G. J. M. Walstra

The diagnostic value of electroencephalography in mild senile Alzheimer's disease

OBJECTIVEnWe investigated the diagnostic value of the visually assessed electroencephalogram (EEG) in patients with mild Alzheimers disease (AD), using the grand total of EEG (GTE) score.nnnMETHODSnForty-nine non-demented control subjects with and without minimal cognitive impairment from the general population and 86 probable AD patients (NINCDS-ADRDA criteria), consecutively referred to a memory clinic, participated in this study.nnnRESULTSnFrequency of rhythmic background activity (P<0.05), diffuse slow activity (P<0.001), and reactivity of the rhythmic background activity (P<0.001) were statistically significant related to the diagnosis control subject or AD patient, using logistic regression analysis with adjustment for age and sex. When these subscores were used to confirm the diagnosis of AD, thus at high specificity of 89.1% (GTE cut-off point of 3), the sensitivity was 44.6% and positive predictive value was 88.1%. Incremental ruling-in and ruling-out curves showed a maximum diagnostic gain of 38% for a positive test result at a prior probability ranging from 30 to 40%. At high pretest probability levels of 80-90%, the diagnostic gain for a positive test result was low, varying from 7 to 14%.nnnCONCLUSIONnIn conclusion, the visually assessed EEG may give a clinically meaningful contribution to the diagnostic evaluation of AD when there is diagnostic doubt.

Early detection of Alzheimer's disease using the Cambridge Cognitive Examination (CAMCOG).

BACKGROUNDnDementia screening instruments, such as the Cambridge Cognitive Examination (CAMCOG), measure a variety of cognitive functions. However, memory impairment generally is the first sign of Alzheimers disease (AD). It seems logical, therefore, to use only memory-related items for the early detection of AD. We divided the CAMCOG into a memory section and a non-memory section, and tested the hypothesis that the memory section predicts AD better than the non-memory section. We also provide normative data for both sections.nnnMETHODSnNormal subjects (N = 169) and patients with incident AD (i.e. satisfying AD criteria between 1 and 3 years from baseline: N = 25) were participants in the Amsterdam Study of the Elderly (AMSTEL), a population-based longitudinal study on cognitive decline and dementia. Patients with prevalent AD (i.e. satisfying AD criteria at baseline: N = 155) were either recruited in a memory clinic or came from AMSTEL. Normal subjects were cognitively intact at baseline and remained so for at least 3 years. The CAMCOG was administered to all subjects. AD was diagnosed by DSM-III-R criteria.nnnRESULTSnLogistic regression analysis showed that the memory section was related to prevalent AD, whereas in multivariate analysis the non-memory section was not (after correction for the memory score and demographic characteristics). A similar analysis showed that the memory section predicted incident AD, as did a higher score on the non-memory section. The MMSE did not predict incident AD better than age alone.nnnCONCLUSIONnFor the early detection of AD it is best to use the memory and non-memory sections separately instead of the total CAMCOG score.

Determinants of Quantitative Spectral Electroencephalography in Early Alzheimer’s Disease: Cognitive Function, Regional Cerebral Blood Flow, and Computed Tomography

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer’s disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

Early diagnosis of dementia: which tests are indicated? What are their costs?

Abstract Dementia is reversible in a minority of patients, and these should be diagnosed but without subjecting the majority with irreversible disease to an excessive set of investigations. Should a battery of ancillary investigations be performed routinely in dementia? Or can these tests be carried out as clinically indicated? Three arguments are important to answer this question. (a) Reversible dementia is rare: about 1% of cases. (b) If the clinical criteria for diagnosing primary degenerative disease are used consistently, the results of investigations can be predicted with sufficient accuracy, except those of blood tests. (c) Treatment of reversible dementia has the best results in its most frequent causes: depression and drug intoxication; however, treatment of medical and surgical causes of dementia may also be effective. Based on these three considerations, we propose the following guideline in the setting of a memory clinic: to perform blood tests in every patient with dementia, but also to perform other tests, such as electroencephalography (EEG) and computed tomography (CT), as clinically indicated.

Measurement of temporal regional cerebral perfusion with single-photon emission tomography predicts rate of decline in language function and survival in early Alzheimer's disease

Abstract. We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer’s disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer’s disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0.01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0.05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer’s disease, with a threshold effect of low rCBF and high risk of mortality.

A simple test of copying ability and sex define survival in patients with early Alzheimer's disease.

BACKGROUNDnWe studied whether heterogeneous profiles of cognitive function are relevant to survival in patients with early Alzheimers disease.nnnMETHODSnCAMCOG subscales of cognitive function were used as predictors of survival, together with gender in 157 consecutively referred patients with early Alzheimers disease. Statistical analysis was performed with Cox proportional hazards analysis and Kaplan-Meier survival curves. Survival rates were compared with those in the general population.nnnRESULTSnEighty patients (51%) died during the follow-up that extended to 5.7 years, with a median survival of 4.4 years after entry. Only the praxis subscore was statistically significant related to survival (P < 0.0001). Its predictive power was based on only two items, including copying ability for a spiral and a three-dimensional house, independent of age, sex, education, overall CAMCOG score, dementia severity and symptom duration. Kaplan-Meier curves for the combined score of these items (0, 1, or 2) showed three groups with significantly different survival rates for both men and women. Comparison of gender specific survival rates with data from the general population showed that excess mortality was statistically significant (P < 0.01) higher in men (51%) than in women (21%) after follow-up extending to 5 years.nnnCONCLUSIONSnA simple test of copying ability defines subgroups of AD patients with large differences in survival rates. This suggests that parietal lobe impairment is an important predictor of mortality in AD. Also, the course of AD may be more benign in women than in men.

SPECT in Early- and Late-Onset Alzheimer's Disease†

We assessed with SPECT the influence of age of onset in Alzheimers disease in patients who were matched for severity of disease with early and late onset of the disease. Twenty-six patients, severity-matched according to scores on Mini-Mental State Examination, were compared to nine controls. Comparison of the temporoparietal cerebellar ratio (TPC) revealed a statistically significantly lower ratio in the early-onset group compared to the late-onset group of patients. These results are in agreement with other imaging, structural, and neurochemical studies, supporting the view of heterogeneity of Alzheimers disease according to age of onset.

THE NEED FOR A SECOND WITNESS IN DIAGNOSING DEMENTIA

observation that eating problems are likely to predict death. The following performance rating scales’ predicted shorter survival time in end-stage dementia: reduced interest in or ability to eat, R = -.39, P < .01; impaired mobility, R = 5 2 , P < .001; and cachexia, R = -.35, P < .02.3 Although these ratings identified patients who were close to death, it is important to note the influence of the palliative care plan on survival time. For instance, enteral feeding in severe dementia may prolong survival a t the cost of more discomfort caused by decubitus ulcers and aspiration pneumonia.’ Also, antibiotic treatment for fever among severely demented palliative care patients may increase survival time.’” Dr. Maletta makes an additional important point: the availability of the Medicare hospice benefit can provide a financial incentive to duplicate services that, in some facilities, may be redundant. No doubt excellent palliative care is provided in some special care units, as well as in some traditional nursing homes, hospitals, and home health programs. However, considerable variability exists in the nature of special care units,” as well as in other health care programs. Problems in providing adequate care in nursing home settings are aggravated by high staff turnover. Nurses aides provide most of the care given to nursing home residents,I2 yet 75% of nurses aides left their jobs within the first year.I3 Anecdotal evidence from hospice staff suggests that these frequent changes in nursing home personnel make it difficult to provide palliative care in a consistent manner. Because their primary mission is the provision of palliative care, hospices remain an important and consistent resource for pain control and relief of symptoms for the end-stage dementia patient as well as support and bereavement counseling for family members. Nevertheless, it would be fiscally irresponsible to ignore the possibility of redundant services. Whether adequate palliative care is being provided without formal hospice support is a decision that may have to be made either on a case by case or facility by facility basis. As capitated systems become more prevalent, it may be less necessary to review for redundancy. On the other hand, patients who need hospice care may have greater difficulty accessing the hospice benefit. Because late referrals often result in hospice care that is “too little, too late,’” this would be an unfortunate outcome indeed.