Saskia Teunisse

Reversible dementia in elderly patients referred to a memory clinic.

Abstract Dementia has a reversible cause in some cases, and these should be diagnosed without over-investigating the many patients with irreversible disease. We prospectively studied the prevalence of reversible dementia in a memory clinic, determined the added value of investigations compared with clinical examination and assessed the outcome of treatment of potentially reversible causes by measuring (1) cognition, (2) disability in daily functioning, (3) behavioural changes and (4) caregiver burden. Two hundred patients aged 65 years and over were examined, using the CAMDEX-N. If they were demented, the probable cause was diagnosed clinically and confirmed or excluded by a standard set of investigations, which were done in all patients. Of the patients, 170 (mean age 79.2 years) were demented; 31 were treated for potentially reversible causes. At follow-up after 6 months, no patients showed complete reversal of dementia. Five patients improved on clinical impression, but only one on clinicial measurement. Thirty patients were cognitively impaired, but not demented; seven were treated. Judged clinically, three patients improved, but on assessment only one did so; she recovered completely. Blood tests often produced diagnostic results that were not expected clinically, but electroencephalography and computed tomography of the brain did not. None of the investigations had an effect on outcome of dementia after treatment. We conclude that in elderly patients referred to a memory clinic, the prevalence of reversible dementia is of the order of 1%, if outcome after treatment is assessed by a standardized measurement. We recommend blood tests in all patients, to detect not only metabolic causes of dementia but also co-morbidity possibly worsening the dementia. Other investigations can be performed on clinical indication. Clinical evaluation remains the mainstay of diagnosis in dementia.

Dementia and subnormal levels of vitamin B12: effects of replacement therapy on dementia.

Routine determination of serum vitamin B12 levels is generally recommended as part of the screening of demented patients, based on the notion that vitamin B12 deficiency is one of the causes of reversible dementia. We studied the effects of vitamin B12 replacement therapy in a prospective longitudinal study at a memory clinic, with special emphasis on assessment of severity of dementia: not only cognitive deterioration, but also disability in the activities of daily life, behavioural problems, and the burden experienced by the caregiver were examined using instruments of proven validity. In a series of 170 consecutive patients with dementia, subnormal serum vitamin B12 levels were found in 26 cases (15%); all but one fulfilled diagnostic criteria for possible Alzheimers disease. Cobalamin supplementation was given to all patients and the effect was evaluated after 6 months. When the size and pattern of individual change scores, and the mean change scores on all instruments were taken into account, functioning after replacement therapy was not improved. When change scores of treated patients were compared with those of patients with Alzheimers disease (n = 69), vitamin B12 replacement did not result in slowing of the progression of dementia. Contrary to widely accepted beliefs, subnormal serum vitamin B12 levels are not a (quantitatively) important cause of reversible dementia.

The Interview for Deterioration in Daily Living Activities in Dementia: Agreement Between Primary and Secondary Caregivers

Inability to perform activities of daily life is inherent to dementia and an essential component of its severity. Examination of this disability is crucial for diagnosis, management of the patient and family, and evaluation of treatment effects. To examine everyday disability in community-dwelling patients with mild dementia, we developed the Interview for Deterioration in Daily living Activities in Dementia (IDDD) at the memory clinic of the Academic Medical Center at Amsterdam. The IDDD is a caregiver-based measure, which consists of 20 concretely worded items, reflecting the initiative to perform and actual performance of self-care and more complex activities. The original version of the IDDD (1988) was an interview measure, but since 1990 a paper-and-pencil version has been used, which has good construct validity and test-retest reliability, as well as good responsiveness to deterioration over 6 months. In the present study, we examined interobserver agreement among 25 caregiver pairs, which consisted of primary and secondary caregivers. Although the reliability of caregiver reports is often questioned, we found substantial to almost perfect agreement at subscale level and acceptable agreement for most of the items. We conclude that the paper-and-pencil version of the IDDD is a suitable instrument for the description and discrimination of disability among patients with mild dementia still living at home. The IDDD may also be a useful method to incorporate in clinical trials and longitudinal studies.

Predicting Survival in Patients with Early Alzheimer’s Disease

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer’s disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer’s disease (105 ‘probable’ and 58 ‘possible’, NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51.5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer’s disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer’s disease.

Diagnosing Alzheimer's disease in elderly, mildly demented patients: the impact of routine single photon emission computed tomography

Based on the observation of bilateral temporoparietal hypoperfusion in Alzheimers disease (AD), single photon emission computed tomography (SPECT) is advocated by some as a powerful diagnostic tool in the evaluation of demented patients. We studied whether routine brain SPECT in elderly, mildly demented outpatients increases the a priori diagnostic sensitivity and specificity of a careful clinical examination.99mTc-HMPAO SPECT imaging was performed in 110 patients for a first evaluation for dementia. A semiquantitative measure of temporoparietal (TP) perfusion was calculated as the ratio of the activity in the temporoparietal cortex to activity in the cerebellum. A diagnosis of probable AD according to the McKhann criteria was made in 68 patients (mean age of 79.3 years) based on the results of a clinical examination, ancillary investigations and a 6-month follow-up. TP perfusion was significantly lower in AD patients than in 18 age-matched, non-demented controls. However, at a specificity of 89%, sensitivity was only 43% for detecting probable AD. The clinicians judged that SPECT had contributed to the final diagnosis in only 8% of the demented patients investigated. Routine brain SPECT in elderly, mildly demented outpatients does not contribute substantially to diagnostic accuracy after a careful clinical examination using current diagnostic criteria. Clinical guidelines have to be developed for the use of SPECT in patients with (suspected) dementia.

Feasibility of cognitive screening of patients with ischaemic stroke using the CAMCOG A hospital-based study

Brief screening tests would be convenient for the measurement of cognitive impairment in stroke patients. In these patients aphasia can interfere with test procedures. To evaluate the feasibility of examining cognitive functions in stroke patients we examined 129 patients with an ischaemic stroke using the CAMCOG, a standardised neuropsychological screening test, after an interval of at least 3 months. Most patients (88%) were able to complete the CAMCOG. Patients with severe aphasia were significantly more likely to have an abnormal CAMCOG score than patients without aphasia [relative risk (RR) 4.0, 95% confidence interval (CI) 2.8–5.8]. The group of patients with moderate aphasia was not at higher risk of having an abnormal CAMCOG score than patients without aphasia (RR 1.4, 95% CI 0.6–2.8). Looking for other factors that might correlate with the scores, logistic regression analysis revealed age as the only significant factor for the prediction of the CAMCOG score (odds ratio 4.0, 95% CI 1.2–13.2). We concluded that the CAMCOG can conveniently be used for screening cognitive functions in patients with cerebral infarcts, even if there is moderate aphasia.

Tetrahydroaminoacridine and lecithin in the treatment of Alzheimer's disease

SummaryIn 12 ambulant patients with a clinical diagnosis of probable Alzheimers disease, a 12-week, double-blind, placebo-controlled study with 100 mg/day tetrahydroaminoacridine (THA) and 10 g/day lecithin is reported. The aim of the study was to find whether treatment would result in an improvement of cognition, of functioning in daily life, decrease of behavioural disturbances, and decrease in burden experienced by the carers. Two of the six THA-treated patients demonstrated an increase on cognitive test scores with a moderate increase in the other outcome measurements. There was, however, no difference between the two groups in any outcome measurement after treatment. In addition, we found a reversible rise of liver transaminases in 4 of 6 patients in the treated group. This pilot study is too small to draw definite conclusions on the use of THA alone or in combination with lecithin. Our results suggest, however, that semi-structured interviews with the carers may be of value in the evaluation of treatment effects in patients with Alzheimers disease.

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.

Symptomatic Treatment of Elderly Patients with Early Alzheimer's Disease at a Memory Clinic

It is widely accepted that excess disability (treatable coexisting physical disorders and psychiatric phenomena) is common in demented patients, and should be looked for carefully and treated properly, as it may result in improvement. This idea, however, does not state what investigations should be performed and what kind of improvement can be expected. Therefore, we studied prospectively in elderly outpatients with early Alzheimers disease the prevalence of excess disability, the results of medication treatment, and the added value of investigations for diagnosis, treatment, and outcome after clinical examination. Outcome was assessed clinically and clinimetrically (using instruments with regard to cognition, disability in daily functioning, behavior, and caregiver burden). Excess disability was present in 66% of patients. Medication treatment was effective with regard to target symptoms, but (partial) reversal of dementia did not occur. Only blood tests produced unexpected results with consequences for treatment and outcome. Positive treatment effects often resulted from clinical examination only. We recommend blood tests in all patients; other investigations can be performed on clinical indication.

Determinants of global clinical change assessment in patients with early Alzheimer's disease

Global clinical impression (GCI) of change is assumed to integrate aspects of both cognitive and noncognitive functioning. We evaluated 140 consecutive patients with probable (n = 90) and possible (n = 50) early Alzheimer’s disease at baseline and after 6 months with measurements of global cognitive function (CAMCOG), behavior, activities of daily living, and burden of the caregiver. After 6 months, both the clinician (GCI-clin) and the caregiver (GCI-care) rated clinical change on a 3-point scale (worse, no change, improved). Data were analyzed with multiple polychotomous logistic regression, adjusted for age and sex. Change in global cognitive function and GCI-care were significantly and independently related to GCI-clin, while changes in activities of daily living and in behavior were significantly and independently associated with GCI-care. The findings suggest a double dissociation. Change in cognition appears to be the major determinant of the clinician’s global impression but not change in behavioral and functional parameters, while global impression of the caregiver is primarily based on change in behavioral and functional measures but not on change in cognition.