Severe Stages Of Dementia Research Articles

Electrophysiologic detection of extrapyramidal motor signs in Alzheimer's disease

We applied quantitative methods to measure extrapyramidal signs in 50 Alzheimer's disease (AD) patients and 40 age-matched control subjects. We measured tremor using accelerometers, bradykinesia using computer-detected reaction times (RTs) and movement times (MTs), and rigidity using a strain gauge linked to a movable arm rest. We excluded subjects with a clinical diagnosis of Parkinson's disease and subjects who required antiparkinsonian, neuroleptic, or anxiolytic medications. Aside from rigidity in two patients, there were no extrapyramidal signs on clinical examination. Based on electrophysiologic measures, however, there was a significant increase in muscle tone (p < 0.001), RT (p < 0.01), and MT (p < 0.03) in AD patients as a group compared with control subjects. Within the AD group, muscle tone and MTs increased across clinical stages of dementia severity (p < 0.05). Tremor frequency and amplitude were normal in AD subjects. These data indicate that quantitative neurophysiologic measures are superior to conventional clinical examinations in detecting extrapyramidal signs in AD. The pathologic substrates of extrapyramidal signs in AD are uncertain but seem to be linked to the degenerative AD process.

Multicenter Study of Predictors of Disease Course in Alzheimer Disease (the “Predictors Study”). I. Study Design, Cohort Description, and Intersite Comparisons

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The "Predictors Study," a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.

Interlaboratory Histopathologic Assessment of Alzheimer Neuropathology

Three investigators have applied different histopathologic methods (modified Bielschowsky silver methods, Congo red-gallocyanin) to differentiate Alzheimer's disease (AD) (n = 7 subjects; four with very mild dementia and three with moderate to advanced dementia) neuropathology from brain changes associated with aging in three nondemented individuals who had been evaluated using a validated dementia severity staging instrument [Washington University Clinical Dementia Rating (CDR)] generally within a year of death. The presence of elevated numbers of neocortical (frontal and temporal) diffuse, mature, and total senile plaques (SP) was strongly correlated with the presence of clinical AD but did not equate with CDR dementia severity. Neocortical neurofibrillary tangle (NFT) density as well as hippocampal NFT and SP density in this small series did not differentiate statistically between AD and controls. NFT density appeared to correlate with CDR better than SP density. Quantitative histopathologic assessment of AD markers in only a few brain regions can accurately predict the presence of clinical AD, including the very mild form of the disease. This is especially true for SP in the neocortex.

Intérêt de l'EEG pour la prédiction de l'évolution des démences de type Alzheimer

Twenty patients selected as probable dementia of the Alzheimer type (DAT) have been examined two times during a mean follow-up period of 14.5 months. Two groups have been distinguished at the end of this period: a cognitively impaired one and a stable one. EEG features at T1, at T2 or the difference T1-T2 does not allow an accurate and predictive discrimination between the two groups. But we cannot conclude that EEG is useless for prediction of the rate of progression of the disease in DAT because most of the cognitively stable patients are also stable for mean frequency. So mean frequency could be an interesting marker of evolutivity but this to be tested with more patients including more subjects reaching the severe stage of dementia.

Retrospective Postmortem Dementia Assessment

Neuropathologic studies of dementia and normal aging suffer from a lack of individuals examined for the presence and severity of dementia before death. To increase clinical information in such cases, a retrospective collateral interview was developed. Thirty-nine individuals were studied; 27 had autopsies. In all cases, the autopsy confirmed the Retrospective Collateral Dementia Interview (RCDI) diagnosis of the presence or absence of dementia; the RCDI had a sensitivity of 88% and a specificity of 80% for specifically detecting probable Alzheimer's disease. Agreement between the RCDI and premortem diagnosis was 96%; between RCDI and medical records, 100%. Agreement between RCDI staging of dementia severity and the last assessment of the living subject was 70%; between the RCDI and a brief staging at death, 86%. This validation confirms the value of postmortem interviews with close informants to assess dementia presence and severity.

A Quantitative Analysis of Apraxia in Senile Dementia of the Alzheimer Type: Stage-Related Differences in Prevalence and Type

Apraxia is clinically separable from other cognitive dysfunctions and has the potential to interfere with motor performance in everyday living. To determine its prevalence and severity at each stage of senile dementia of the Alzheimer type (SDAT), a quantitative apraxia battery was used in conjunction with comprehensive quantitative cognitive assessments of 142 SDAT subjects who fell into four stages of dementia severity, and 113 elderly persons determined to be intellectually healthy by the same cognitive assessment. Thirty-five percent of the mildly, 58% of moderately, and 98% of severely demented SDAT subjects showed apraxia. When ideomotor and ideational apraxia were considered separately, ideomotor apraxia was apparent in mild dementia, while ideational apraxia was found only in moderate and severe dementia. When a covariate analysis was employed to test the influence of aphasia that is known to occur in SDAT, ideomotor (but not ideational) deficits were found to be statistically distinct from language impairment. Taken together the findings suggest that ideomotor apraxia may be tied to loss of functional independence in individuals with SDAT.

Advanced Alzheimer's Disease Is a Risk Factor for Late-Onset Seizures

To determine the role of Alzheimer's disease as a causative factor for late-onset epilepsy, 44 subjects with mild senile dementia of the Alzheimer type and 58 healthy control subjects were examined over a 90-month period for the development of focal or generalized seizure activity (excluding myoclonus). At entry, all subjects were free of prior seizures and other neurologic, medical, and psychiatric disorders with the potential to impair cognition. Although no control subject developed seizures during the study period, 7 subjects with senile dementia of the Alzheimer type had at least one documented seizure. All 7 subjects had progressed to the severe stage of dementia by the time of the first seizure. Seizures were generalized tonic-clonic in type and were unassociated with clinical or (in 3 subjects) neuropathologic evidence for epileptogenic factors other than Alzheimer's disease. We conclude that advanced Alzheimer's disease alone may be an important risk factor for new-onset seizures in older adults.

Sleep, EEG and mental function changes in senile dementia of the Alzheimer's type

—Sleep, EEG and mental function variables were studied in 44 subjects diagnosed as having probable senile dementia of the Alzheimer's type (SDAT) and 22 controls matched for age and minimal depression. Results indicate that sleep, EEG and mental function variables all undergo significant change even in the early, mild stage of SDAT, with further change in the moderate and severe stages of dementia. Mental function variables also underwent significant decline across levels of dementia. Sleep and mental function variables had strong power in correctly classifying subjects into control vs. mild dementia groups (90 and 100%, respectively). Dominant occipital rhythm frequency, a clinical EEG measure, also discriminate as well (75%). The results indicate that sleep and EEG variables discriminate well for early, mild SDAT in minimally depressed aged individuals.