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Auditory and visual event-related potentials in patients suffering from Alzheimer's dementia and multiinfarct dementia, before and after treatment with piracetam.

We have done a study on 7 subjects suffering from Alzheimer's dementia (AD) and 15 subjects suffering from multiinfarct dementia (MID) to see whether they manifest any changes of amplitudes or latencies concerning event-related potentials (ERP) compared to a group of normal controls and how three months of treatment with piracetam affects those changes. We found that the latencies of all waves are longer in the groups of subjects suffering from AD and MID compared to the normal controls, except for the N100 wave, which showed shorter latency in the AD group. Amplitudes were lower in the groups of patients suffering from AD and MID. These changes were most prominent for the P300 wave. Treatment with piracetam reduced those changes in the precognitive part, though it seemed to have no effect on the cognitive part.

Acoustic Stimulation↗

Discriminative use of SPECT in frontal lobe-type dementia versus (senile) dementia of the Alzheimer's type.

UNLABELLED: Dementia of the Alzheimer's type [(S)DAT] and dementia with frontal features (FLD) are nosological entities with different prognoses and presumed pathophysiology. There is a need for noninvasive differential diagnostic tools. To evaluate whether SPECT perfusion imaging could discriminate between these neurodegenerative disorders, we performed a comparative study. METHODS: SPECT scans using 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) of 21 patients with FLD were compared with those obtained in a group of 19 age- and severity-matched patients suffering from (S)DAT. Brain SPECT perfusion deficits were scored by visual qualitative analysis with respect to location, lateralization and severity. A total severity score of cerebral hypoperfusion (maximal value = 18) was calculated by adding all severity scores (scored between 0 and 3; 0 = no perfusion deficit; 1 = 13%-30% hypoperfusion; 2 = 30%-50%, hypoperfusion and 3 = > 50% hypoperfusion including breaching of the cortex) for right and left frontal, parietal and temporal lobes. Moreover, bifrontal hypoperfusion (Fa) was scored, yielding a value between 0 and 6 by adding the two frontal severity scores. RESULTS: No significant correlation was found between MMSE scores and total severity scores on SPECT. A statistically significant correlation was found between the Middelheim frontality score and frontal severity score. Statistically more significant bilateral hypoperfusion of the parietal lobes was found in the (S)DAT group. Conversely, bifrontal hypoperfusion was found more in the FLD group. Stepwise logistic regression analysis identified the severity of bifrontal hypoperfusion as the most significant contributing parameter to correctly classifying (S)DAT versus FLD on SPECT. The probability of predicting (S)DAT based on the SPECT scan is calculated with the following formula: [equation: see text] Using this equation, a value above 0.5 was predictive for (S)DAT and a calculated value under 0.5 was predictive for FLD. Using this model, 81% of the FLD group and 74% of the (S)DAT were correctly classified. CONCLUSION: Technetium-99m-HMPAO SPECT may help in discriminating FLD from (S)DAT. Bifrontal hypoperfusion was found to be the most powerful predictor of clinical classification. Further validation of the presented logistic regression model is warranted.

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[Evaluation of the level of depression and dementia in patients with primary chronic active epilepsy using the Dementia Mood Assessment Scale].

The study included 40 patients, aged 18-40 years with primary chronic active epilepsy, tested by clinical DMAS scale. We have found that the level of intelectual function damage (dementia) and mood (depression) rates depended on the long duration of epilepsy and the frequency of seizures, less on the frequency of specific EEG findings. Types of epileptic seizures and polytherapy influenced the depression and dementia rates the least in previous epilepsu treatment.

Adolescent↗

Clinical validity of the Mattis Dementia Rating Scale in detecting Dementia of the Alzheimer type. A double cross-validation and application to a community-dwelling sample.

OBJECTIVE: To assess the clinical validity of the Dementia Rating Scale (DRS) in detecting patients with dementia of the Alzheimer type (DAT). BACKGROUND: The DRS is widely used to evaluate cognitive functioning in older adults. Adequate normative data are unavailable; studies addressing the clinical validity of the DRS are limited by small sample sizes. DESIGN AND METHODS: Administered the DRS to 254 outpatients with DAT and 105 healthy elderly subjects. Performed (1) multiple regressions of demographic factors on the DRS and its subscales; (2) derivation of optimal DRS cutoff scores using receiver operating characteristic curves; (3) double cross-validation with stepwise logistic regressions; and (4) application of results to a community-dwelling sample. RESULTS: Age- and education-adjusted DRS scores were computed. The optimal DRS cutoff score for DAT of 129 or less revealed a sensitivity of 98% and a specificity of 97%. The logistic regressions resulted in a combination of the Memory and Initiation/Perseveration subscales that correctly classified 98% of all subjects, 92% of a subsample of 76 patients with mild DAT, and 100% of the 51 patients with autopsy-confirmed DAT. The resultant equation was then applied to a community-dwelling sample (238 healthy elderly subjects and 44 patients with DAT): 91% of patients and 93% of normal subjects were correctly classified. Of an additional 77 individuals with questionable DAT, 43 were classified as demented and 34 were classified as nondemented. CONCLUSIONS: The DRS is a clinically valid psychometric test for the detection of DAT. The Memory and Initiation/Perseveration subscales are its best discriminative indexes for an abbreviated version.

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Subjectively reported sleep quality and excessive daytime somnolence in Parkinson's disease with and without dementia, dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: We compared subjective sleep quality and excessive daytime somnolence (EDS) in controls, Parkinson's disease with (PDD) and without dementia (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We investigated whether sleep dysfunction and EDS associate with motor phenotype in PD, PDD and DLB. METHOD: Assessments included the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). RESULTS: EDS was more frequent in PD, DLB and PDD patients than in AD. PDD, PD and DLB patients also had worse sleep quality when compared with AD and controls. Baseline postural instability-gait difficulty (PIGD) motor phenotype in PDD was associated with a higher ESS score and frequency of EDS, but this association was lost at two years. PSQI scores did not differ between PIGD dominant and non-dominant PD, PDD and DLB patients. CONCLUSION: EDS and poor sleep quality are greater in PD, PDD and DLB, compared with AD. The dissociation of EDS and motor phenotype suggests their pathophysiology is anatomically and/or temporally distinct.

Activities of Daily Living↗

What contribution can the Hachinski Ischemic Scale make to the differential diagnosis between multi-infarct dementia and primary degenerative dementia?

Five research studies in which clinical diagnoses using the Hachinski Ischemic Scale (HIS) underwent neuropathological verification were analysed. These studies reveal that the HIS differentiates between multi-infarct dementia (MID) and dementia of the Alzheimer type (DAT) with only limited accuracy. To some extent, there are considerable differences between the studies as regards the methodology and the patient population. However, there are indications that some items of the ischemic scale clearly distinguish between MID and DAT, whereas others hardly do so or some do not distinguish at all between these two conditions. If the HIS is revised according to the present findings, it can become a more valid differential diagnostic instrument. Such a diagnostic instrument which may be applied without any other technical equipment is required today, since epidemiological data and demographic prognoses show that the prevalence of dementing illnesses will markedly increase in the future.

Journal Article↗

Dexamethasone suppression test in elderly patients with dementia of Alzheimer type, vascular dementia and stroke: a re-evaluation of its applicability.

In order to evaluate the prevalence of non-suppression after dexamethasone in psychogeriatrics and to further verify the reliability of the neurobiological information obtained, dexamethasone suppression test was carried out in a geriatric population composed of patients with dementia of Alzheimer type, vascular dementia, stroke and age and sex-matched controls. Basal cortisol levels did not differ among groups and was positively correlated to age. Prevalence of non-suppression, defined according to Carroll's criterion was high in the pathological groups studied, and relatively high in controls, showing no diagnostic value. Unlikely suppressors, the time course of mean plasma corticol levels of non-suppressors was highly heterogeneous in each group considered, especially in the pathological groups. More restrictive criteria for the definition of non-suppressors are proposed, in order to increase the specificity of the test when applied to psychogeriatrics.

Journal Article↗

Patterns of neuropsychological impairment in dementia of the Alzheimer type and multi-infarct dementia.

Patterns of performance on 22 neuropsychological tests were examined in 58 patients with presumed dementia of the Alzheimer type (DAT) and 58 patients with presumed multi-infarct dementia (MID). Few differences between patterns of performance in DAT and MID were found when overall level of performance was taken into account. Within the DAT group, there were some age-related differences in performance that in themselves might support other studies suggesting clinical and neuropathological differences between subtypes of DAT that are related in part to the age at which the condition occurs. However, similar age-related patterns were found in the MID group and the DAT and MID groups did not differ significantly in this respect. Considerable inter-individual variability in pattern of performance was apparent within each group. A proportion of patients were re-assessed 10 months after initial assessment: the extent of decline over time was not predictable from patients' characteristics or test performances at initial assessment. 'De-differentiation' in patterns of impairment, over time or with increasing severity of impairment, was not observed.

Journal Article↗

Topography of the quantitative electroencephalogram in dementia of the Alzheimer type: relation to severity of dementia.

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients.

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Consensus paper of the WFSBP Task Force on Biological Markers of Dementia: the role of CSF and blood analysis in the early and differential diagnosis of dementia.

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Abeta peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.

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Autobiographical memory in normal aging and primary degenerative dementia (dementia of Alzheimer type).

Autobiographical memory of old people (71-89 years) was studied by a method of free narratives, with normal subjects as well as patients with primary degenerative dementia (SDAT) at three stages of development. The chronological distribution of memories across the life span in both groups showed a peak in adolescence and early adulthood, decrease in mid-life, and increase in recent years. This distribution is different from the results found with the prompt word method among normal old adults, but is similar to the chronological pattern reported for vivid memories. The distribution in the demented group was more flat, which contradicts theories of selective preservation of early memories. With the progression of dementia, autobiographical memory deficits were first evidenced by inaccessibility or loss of memories, and, at a later stage, by loss of details of the retrieved memories and impairment of temporal structure. Events that marked transitions in the lives of the patients ("landmarks") were less subject to forgetting than nontransitional events. The article argues for an approach to autobiographical memory that takes into account sociocultural and developmental determinants of memorability as well as internal mechanisms of the cognitive system.

Aged↗

Alzheimer's presenile dementia, senile dementia of Alzheimer type and Down's syndrome in middle age form an age related continuum of pathological changes.

A loss of nerve cells from the nucleus basalis of Meynert and the locus caeruleus together with a reduction in nucleolar volume in surviving cells was measured in twenty-two patients with Alzheimer's disease who ranged in age from 48-92 years, and in six patients over 50 years of age with Down's syndrome who also showed extensive formation of senile plaques and neurofibrillary tangles within their cerebral cortex. When compared with age matched controls the severity of these changes was greatest in the younger patients with Alzheimer's disease, but this fell with age such that by 90 years the level of change in Alzheimer's disease approached that in old age alone. There were only slight differences in the extent of these pathological changes in those patients with Down's syndrome when compared with others of similar age with Alzheimer's disease. It is concluded that the presenile dementia of Alzheimer's disease, the senile dementia of Alzheimer type and Down's syndrome in middle age all form an age-related continuum of pathological change.

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Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle-only dementia): the Hisayama Study.

Senile dementia of the neurofibrillary tangle type (SD-NFT) is characterized by numerous neurofibrillary tangles (NFT) in the hippocampal region and the absence or minimal presence of senile plaques throughout the brain. We analyzed 207 demented subjects and 68 non-demented subjects autopsied in the Hisayama study to investigate the clinicopathological aspects of SD-NFF in the general Japanese population. The prevalence of SD-NFT in the consecutive autopsy cases was 8/207 (3.9%), comprising three men and five women. The average age at onset and death was 83.8 +/- 6.8 (mean +/- SD; standard deviation) and 88.1 +/- 7.6 years, respectively. A mild memory disturbance preceded a decrease in the ability to undertake the activities of daily living and the diagnosis of dementia. Focal cerebral symptoms, such as aphasia and paralysis, did not appear during the disease course of any subject. Gross examination of the brains showed moderate to severe diffuse cerebral atrophy with brain weight loss (mean +/- SD; standard deviation: 1118.1 +/- 124.0 g). Histologically, there were abundant NFT and neuropil threads predominantly in or limited to the limbic cortex. The density of NFT in the CA1/subiculum in SD-NFT was much higher than the densities in the other hippocampal regions. The average density of NFT in CA1 in SD-NFT subjects was 115.4 per 100 x field (range 23-247), that in Alzheimer disease (AD) subjects was 80.1 (range 1-227), and that in non-demented elderly subjects was 37.2 (range 0-203). Although many previous papers have reported that the densities of NFT in the limbic system in SD-NFT were significantly higher than those in AD, there was considerable overlap of NFT densities in CA1 among the non-demented elderly, AD subjects and SD-NFT subjects.

Aged↗

Cognitive and motor symptoms in dementia: focus on dementia with Lewy bodies.

PURPOSE: To describe the clinical syndrome called dementia with Lewy bodies (DLB) and highlight its common and unique characteristics with respect to diagnosis and management. DATA SOURCES: Review of the scientific literature including psychiatric literature, reports of clinical trials, and clinical practice guidelines. CONCLUSIONS: DLB is a clinical and histopathologic disease, which is second only to Alzheimer's disease (AD) as a cause of dementia in older adults. The clinical syndrome of DLB includes cognitive and motor deterioration reminiscent of symptoms associated with AD and Parkinson's disease (PD) respectively. IMPLICATIONS FOR PRACTICE: The late life intersection of cognitive and motor symptoms can present significant challenges in the primary care setting. Recognizing key features of common neurodegenerative disorders is essential to accurately diagnosing and appropriately treating the growing population of older adults who suffer from AD, PD, and DLB.

Alzheimer Disease↗

Disturbance of sensory filtering in dementia with Lewy bodies: comparison with Parkinson's disease dementia and Alzheimer's disease.

INTRODUCTION: Prepulse inhibition (PPI) is considered to mirror an organism's ability to filter out irrelevant sensory or cognitive information. The disruption of PPI has never been studied in individuals suffering from dementia with Lewy bodies (DLB). As attention deficits largely contribute to cognitive impairment in DLB, an investigation with a PPI paradigm is useful for differential diagnosis of DLB versus Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). OBJECTIVE AND METHODS: PPI of the N1/P2 component of auditory evoked potentials was used to investigate the early stages of attention selectivity in 10 DLB, 10 AD, and 10 PDD patients, as well as in 10 healthy controls. The PPI paradigm consisted of the presentation of sound pulses (40 ms, 115 dB) preceded by a prepulse (40 ms, 80 dB). Sound stimuli were presented in a total of 80 trials in a pseudo-random order. RESULTS: Non-parametric analyses of variance revealed a significant group effect on the 120 ms lead interval. Retrospective analyses revealed that PPI was significantly reduced in DLB compared to healthy controls and AD. In the PDD group, the disturbance was of intermediate intensity. CONCLUSION: The present study revealed a severe disturbance of PPI in DLB patients. The DLB patients displayed a specific disruption profile in terms of magnitude as well as time course.

Acoustic Stimulation↗

Higher cortical deficits influence attentional processing in dementia with Lewy bodies, relative to patients with dementia of the Alzheimer's type and controls.

BACKGROUND: Attentional dysfunction is believed to be a prominent and distinguishing neuropsychological feature of dementia with Lewy bodies (DLB); yet, the specific nature of the attentional deficit and factors that can potentially influence attentional processing in DLB have not been fully defined. AIMS: To clarify the nature of the attentional deficit in early-stage DLB relative to patients with early-stage dementia of the Alzheimer's type (DAT) and elderly controls, and examine the effect of task complexity and type of cognitive load on attentional processing in DLB. METHODS: Attentional impairment and fluctuating attention were investigated in three groups of subjects--patients with clinical features of early probable DLB (n = 20), a group with early probable DAT (n = 19) and healthy elderly controls (n = 20)--using an experimental computerised reaction time paradigm. RESULTS: Patients with DLB showed greater attentional impairment and fluctuations in attention relative to patients with DAT and elderly controls. The attentional deficit was generalised in nature but increased in magnitude as greater demands were placed on attentional selectivity. Attentional deficits in DLB were most pronounced under task conditions that required more active recruitment of executive control and visuospatial cognitive processes. CONCLUSIONS: Attentional deficits in DLB are widespread and encompass all aspects of attentional function. Deficits in higher cortical function influence the degree of attentional impairment and fluctuating attention, suggesting that attentional processing in DLB is mediated by interacting cortical and subcortical mechanisms. These findings serve to clarify the nature of the attentional deficit in DLB and have potentially important ramifications for our understanding of the neurocognitive underpinnings of fluctuations.

Aged↗

Comparison of executive and visuospatial memory function in Huntington's disease and dementia of Alzheimer type matched for degree of dementia.

Groups of patients with Hungington's disease and probable dementia of Alzheimer type (DAT) matched for level of dementia on the basis of mini mental state examination scores were compared in several tests of visual memory and tests sensitive to frontal lobe dysfunction. Whereas recall of patients with DAT tended to be worse on the Kendrick object learning test, the two groups were equivalent on tests of sensorimotor ability and delayed matching to sample performance. By contrast, the patients with Huntington's disease were significantly worse on tests of pattern and spatial recognition, simultaneous matching to sample, visuospatial paired associates, and on three tests sensitive to frontal lobe dysfunction--namely, the Tower of London test of planning, spatial working memory, and a visual discrimination learning and reversal paradigm. The impairments in these tests, however, did not always qualitatively resemble those seen in patients with frontal lobe damage and may be more characteristic of primary neostriatal deficit. In the visual discrimination paradigm the patients with Hungtington's disease were significantly worse than the patients with DAT at the simple reversal stage, where they displayed significant preservation to the previously rewarded alternative. The results are consistent with the hypothesis that patients with Huntington's disease exhibit deficits in tests sensitive to frontostriatal dysfunction and that this form of intellectual deterioration is qualitatively distinct from that seen in Alzheimer's disease.

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