CAMDEX, can it be more efficient? Observational study on the contribution of four screening measures to the diagnosis of dementia by a memory clinic team.

OBJECTIVE: To evaluate the efficiency of the CAMDEX by exploring the contribution of its four main screening measures to the diagnosis of dementia at a memory clinic. METHODS: A retrospective descriptive study was conducted on the diagnostic practice in a memory clinic regarding all consecutively referred patients who came for a first assessment. A standardised examination based on the CAMDEX included three cognitive tests (CAMCOG, MMSE, IMCT) and a test for functional competence (BDS). The predictive value of the tests was estimated by uni- and multivariate analysis with the clinical dementia diagnosis (yes/no) as dependent variable, taking into account the patients' age, education, gender and sensory ability. RESULTS: Of the 180 patients consecutively referred, 150 completed the assessments and entered the study. Multivariate analysis revealed that the CAMCOG-score contributed most to the clinical diagnosis and was consistent with 84% of the clinical diagnoses using the conventional cutoff 79/80. The CAMCOG-score correlated best with the clinical diagnosis, however, at a cutoff score of 81/82. Forty-one patients (27%) scored closely around (+/-5 points) the CAMCOG cutoff of 79/80. In this group 19 of the total of 23 deviations from the CAMCOG cutoff (83%) occurred. The patients' age, education, gender and visual ability explained some cases where the team's diagnosis deviated from the conventional cutoff score. CONCLUSION: Among four screening measures, after control, the CAMCOG was the only significant predictor for the clinical diagnosis of dementia. To gain efficiency, the screening measures of the CAMDEX protocol may be restricted to the CAMCOG. The interpretation of CAMCOG-scores around the cut-off is problematic. This indicates the need for reference values.

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

BACKGROUND: Dementia screening instruments, such as the Cambridge Cognitive Examination (CAMCOG), measure a variety of cognitive functions. However, memory impairment generally is the first sign of Alzheimer's 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. METHODS: Normal 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. RESULTS: Logistic 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. CONCLUSION: For the early detection of AD it is best to use the memory and non-memory sections separately instead of the total CAMCOG score.

Long-term outcome of cognition and functional health after cerebral venous sinus thrombosis.

The authors examined cognition and functional health of 57 patients with sinus thrombosis 1 year or more after enrollment in a randomized trial of anticoagulant treatment or placebo. Eight patients died and two declined participation. Of the remaining 47 patients, 16 (35%) had cognitive impairments, 3 (6%) were dependent, 19 (40%) had symptoms that led to restrictions in lifestyle, and 19 (40%) could not resume their previous level of economic activity. Outcome after sinus thrombosis may be less favorable than reported previously, and was not significantly influenced by treatment.

Outcome measures for the study of activities of daily living in vascular dementia.

Decline in functional abilities is a major component of the dementia syndrome. The definition of dementia in the International Classification of Diseases (10th rev.) requires a cognitive impairment sufficient to impair personal activities of daily living (ADL). The Diagnostic and Statistical Manual of Mental Disorders (4th ed.) also requires cognitive deficits sufficiently severe to cause impairment in occupational or social functioning and must represent a decline from a higher level of functioning. However, the term disability is more appropriate than impairment to describe a loss in activities, as opposed to a loss of elementary functions, and is consistent with World Health Organization definitions of impairment, disability, and handicap. There is no doubt that ADL outcomes are required in therapeutic drug studies on vascular dementia, and there is a good rationale and some evidence for the use of ADL scales developed for therapeutic research in Alzheimer disease, favoring scales devoid of items sensitive to physical disabilities. Similarly, ADL-related clinical milestones could be used for longer-term studies aiming predominantly at slowing progression of disease in both early and later stages of dementia. Slower decline in ADL and delay in reaching ADL-related clinical milestones should be considered as valid outcomes by regulatory bodies in the process of dementia drug approval.

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

BACKGROUND: We studied whether heterogeneous profiles of cognitive function are relevant to survival in patients with early Alzheimer's disease. METHODS: CAMCOG subscales of cognitive function were used as predictors of survival, together with gender in 157 consecutively referred patients with early Alzheimer's 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. RESULTS: Eighty 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. CONCLUSIONS: A 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.

Slowing on quantitative spectral EEG is a marker for rate of subsequent cognitive and functional decline in early Alzheimer disease.

The relation between quantitative spectral electroencephalogram (qEEG) parameters and subsequent rate of cognitive, functional, and behavioral decline in 82 consecutive patients with early probable Alzheimer disease (NINCDS-ADRDA criteria) was examined in a prospective study. The qEEG was performed at initial examination and global cognitive function, activities of daily living, and behavior were assessed at initial evaluation and after a period of 6 months. Using multiple linear regression analysis, higher frontocentral and parieto-occipital theta values, lower parieto-occipital beta values, and lower peak frequency were significantly associated with more decline in global cognitive function over the follow-up period. In addition, lower parieto-occipital beta values were significantly related to more decline in activities of daily living. These associations were independent of demographic (age, sex, and education) and disease characteristics [initial Cambridge Examination for Mental Disorders of the Elderly Cognitive test (CAMCOG) or Mini-Mental State Examination scores, estimated duration of symptoms, estimated prior rate of decline, and dementia severity]. In a separate multiple logistic regression analysis, prediction of rapidly progressive decline, defined as 8 or more points decline in CAMCOG scores (n = 21), could be made with parieto-occipital and frontocentral beta values. The results suggest that slowing on qEEG is a marker for subsequent rate of cognitive and functional decline in mildly demented AD patients, independent of demographic or disease characteristics.

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.

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.

[Several patients with memory disorders]. / Enkele patiënten met geheugenstoornissen.

In three patients, referred to a memory clinic because of memory impairment, three different types of memory dysfunction were observed: a deficit in encoding of new episodic memories, a relatively pure loss of semantic memory and an impairment in retrieval of stored information. These patients were diagnosed as suffering from Alzheimer's disease, semantic dementia and frontotemporal dementia respectively. The diagnosis was essential in determining the individual management strategy.

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 Alzheimer's 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.

Reversible dementia in elderly patients referred to a memory clinic.

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 clinical 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.

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.

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 Alzheimer's 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 Alzheimer's 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.

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.

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 Alzheimer's 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.

[CAMDEX-N: the Dutch version of the Cambridge Examination for Mental Disorders of the Elderly with automatic data processing]. / CAMDEX-N: de Nederlandse versie van de Cambridge Examination for Mental Disorders of the Elderly met geautomatiseerde dataverwerking.

In the study of dementia four distinct categories of instruments can be distinguished: instruments to examine cognitive dysfunction, to measure the severity of dementia, to assess disturbances in daily behaviour, and instruments to make a differential diagnosis of dementia. The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), published in 1988, incorporates these four categories in a single comprehensive interview schedule. Items related to the diagnosis of clouded/delirious state, depression and other psychiatric symptoms are also included. The Dutch version (CAMDEX-N) and accompanying software for data analysis and for scientific research were developed. Items were added to the section on physical and neurological examination, and to the section on ancillary investigations. The software can be adapted to future developments in dementia research.

[Measurement of activities of daily living in patients with dementia living at home: development of a questionnaire]. / Meten van het dagelijks functioneren van thuiswonende dementiepatiënten: ontwikkeling van een vragenlijst.

In clinical practice and for scientific research a method is needed for the assessment of changes in functioning in daily life of dementia patients living at home. As existing methods have their limitations, a questionnaire was developed (the Interview for Deterioration in Daily life in Dementia: IDDD), to be answered by caregivers. The questionnaire concerns self-care and complex activities, that are usually performed by men as well as women. Attention is paid to the difference between lack of initiative and impaired performance itself. Caregivers are interviewed in a structured interview. A study among 30 caregivers of dementia patients living at home, showed the relevance and usefulness of the questions. The questionnaire shows high internal consistency, which may be the result of our structured interview technique.

Assessing the severity of dementia. Patient and caregiver.

In dementia there is cognitive impairment, disability in daily life, and sometimes behavioral disturbance. These changes are a burden for the caregivers of patients with dementia. Few studies are available that examine all these aspects and their interrelationships in a single patient group. In our study we selected detailed methods for assessment of all these aspects. Interrelationships were studied in 30 mild to moderately impaired patients with dementia and their caregivers. Although the relations of cognitive deterioration to disability in daily life and of burden experienced by the caregiver to patient's condition were stronger than often reported, it was impossible to deduce the overall severity of dementia from one single aspect. Thus, for effective management of patients and caregivers, for evaluation of individual treatment or of clinical trials, attention should be paid to all the different aspects of patients' condition and caregivers' burden. Outcome measurements will then be more valid.