EEG findings in senile dementia and normal aging

EEG findings in 62 patients with senile dementia of Alzheimer type (SDA), 22 patients with multi-infarct dementia (MID) and 90 controls of same age and sex were studied. The SDA patients differed significantly from the controls in EEG normality, over-all disturbance, dominant occipital rhythm, accentuation of theta and delta, fluctuations in alertness, paroxysmal activity and H-reaction. Even the least severely affected SDA patients differed significantly from the controls in all EEG variables except paroxysmal activity. With increasing degree of intellectual impairment in the SDA group the dominant occipital rhythm became slower.
The MID group differed from the controls in all EEG parameters including asymmetric findings. The EEG findings of the SDA patients differed significantly from those of the MID patients only in asymmetric findings which were more common in the MID patients.
29 % of the normal elderly people had EEG alterations. Abnormalities were mild. Asymmetric findings, mainly theta activity in left temporal region were common. H-reaction (occipital driving response ± 18 c/s) was well preserved in the controls.
EEG is valuable in differentiation of dementia patients from normal elderly people, but differentiation between MID and SDA is not reliable by using EEG, only.     

EEG in the differential diagnosis between Alzheimer''s disease and vascular dementia

Demented patients with Alzheimer's disease (AD) (n = 67), multi-infarct dementia (MID) (n = 77) and probable vascular dementia (PVD) (n = 45) were studied with electroencephalography (EEG). All patients underwent a routine EEG examination and quantitative EEG was recorded from 14 patients with AD, 20 with MID, and 12 with PVD. The patient groups did not differ in regard to sex, age, education, or degree of dementia. Diffuse abnormality of EEG increased in AD, while driving response to photic stimulation and the mean frequency of background activity decreased in all groups with increasing degree of dementia. In quantitative EEG, the percentage of alpha power decreased and those of theta and delta power increased relative to the degree of dementia. Focal abnormalities, and irritative (spikes and/or sharp waves) and slow wave paroxysms were more common in MID than in AD. Patients with different types of dementia did not differ significantly in regard to diffuse abnormality, occurrence of driving response, mean background frequency, or parameters of quantitative EEG. The mean frequency of background activity and the degree of diffuse abnormality correlated with central and cortical atrophy, white matter low attenuation seen on computed tomography, and with neuropsychological findings.     

Erythrocyte glutathione peroxidase and superoxide dismutase in Alzheimer''s disease and other dementias

Activities of 2 enzymes protecting from free radical damage, erythrocyte glutathione peroxidase and superoxide dismutase, were measured in 4 patients with Alzheimer's disease, in 4 with multi-infarct dementia, in 1 with Huntington's disease and in 1 with Hakola-Nasu disease. In none of these dementing diseases the activities were diminished compared to controls.     

Neuropsychological differentiation between normal aging, Alzheimer''s disease and vascular dementia

A random sample of 182 elderly community residents and 211 demented patients were studied using the D-Test Battery based on the Luria's neuropsychological investigation method. A steady but selective cognitive impairment was observed with increasing age in normal healthy subjects. The most sensitive areas of cognition to the effects of normal aging were mnestic and conceptual functions, as well as arithmetical skills. The age-related changes could be clearly differentiated from the changes found in patients with mild degree of dementia. The test also differentiated patients with mild, moderate and severe dementia from each other on the basis of their social competence. It failed to demonstrate specific patterns of impairment and to clearly differentiate between patients with Alzheimer's disease and vascular dementia who had the same degree of cognitive decline. Further qualitative analyses are needed to improve the sensitivity and specificity of the test.     

Plasma cholinesterase activities in dementias,depressions and schizophrenia

Plasma cholinesterase activities were measured in a group of elderly patients and controls. Total cholinesterase activity was found to be decreased to a just significant extent in those suffering from endogenous depression when compared to normal controls. There was a highly significant decrease in cholinesterase activity in the plasma of patients suffering from senile dementia of Alzheimer type (SDAT) but not in those suffering from multi-infarct dementia, neurotic depression or chronic schizophrenia. There was a just significant correlation between total cholinesterase and acetylcholinesterase activity in the plasma of patients suffering from SDAT and the degree of dementia. There were also significant differences between patients with SDAT and MID, and patients with endogenous and reactive depression. The potential use of such tests is discussed.     

Patterns of neuropsychological impairment in mild dementia: a comparison between Alzheimer's disease and multi-infarct dementia

The objective was to investigate the clinical and psychometric differences between patients with dementia of Alzheimer type (DAT) and patients with multi-infarct dementia (MID), matched for age, sex, education, and severity. Sixteen patients with DAT, 16 patients with MID, and 30 healthy individuals, were drawn from a longitudinal study on aging and dementia. Subjects with medical or previous mental disorders were excluded. DAT and controls with focal brain abnormalities on magnetic resonance imaging (MRI) were excluded. Diagnosis of dementia was carried out according to DSM-III-R criteria. Dementia severity was staged using the Clinical Dementia Rating (CDR) scale, and only patients with a score of 0.5-1 on CDR were studied. The main outcome measures were quantitative clinical scales of the assessment of global mental status, depression and anxiety, as well as a wide battery of neuropsychological tests for the evaluation of executive/conceptual functions and memory, as well as attention verbal ability, and visuospatial skill functions. The performance of demented patients compared to normal controls was affected on all measurements except for depression and anxiety. DAT patients showed compared to MID patients a greater extent of impairment on tasks assessing verbal comprehension and memory while MID patients were more significantly impaired on measures of frontal lobe functioning. Clinically matched DAT and MID patients show a differential pattern of neuropsychological impairment when studied in an early stage of dementia and with a mild degree of severity. Such patterns might be of value for the development of clinical diagnostic criteria.     

Survival and cause of death in Alzheimer''s disease and multi-infarct dementia

Survival and causes of death of 218 patients with Alzheimer's disease (AD) and of 115 patients with multi-infarct dementia (MID) were examined. The patients were originally found in a community-based epidemiological survey of dementia, and all patients with AD or MID alive on the prevalence day were included. The 6-years survival rate for AD was 21.1% vs. the expected rate 48.5%, that for MID 11.9% vs. 45.2% expected. A comparison of relative survival rates suggested that MID carries a less favorable survival prognosis than AD. The mean durations were: AD 5.7 years and MID 5.2 years; median duration being 5 years in both diseases. The excess mortality in both AD and MID was independent of age. In AD, the survival rate decreased with increasing severity of dementia, while in MID the mortality was the same regardless of the severity of the dementia. The dementia disorder was the underlying cause of death in 68% of AD patients, and in 38% of MID patients, bronchopneumonia being the most frequent immediate cause of death in both groups. As a cause of death, acute cerebrovascular accidents occurred more often in MID patients than in the general population of comparable age. Malignant diseases were less frequent as a cause of death in both dementia groups than in the general population.     

Frontotemporal degenerative dementias

Frontotemporal dementia (FTD) is a clinical term now used for a group of dementing neurodegenerative disorders marked clinically by general predominance of symptoms referable to the frontal lobes. Symptoms may include changes in language ability with expressive or receptive aphasia, and changes in personality, including disinhibited, obsessive, hyperoral, hypersexual, repetitive, and perseverative behaviors. Memory is often affected, but is usually not a primary symptom. Characteristically, analytic, navigational, and other visuospatial abilities may be quite preserved. The clinical symptomatology of FTD contrasts with the general predominance of temporal and parietal symptoms in the most common neurodegenerative disorder, Alzheimer's disease (AD). FTD symptoms also differ from those seen with the second most common neurodegenerative disorder, Lewy Body Dementia (LBD), which while having substantial clinical and pathological overlap with AD, often shows additional clinical visuospatial (occipital) and parkinsonian symptomatology. FTD likely constitutes the third most-common cause of degenerative dementia. Clinical overlap can sometimes make it difficult to distinguish individual cases from AD. Genetic studies have shown that FTD, like AD, occurs in both familial and nonfamilial types, and a proportion of FTD cases arise from autosomal dominant genetic disorders due to mutations in the tau gene. Some recent formulations include in the family of frontal degenerative disorders other dementias with frontal symptomatology such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Lending support to such a grouping, neuropathological studies show a group of histologies, sometimes including PSP and CBD, to be the substrates for clinical FTD.     

Evaluation of 110 consecutive patients with dementias: a prospective study

We prospectively investigated 131 consecutive cases (both in- and outpatients) of suspected dementia to evaluate the relative frequency of different types of dementia in Chinese patients. Dementia was confirmed in 110 cases (84.0%). In contrast to the Western series, vascular dementia (39.1%) was slightly more frequent than the Alzheimer's disease (36.4%). Twelve cases (10.9%) of potentially treatable dementia were found. Careful clinical observation was the most useful part of the evaluation. CT scan of brain was the most useful laboratory test.     

The "zoom lens" of focal attention in visual search: changes in aging and Alzheimer's disease

Visual search for a target in an array of distractors relies upon flexible shifts between global and local modes of attentional processing. Visual search is slowed in patients with Alzheimer's disease (AD), in part due to an increase in the number and duration of eye fixations made en route to a target (R?sler et al., 2000). This phenomenon may represent a compensatory adaptation to a narrowing of the zone of focal attention, necessitating more shifts of gaze in order to attend to the global workspace. Eye fixations were analyzed in two regions of interest (ROIs, central fixation and peripheral target locations) in 9 patients with mild AD, 9 cognitively intact age-matched control subjects, and 9 young controls, while they searched for a target object in a radial array that contained from 1 to 6 stimuli. Contrasted with young subjects, the search strategy of older controls and, to a greater extent, AD patients showed an increase in the average number and duration of peripheral fixations. Reduced efficiency of visual search in AD may be contributed to by reduced ability to dynamically adjust the attentional zoom, coupled with the inability to disengage attention from peripheral targets.     

Biomarkers in non-Alzheimer dementias

Biomarkers for Alzheimer's Disease (AD) and non-AD dementias could serve as aids to diagnosis and treatment. Biochemical markers have been sought in cerebrospinal fluid (CSF), blood and urine, and are best developed for AD. Ideally, a biomarker should be unique to a dementing disorder and should have high sensitivity. The most widely studied markers for AD, CSF tau and Aβ42, also can show alterations in other disorders. Some non-AD dementias, such as Lewy Body dementia and vascular dementia may be accompanied by AD pathology, making the search for unique markers of these common disorders difficult. However, markers of general pathological processes in neurodegeneration could be used to follow change over time. Prion disorders come closest to having unique biomarkers, although it is difficult to detect the pathogenic Prion proteins (PrPsc) in body fluids. Other protein signatures, such as increased CSF levels of 14-3-3 protein and markedly increased tau have sufficiently high sensitivity and specificity to be used as aids to diagnosis. The development of markers for prion disease stands as a model to drive future research in other dementias.     

Long-term survival and predictors of mortality in Alzheimer's disease and multi-infarct dementia

Long-term survival was examined for 218 patients with Alzheimer's disease (AD) and 115 patients with multi-infarct dementia (MID). The 14-year survival rate for AD was 2.4% versus an expected rate of 16.6%, and for MID 1.7% versus 13.3% expected. MID showed a more malignant natural course than AD. Men carried a less favourable survival prognosis than women, both in AD and MID: the relative risk of dying for women was half that for men in both diseases. In MID, advanced disability indicated a relative risk of dying over twice as high. In both diseases the risk of death was substantially higher in the event of occurrence of primitive reflexes.     

A comparison of brain choline acetyltransferase activity in Alzheimer's disease,multi-infarct dementia,and combined dementia

Summary Brain choline acetyltransferase (ChAT) activity was determined in 43 patients with Alzheimer's disease (AD), 14 with multi-infarct dementia (MID), and 15 with combined dementia (CD) and in 53 age-matched controls. The activity of ChAT declined in the hippocampus, temporal and frontal cortex in patients with AD and CD compared to the controls. In the AD group the reduced activity of ChAT in all brain areas was associated with a greater number of cortical neurofibrillary tangles. The degree of dementia had a negative correlation with the activity of ChAT in the frontal cortex in both AD and CD patients. The activity of ChAT in the temporal cortex of CD patients was negatively associated with the cortical tangle counts. In contrast, the activity of ChAT and MID patients was not essentially different from that of the controls. Neither did the various clinical and neuropathological variables show any significant correlation with ChAT activity in MID patients. Thus, in this study the reduction in the activity of ChAT seems to be associated with Alzheimer-type pathology but not with dementia due to vascular changes.     

A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease

Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles, vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51–82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD.     

Prevalence of moderate and severe Alzheimer dementia and multi-infarct dementia in the population of southeastern Sicily

We have calculate the prevalence rates of moderate and severe dementia of the Alzheimer type (DAT) and of multi-infarct dementia (MID) in a Sicilian population sample aged 40 and over. For DAT the prevalence rate is 0.80% among the over 40s and 2.42% among the over 65s. The prevalence rates for both types, but especially for DAT, increase higher prevalence of primary degenerative dementia among females.

---

Sommario Abbiamo calcolato i tassi di prevalenza della demenza tipo Alzheimer e della demenza multiinfartuale di grado moderato e severo in un campione di popolazione siciliana di 40 anni ed oltre (4337 individui). Per la DAT il tasso di prevalenza è dello 0,80% [LF al 95% 0,56–1,11] nella popolazione di 40 anni ed oltre e diventa pari al 2,42% [LF al 95% 1,69–3,37] nella popolazione che ha raggiunto e superato il 65esimo anno di età.Per la MID la prevalenza è di 0,34% [LF al 95% 0,19–0,56] nella popolazione di 40 anni ed oltre, mentre nella popolazione di 65 anni ed oltre la prevalenza è dello 0,95% [LF al 95% 0,50–1,62].La prevalenza dei due tipi di demenza, e per quella tipo Alzheimer in particolare, aumenta significativamente con l'età. Altrettanto significativa è, sempre per la demenza degenerativa primaria, la più elevata prevalenza nel sesso femminile.

     

Senile plaques do not progressively accumulate with normal aging

Senile plaques (SP) are one of the pathologic hallmarks of Alzheimer's disease (AD). Models of SP formation, particularly the early stages, could provide valuable insight into AD pathogenesis. One such model may be provided by non-demented elderly individuals in whom some SP are a common incidental finding. This study has examined post-mortem brain tissue from a large number of such neurologically normal patients in an attempt to better understand the temporal sequence of SP formation. SP were identified in modified Bielschowsky-stained sections of mesial temporal lobe in 122 (30%) of 402 cases. The prevalence of SP in the temporal neocortex correlated strongly with patient age. Surprisingly, however, neither the mean nor maximum SP density showed any increase with age. This suggests that SP do not progressively accumulate in normal aging but develop over a limited time period after which their number stabilizes at a constant level. In most cases, all SP were of the diffuse type. In 37 cases (9%), however, some neuritic SP (NP) were also seen. Although the NP density did not show a significant increase with age either, the proportion of SP which were neuritic (NP/SP), did. This suggests that changes in SP morphology may be more important than total SP numbers in normal aging.     

Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study.

The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty-two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients.     

Apolipoprotein E polymorphism in various dementias in Taiwan Chinese population

Summary. To verify the association between APOE4 frequency and various dementias in Taiwan Chinese individuals, APOE genotypes were determined in patients with dementia of Alzheimer's type (AD), vascular dementia (VD), dementias due to other general medical conditions (OD), and dementia of Alzheimer's type with cerebral vascular disease (mixed type dementia; MD). Only AD patients exhibited higher APOE4 frequency (OR = 2.95, p = 0.001) than controls after Bonferroni correction to control the overall type I error rate for the multiple testing. No such difference was observed among VD, OD, MD and control groups. The lack of association between VD and APOE4 allele frequency suggests that APOE4 allele does not associate with cerebrovascular pathology related dementia in Taiwan Chinese. Received December 3, 2001; accepted April 9, 2002 Published online July 26, 2002 Acknowledgement This work was supported by Taichung Veterans General Hospital grant TCVGH 894001B. Authors' address: L.-J. Chuo, MD, Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan, e-mail: ljchuo@vghtc.vghtc.gov.tw     

Brain dopamine D-2 receptors in senile dementia

Summary Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of³H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of³H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between³H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.     

Frequency of early and late-onset dementias in a Japanese memory disorders clinic

The aim of this study was to compare the diagnostic profiles of patients with early (age<65 years) and late (age>or=65 years) onset of dementia in a memory disorders clinic in Japan. A total of 512 consecutive memory clinic patients were evaluated using clinical information and results of examinations. Diagnosis of dementia was made according to DSM-III-R, and that of subtypes according to standard diagnostic criteria. A total of 464 patients met the criteria for dementia. Amongst late-onset patients (n=430), Alzheimer's disease (AD) (48.1%) was the most frequent cause of dementia, followed by AD with cerebrovascular disease (CVD) (31.4%), vascular dementia (VaD) (9.1%), dementia with Lewy bodies (DLB) (3.7%), frontotemporal lobar degeneration (FTLD) (1.6%), and others (5.8%). On the contrary, amongst early onset patients (n=34), the most common dementia diagnosis was AD (38.2%), followed by VaD (23.5%), FTLD (14.7%), AD with CVD (5.9%), DLB (2.9%), and others (17.6%). FTLD and VaD were significantly more common in the early onset group. All patients, but one, with DLB and Parkinson's disease dementia were late-onset. The relative frequencies of AD, VaD, and DLB in our series are consistent with epidemiologic findings in several Western countries; however, the frequency of FTLD is not consistent with the previous findings presenting high frequency in late-onset patients in some Western countries.