly.     

Mild cognitive impairment in old-age depression is associated with increased EEG slow-wave power

Reversible dementia in geriatric depression is known to be a risk factor for irreversible dementia. Whether just mild cognitive deficits in elderly depressed patients hold a similar risk is not known yet. It may be suggested that elderly depressed patients with mild cognitive deficits, who are prone to develop dementia, show EEG alterations similar to those observed in demented patients. We studied the relationships between cognitive performance, severity of depressive symptoms and quantitative EEG parameters in 31 unmedicated, nondemented, depressed patients aged 60 years or more. Twenty-one of the patients showed a cognitive performance characteristic of mild cognitive impairment. In these patients, the mean delta and theta power was significantly higher than in the patients without cognitive impairment. Total delta power was negatively correlated with cognitive performance. There was no relationship between cognitive performance or EEG parameters and the severity of depression.     

Degree of discrepancy between self and other-reported everyday functioning by cognitive status: dementia, mild cognitive impairment, and healthy elders

BACKGROUND: Previous studies show individuals with dementia overestimate their cognitive and functional abilities compared to reports from caregivers. Few studies have examined whether individuals with Mild Cognitive Impairment (MCI) also tend to underestimate their deficits. In this study we examined whether degree of discrepancy between patient and informant-reported everyday functioning was associated with cognitive status. METHODS: The sample consisted of 111 ethnically diverse community-dwelling older adults (46 Caucasians and 65 Hispanic individuals), which was divided into four diagnostic categories: cognitively normal, MCI-memory impaired, MCI-nonmemory impaired, and demented. Everyday functional abilities were measured using both a self-report and informant-report version of the Daily Function Questionnaire (DFQ). A Difference Score was calculated by subtracting patients' DFQ score from their informants' score. RESULTS: DFQ Difference Scores were significantly higher in the demented group compared to normals and both of the MCI groups. However, the Difference Scores for the MCI groups were not significantly different than the normals. Further, while patient reported everyday functioning did not differ among the four diagnostic groups, informant reported functional status was significantly different across all diagnostic groups except MCI-nonmemory impaired vs normals. Performance on objective memory testing was associated with informant-rated but not patient-rated functional status. Demographic characteristics of the patients and informants, including ethnicity, had no association with the degree of discrepancy between raters. CONCLUSIONS: Although there may be some mild functional changes associated particularly with the MCI-memory impaired subtype, individuals with MCI do not appear to under-report their functional status as can often been seen in persons with dementia.     

EEG mapping during a visuo-spatial task. Averaged maps and group statistics

Twenty young volunteers (10 men, 10 women), righthanded, students, have been recorded in EEG cartography in different situations. We have compared the quantified EEGs when the subjects were resting, eyes closed and later, eyes opened, looking at a cartoon. The EEGs were quantified by spectral Fourier analysis and submitted to data reduction. Ten spectral parameters were computed, yielding 51 variables allowing computations and drawings of 90 EEG maps. Mean parameters, mean variables, averaged EEG maps have been computed for the entire group, between sub-groups, between hemispheres. Non-parametric permutation Fisher tests have been applied for statistical comparisons and statistical validations of the EEG maps computed between subjects. The activation of EEG tracings produced by the opening of the eyes were caracterized topographically by: mean alpha frequencies increased over temporal and rolandic areas; mean alpha amplitudes in microV divided by a factor 3 for occipital areas but unchanged in topography; mean relative amplitudes divided by a factor 2 but with a topography being more parietal than occipital for the alpha rhythm; a resonance coefficient greater over the left parietal than the right (alpha more regular), whereas it was greater over the right occipital than the left during the resting condition. Statistically for the whole group, the left hemisphere, recorded after the right, is more 'activated' in the eyes closed situation. During visual attention, the left hemisphere is less activated than the right.