Replication of a study of frequency analysis of the resting awake EEG in mild probable Alzheimer's disease.

In the resting EEG, the percentage power in the delta, theta, alpha, and beta bands and the mean frequency were computed in an occipital-vertex derivation for two samples of subjects. The original sample (n = 79) and the new sample (n = 43) each contained a mild probable Alzheimer's disease (SDAT) group and a healthy elderly control group. Group medians in both samples were higher in the SDAT than in the healthy subjects for percentage delta and theta, and were lower for percentage alpha and beta and for mean frequency. Percentage theta and mean frequency were consistent across the two samples in showing statistically significant differences between SDAT and healthy groups. The ability of each EEG measure to detect individual subjects with SDAT was assessed. The most effective measure, percentage theta, had only modest sensitivity (about 20%), but this was attained at a specificity of 100%. The accurate detection of an individual at the mild stage requires that the predictive value of a positive test be high to avoid misclassification of non-SDAT subjects as SDAT. This, in turn, requires a specificity of virtually 100% when the prevalence is low. The low sensitivity puts several constraints on the usefulness of the EEG. For this reason, when the dementia is at the mild stage the EEG would be a useful detector of probable Alzheimer's disease only under certain limiting conditions, including high prevalence, high specificity, and a willingness to accept a high rate of falsely negative tests.     

Paired associate learning in senile dementia of the Alzheimer type

A study was conducted to examine the potential explicit learning ability in senile dementia of the Alzheimer type (SDAT) as a function of (1) the difficulty of the to-be-remembered material and (2) the severity of the dementia. The Associate Learning task from the Wechsler Memory Scale was administered to healthy older adults and individuals with questionable, mild, and moderate SDAT. Individuals with SDAT showed poorer learning performance across trials than healthy older adults. Individuals with questionable and mild SDAT did show evidence for learning across trials for highly related paired associates. For unrelated-paired associates, however, only individuals with questionable SDAT showed some evidence for increased learning across trials.     

Neuropsychological tests as discriminators between dementia of alzheimer type and frontotemporal dementia

The aim of this study was to examine whether cognitive test performance alone could distinguish patients with dementia of Alzheimer type (DAT) from those with frontotemporal dementia (FTD). Scores from three neuropsychological tests were used as discriminating variables in 28 cases with postmortem verified diagnoses. The selected tests measured verbal ability, visuospatial ability and verbal memory. Eighty-nine per cent of the sample was correctly classified by discriminant analysis. Evaluating the ability of the obtained discriminant function to differentiate between groups of DAT and FTD in a new, clinically diagnosed sample of 38 cases yielded an overall success rate of 84%. The results suggest that cognitive tests may be helpful for differential diagnosis in the context of a neuropsychiatric examination.     

Validation of clinical diagnostic criteria for Alzheimer's disease

Clinical investigations of Alzheimer's disease (AD) have been limited by diagnostic inaccuracy. We employed explicit clinical inclusion and exclusion criteria to identify subjects with senile dementia of the Alzheimer type (SDAT). In a consecutive series of 26 postmortem examinations from this sample, AD was histologically verified in all subjects and was the primary dementing illness. Seventeen of the 26 SDAT subjects had been diagnosed when only mildly demented. Two control subjects were examined neuropathologically; AD was absent in both. We conclude that research clinical diagnostic criteria for SDAT, even in its mild stage, are valid.     

Very mild senile dementia of the Alzheimer type. II. Psychometric test performance

A brief battery of psychometric tests was used to compare 41 individuals with very mild senile dementia of the Alzheimer type (SDAT) with 83 healthy participants and 66 individuals with mild SDAT. Although canonical analysis indicated that the same psychological functions (memory, speeded psychomotor performance, and language) are involved in both very mild and mild SDAT, objective levels of performance by the very mildly affected individuals overlapped extensively with those of both healthy aged and mildly demented individuals. Consideration of premorbid individual differences in psychological functions will probably be required if psychometric test performances are to be effective in detecting SDAT in the very mild stage.     

Psychometric differentiation of dementia. Replication and extension of the findings of Storandt and coworkers

In a previous investigation by Storandt and coworkers, a brief battery of four neuropsychological tests was found to accurately distinguish a sample of patients with senile dementia of the Alzheimer type (SDAT) from normal elderly persons. The present study examined the value of these tests in the distinction between SDAT and dementias of other etiologies. Our results replicated those of Storandt and coworkers in that these tests did distinguish normal persons from patients with both SDAT and other dementias. These tests, however, did not accurately differentiate among the dementias. These results indicate that assessment batteries utilizing additional procedures to supplement cognitive testing are indicated to more accurately discriminate among the dementias.     

Blood-brain barrier in Alzheimer dementia and in non-demented elderly

Summary Peroxidase-antiperoxidase staining of formalin-fixed brain was employed to compare the blood-brain barrier (BBB) function in five patients with Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and three patients with AD/SDAT combined with multi-infarct dementia (MID/SDAT) with that of six non-demented aged controls. The diffusion of serum proteins through the BBB was visualized with antisera to albumin, prealbumin, immunoglobulin, C1q, C3c and to fibrinogen. A similar patterns of diffusion was seen in AD/SDAT and non-demented aged individuals. Neuron and glial cells were stained with different antisera in the vicinity of the diffusion. Senile (neuritic) plaques were occasionally visualized with antisera to IgG, C1q and C3c but not with antisera to albumin, prealbumin and fibrinogen in both demented and non-demented aged individuals. Neurofibrillary tangles were not labelled with any of the antisera studied. These results indicate that the BBB is compromised equally in AD/SDAT and in the non-demented elderly.Supported by grants from the Swedish Medical Research Council, King Gustaf V. and Queen Victoria's Foundation, Osterman's, Pfannestill's, Mångberg's and Thuring's foundations and NIH grants NS 18105 and NS 17487     

Alzheimer's dementia produces a loss of discrimination but no increase in rate of memory decay in delayed matching to sample.

Patients diagnosed with senile dementia of the Alzheimer type (SDAT) were compared with control subjects on a computerized delayed matching to sample task. Performance was assessed with a measure of discriminability at zero delay and a measure of rate of forgetting--these are the two parameters of an exponential function derived from extensive animal testing. The SDAT group showed significantly poorer discriminability at zero delay than controls but equivalent rates of forgetting over a 32-sec delay. These data suggest that SDAT may have little effect on the decay rate of the short term (or 'primary') memory trace and may instead affect encoding, initial storage or retrieval mechanisms. The effects of SDAT on this task are consistent with previous results with anticholinergic agents in rats.     

Topographic relationship between neurofibrillary change and acetylcholinesterase rich neurons in the upper brain stem of patients with senile dementia of the Alzheimer's type and Down's syndrome

In order to establish the topographical relationship between neurofibrillary change and the distribution of cholinergic neurons, the upper brain stems were studied from nine cases of senile dementia of the Alzheimer's type (SDAT). For each case, the distribution of the neurofibrillary changes was recorded and compared with the distribution in five control patients of acetylcholinesterase-rich neurons as determined by enzyme histochemistry. The numbers and distribution of neurons with neurofibrillary change were also studied in five age-matched controls and in three individuals with Down's syndrome. The results indicate that, in contrast to that in control patients, the upper brain stem is heavily involved by neurofibrillary change in SDAT. Correlation of the distribution of neurofibrillary tangles in SDAT patients with the localization of acetylcholinesterase-rich neurons suggests that most of the cholinergic nuclei in the upper brain stem are affected in SDAT, but are not exclusively or predominantly involved. Most neurofibrillary tangles were found in noncholinergic nuclei such as the raphe nuclei and the locus ceruleus. The individuals with Down's syndrome showed a heavy involvement in the older cases, thus reinforcing the significance of Down's syndrome in defining the evolution of pathologic changes in Alzheimer's disease or SDAT.     

A longitudinal EEG study of mild senile dementia of Alzheimer type: changes at 1 year and at 2.5 years

This longitudinal study of resting EEGs compared patients with senile dementia of Alzheimer type (SDAT) and healthy controls at 3 times of testing over a 2.5 year period. Measures included the mean EEG frequency as well as the percentage of power in alpha, beta, theta, and delta frequency bands obtained from power spectral analysis. The values from occipital to vertex derivations were averaged for the left and right hemispheres. In healthy older adults delta increased, and both beta and mean frequency decreased over the study period; there was no significant change in theta or alpha. In the SDAT group, all 5 EEG measures changed significantly; there were increases in delta and theta, and decreases in beta, alpha and mean frequency. Theta percentage power distinguished between all 4 stages of dementia (control, mild, moderate and severe). Other EEG measures discriminated only at certain stages. In the mild stage of SDAT theta, beta and mean frequency were already different from control values. In the moderate stage, these differences persisted, and alpha became different. Delta was the last to change, and in the present small sample of those with severe SDAT the difference had not yet reached significance.     

Dementia: characteristics of a referral population and factors associated with progression

We evaluated in a standard fashion 375 patients presenting with complaints of memory loss. Etiology of memory loss included senile dementia of the Alzheimer type (SDAT)-70%, vascular dementia-5%, mixed dementia (SDAT + vascular)-9%, and other etiologies-16%. Incontinence, transient symptoms, and gait disturbances occurred more frequently in vascular dementia than in SDAT. A history of cardiovascular disease and stroke was more common in vascular dementia than SDAT. Disturbances of gait, bradykinesia, and pyramidal tract findings were commonly seen in vascular dementia. Advanced technology aided diagnosis in only 6% of patients and CT was the most useful of such tests. An earlier age of onset was noted in those with a positive family history of SDAT. Duration of symptoms at presentation for SDAT patients varied inversely with the rate of progression of dementia 15 to 55 months later, suggesting that individuals who progress more slowly require more time to elapse before the family or patient realizes the need for medical attention.     

Development and preliminary validation of the First Episode Social Functioning Scale for early psychosis

The current study aimed at developing and conducting a preliminary validation a novel social functioning measure for people with early psychosis. The First Episode Social Functioning Scale (FESFS) was developed to cover many domains specific to this population in their contemporary reality. The self-report version of the FESFS was administered to 203 individuals receiving services in first episode clinics. Scores of the GAF, SOFAS, Social Functioning Scale and BPRS were also obtained for parts of the sample to calculate convergent and discriminant validity. A subgroup also answered the FESFS at several time points during treatment in order to determine sensibility to change. Principal component factor analyses and internal consistency analyses revealed the following nine factors with alphas ranging from 0.63 to 0.80: Friendships and social activities, Independent living skills, Interacting with people, Family, Intimacy, Relationships and social activities at work, Work abilities, Relationships and social activities at school, Educational abilities. Convergent and discriminant validity were demonstrated, as well as sensitivity to change. Clinical and research utility of the FESFS are discussed.     

Senile dementia of the Alzheimer type. Subject attrition and testability in research

There are inherent methodologic problems in investigating senile dementia of the Alzheimer type (SDAT) but this study indicated that, with regard to behavioral test measurement, some of the obvious problems are partially mitigated. First, these data showed that the progressive decline seen in longitudinal SDAT studies is of the same type and magnitude seen in cross-sectional comparisons. Thus, comparing SDAT groups differing in severity provides for the same observations as following up subjects with mild SDAT over time. This study also demonstrates that with certain kinds of tests, selective subject attrition may not be any greater in longitudinal investigations than found in normal aging research. Subjects who dropped out of the longitudinal study were not that different from those who remained in, at least in terms of initial test performance on challenging tests. In this study less than 5% of the subjects with SDAT originally classified as being in the mild stage of the disease remained in this stage after 6 3/4 years of investigation. This inexorable downward path of the subject with SDAT is what appears paramount. Given the similarity of staging in longitudinal and cross-sectional studies, prior test performance levels in the latter studies can be ascertained even if with less accuracy than in longitudinal studies.     

Discriminant validity of a reduced set of Mini-Mental State Examination items for dementia and Alzheimer's disease.

Linear discriminant analysis was used to construct a series of discriminant functions including subsets of demographic variables and Mini-Mental State Examination item responses for a case series and a population sample. A 9-item discriminant function including the variables for time orientation, recall, calculation, copying a figure, age, writing, 3-step command, naming, and race distinguished demented subjects from community controls with 91% sensitivity and 88% specificity. The same discriminant function classified Alzheimer's disease patients and controls with 96% sensitivity and 98% specificity. This discriminant function has been cross-validated as a potential screening instrument for Alzheimer's disease in a community-based sample.     

Nutritional intake in patients with senile dementia of the Alzheimer type.

The dietary intake of 29 healthy controls was compared with that of 35 community-dwelling patients with probable or definite senile dementia of the Alzheimer type (SDAT), based on NINCDS-ADRDA criteria. The control subject or the caregiver of the SDAT patient completed a 3-day estimated-dietary-intake record. Foods offered to patients were chosen, for the most part, by caregivers, but SDAT patients were allowed to eat ad libitum from those choices, and food consumed was recorded. Dietary intake was evaluated against the 1989 Recommended Dietary Allowances (RDA). Dietary intakes did not differ significantly between control and SDAT patients for any of the 32 nutrients analyzed. The controls and SDAT patients met the RDA guidelines for intake of total energy, protein, and micronutrients, with the exception of female SDAT patients, who did not consume a minimum of two thirds of the RDA for vitamin D. All biochemical indices of nutritional status were within normal limits for the SDAT patients. In addition, cognitive function did not correlate with intake of any nutrient studied. We conclude that moderately impaired, community-dwelling patients with SDAT do not differ from healthy controls in nutritional status or nutrient intake. Neither general nor nutrient-specific malnutrition was present in this population. Based on this cross-sectional study, malnutrition does not appear to be a major contributor to the pathogenesis of Alzheimer disease. However, this investigation examined only a single point in time, when patients were being fed by caregivers, so that the role of malnutrition at the beginning of the disease was not addressed.     

Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.     

Serum creatine kinase-BB levels and cerebral cortical creatine kinase activity in senile dementia of the Alzheimer type

A rise in serum creatine kinase-BB (CK-BB) levels has been reported previously in cases of dementia. In the present study the levels of serum CK-BB have been measured in patients clinically assessed to have senile dementia of the Alzheimer's type (SDAT) and in cognitively intact individuals, matched for age, by a specific two-site monoclonal immunoradiometric assay. No significant difference was found between the 2 groups. Total creatine kinase activity in temporal cortex (Brodmann area 21 and 22) was also found to be similar in brains from SDAT or control cases, obtained at autopsy. These results suggest no major change in the permeability of the blood-brain barrier to this enzyme in SDAT patients.     

Senile dementia of Alzheimer type characterized by laminar neuronal loss exclusively in the hippocampus,parahippocampus and medial occipitotemporal cortex

Summary Seven cases of senile dementia of Alzheimer type (SDAT) with unusual clinico-pathological findings are reported. The patients showed neuronal loss in laminar pattern, with gliosis exclusively confined to the CA1 of the hippocampus, the area of the hippocampal gyrus (entorhinal cortex) and medial occipitotemporal cortex. This change was more pronounced in the oral region. The subcortical white matter showed more pronounced fibrillary gliosis than loss of myelin. Both Alzheimer's neurofibrillary tangles and senile plaques were less marked than those usually seen in SDAT. The mental disturbance started after the age of 65 in all patients. The main clinical feature was marked character change in addition to disturbance of cognitive function. Cranial computed tomography showed marked dilatation of the oral portion of the inferior horn of the lateral ventricle in the early stage. It was apparent that although the cases in this group could be incorporated within in the spectrum of SDAT, they could also be considered to represent a variant of SDAT. This group could contribute to an understanding of the clinico-pathological spectrum of SDAT as well as indicating ways of managing such patients.     

Severity and specificity of cognitive impairment in Alzheimer's, Huntington's, and Parkinson's diseases and progressive supranuclear palsy

To investigate differences in severity and specificity of cognitive impairment among various neurodegenerative diseases, we tested groups of patients presenting with senile dementia of the Alzheimer type (SDAT; 44), progressive supranuclear palsy (PSP; 45), Huntington's disease (HD; 35) and Parkinson's disease (PD; 164), with an extensive neuropsychological battery. We found dementia, as defined by a global intellectual performance 2 standard deviations lower than mean control values, in 93% of SDAT, 66% of HD, 58% of PSP, and 18% of PD patients. Specific features of cognitive impairment distinguished the four groups of patients once they were matched for level of intellectual deterioration: remote memory and linguistic disorders in SDAT, frontal lobe-like abnormalities in PSP, concentration and acquisition disorders in HD. There was no specific alteration in demented PD patients. This study demonstrates the frequency of dementia in predominantly subcortical degenerative diseases and indicates that "subcortical dementia," rather than being a homogeneous entity, should be divided into specific subtypes of cognitive impairment related to different underlying specific lesions of each disease.     

Wandering and parietal signs in senile dementia of Alzheimer's type

Among a population of nursing home patients with a diagnosis of senile dementia of Alzheimer's type (SDAT), a subgroup was identified who often became lost and wandered even in familiar surroundings. This subgroup differed from the rest of the SDAT patients on tests of parietal function but not on a generalized test of mental status. Thus, wandering in SDAT patients may be an indication of a specific parietal lobe involvement.