Presentation and course of AIDS dementia complex: 10 years of follow-up in Amsterdam, The Netherlands.

OBJECTIVE: To assess the clinical presentation and course of the AIDS dementia complex (ADC). DESIGN: Retrospective study of a consecutive series of symptomatic HIV-1-infected patients [Centers for Disease Control and Prevention (CDC) stages IVA, B, C and D] evaluated for neurological symptoms between 1982 and 1992. SETTING: An academic referral centre for AIDS. PATIENTS: A total of 536 symptomatic HIV-1-infected patients evaluated for neurological symptoms between 1982 and 1992. INTERVENTIONS: Zidovudine treatment, which was introduced in The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (CDC stages IVA, B, C and D). MAIN OUTCOME MEASURES: Diagnosis of ADC and CD4 cell count, clinical features, neuropsychological abnormalities, computed tomography (CT) and magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid (CSF) findings and course in patients with ADC. RESULTS: ADC was diagnosed in 40 out of 536 (7.5%) immunosuppressed, neurologically symptomatic HIV-1-infected patients in CDC stage IV, and was the AIDS-defining illness in six. The mean CD4 cell count of the 40 patients with ADC was 109 x 10(6)/l. Neuropsychological abnormalities in 15 out of 17 patients tested were in accordance with subcortical dementia. On CT scan of the brain, 70% showed no or only mild cortical atrophy. MRI was more sensitive than CT scan for detecting white matter abnormalities (73 versus 35%; P = 0.02). CSF examination showed mononuclear pleocytosis in 25%, protein level increase in 55%, and HIV-1 p24 core protein in 38% (13 out of 34). The mean survival was 6.7 months in the 40 ADC patients, but 4 months in 20 patients who had never used zidovudine, compared with 14.8 months in 10 patients who started zidovudine after they were classified as having ADC (P < 0.001). Three of these 10 patients improved remarkably, and two slightly, after starting zidovudine. ADC developed after discontinuation of zidovudine in nine patients. Only one patient developed ADC while receiving 600 mg zidovudine. CONCLUSIONS: MRI is more sensitive than CT for detecting white matter abnormalities. To date, there is no specific or sensitive CSF marker for ADC. Zidovudine may improve symptoms and prolong survival in patients with ADC, which rarely developed with continued zidovudine use in our study.

Decline of HIV antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine.

Six HIV-antigenaemic patients with AIDS or AIDS-related complex were studied to assess the effect of treatment with low-dose zidovudine (250 mg) in 6-hourly doses on HIV antigen (HIV-Ag) levels in cerebrospinal fluid (CSF). HIV-Ag was detected in CSF of three patients before treatment. These patients became CSF HIV-Ag-negative within 8 weeks of treatment. One initially CSF HIV-Ag-negative patient became strongly CSF HIV-Ag-positive during interruption of zidovudine treatment; CSF HIV-Ag disappeared again after treatment was restarted. None of our patients showed a significant neurological improvement during the study. These results show that low-dose zidovudine can suppress viral expression in CSF. Whether suppression of viral replication can prevent future HIV-related neurological disease remains to be investigated.

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.

SPECT in early- and late-onset Alzheimer's disease.

We assessed with SPECT the influence of age of onset in Alzheimer's 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 Alzheimer's disease according to age of onset.

Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on MRI. MR images were assessed by a neurologist and a neuroradiologist blinded to the clinical data. Thirty-six patients had one or more lacunar infarcts on CT or MRI (in the thalamus in 5, in the caudate nucleus in 3 and in the internal capsule or corona radiata in the remaining patients). Twelve patients had multiple infarcts. Severe lesions of the white matter were found in 13 patients, mild to moderate lesions in 20 patients. Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were significantly lower in group with severe lesions, whilst there was a trend in the same direction for the Cognitive part of the Cambridge Examination of Mental Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and the delayed visual reproduction of the Wechsler Memory Scale. These findings suggest that diffuse lesions of the white matter are an independent factor in the pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts, but a truly independent analysis is difficult because the most severe involvement of the white matter tended to be associated with the largest number of lacunar infarcts.

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.

Salivary cortisol patterns and cognitive speed in major depression: a comparison with allergic rhinitis and healthy control subjects.

Few studies have investigated the relationship between cortisol and cognitive functions other than memory in depression. This study investigated daily salivary cortisol patterns (basal cortisol levels at 08:00, 16:00, and 21:00 h and flatness of the diurnal curve) in relation to cognitive speed and memory. Twenty-seven unmedicated outpatients with major depressive disorder (MDD) were compared with 36 healthy controls and with 20 allergic rhinitis patients, to determine whether effects should be ascribed to MDD or to more general disease-related processes. MDD patients were characterised by a flatter diurnal cortisol curve and by reduced cognitive speed. Flatter cortisol curves were associated with cognitive slowness. However, this relationship is unlikely to be causal; after control for depressive symptoms and group membership, flatness of the diurnal cortisol curve was no longer a significant predictor of cognitive slowness. Thus, MDD and related depressive symptoms appeared to be independently associated with altered cortisol secretory patterns and with decrements in cognitive speed.

Mental changes in subcortical arteriosclerotic encephalopathy.

We describe six patients with chronic hypertension, atherosclerotic vascular disease and periventricular leukoencephalopathy (PVL) on CT. PVL was combined with cortical infarcts in one and with lacunar infarcts in five patients. On neuropsychological examination all patients showed the characteristic features of a subcortical type of mental deterioration. Clinico-radiologic correlation suggests a direct association of PVL and subcortical dementia, and it is argued that prominent cortical features in the dementia of patients with vascular disease and PVL suggest the concomitant presence of Alzheimer's disease.

Mental changes in patients with AIDS.

Mental changes are common in patients with acquired immunodeficiency syndrome (AIDS). Neuropsychological data of 32 patients with AIDS and cognitive symptoms were reviewed. All patients were neurologically examined and ancillary investigations were performed. According to the neuropsychological data three groups could be distinguished: I) 4 patients with dementia and cortical deficits; II) 16 patients with subcortical dementia; III) 12 patients with subcortical cognitive deficits without global intellectual deterioration. AIDS Dementia Complex (ADC) was diagnosed in 12 patients and occurred in all three groups. The most frequent form of dementia in patients with AIDS is of a subcortical type. Impaired memory or reduced psychomotor speed, or both, are common in patients without global intellectual deterioration. ADC seems an unlikely diagnosis in patients with cortical dementia. Neuropsychological examination is important for diagnosing ADC but the diagnosis cannot be made without regarding the neurological findings and ancillary investigations.

Determination of cerebral blood flow by SPECT: a valuable tool in the investigation of dementia?

Positron emission tomography (PET) studies have demonstrated distinctive abnormalities in Alzheimer's disease (AD), multi-infarct-dementia (MID) and Pick's disease. Since PET is a complicated and expensive technique, its clinical application will be limited in the near future. An important finding in these PET studies is persistent coupling of brain metabolism and regional cerebral blood flow (rCBF). Therefore it should be possible to demonstrate bilateral temporoparietal hypometabolism as seen in patients with clinically diagnosed AD indirectly by measuring cerebral blood flow by Single Photon Emission Computer Tomography (SPECT). We report our first experiences with SPECT in the differential diagnosis of dementia with four case histories. We demonstrated temporoparietal hypoperfusion in AD and frontal hypoperfusion in Pick's disease as shown previously by PET. We could not demonstrate a typical SPECT in MID. The main purpose of SPECT in MID could be exclusion of coexisting AD. Based on current knowledge the possibilities and the limitation of this new technique are discussed. It is concluded that rCBF-SPECT may be of value in the diagnosis of AD and Pick's disease. Before this method can be used in daily clinical routine, its diagnostic value should be established according to principles of clinical decision making.

SPECT in the diagnosis of Alzheimer's disease and multi-infarct-dementia.

SPECT with Tc-99m HM-PAO as a radiopharmaceutical was performed in 17 patients meeting research criteria for Alzheimer's disease (AD), in 10 patients with a clinical diagnosis of multi-infarct-dementia (MID) and in 12 healthy volunteers. Regional tracer uptake was measured in frontal, parietal, and temporoparietal regions. A statistically significant decrease of tracer uptake in the temporoparietal region was found in AD-patients compared with controls. AD-patients showed less activity in this region than MID-patients, but this difference did not reach statistical significance. In both AD- and MID-patients decrease of tracer uptake was not correlated with dementia severity. We conclude that SPECT brain imaging is not yet ready for routine use in the distinction between AD and MID.

[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.

[Consensus on the concepts of cortical, subcortical and frontal dementia. Research by national and international dementia experts]. / Consensus over de begrippen corticale, subcorticale en frontale dementie. Een onderzoek onder nationale en internationale dementie-experts.

The level of agreement concerning the concepts cortical, subcortical and frontal dementia. The level of agreement between experts in the field of dementia concerning cortical, subcortical and frontal dementia was established. Nowadays these syndromes are implemented in clinical practice; the discussion about the validity and reliability of these concepts however has diminished. Forty-one national and international dementia experts of four disciplines completed a questionnaire, based on the cognitive section of the CAMDEXR. For each syndrome they marked whether the cognitive function mentioned was impaired or unimpaired in cortical, subcortical and frontal dementia. The level of agreement between experts was determined by use of a derivative of the kappa-coefficient. Cortical dementia was characterised by high levels of agreement between the experts. With an observed level of agreement of 0.76, experts reached the highest consensus about this syndrome. Less agreement was observed in the judgements of subcortical and frontal dementia, with observed levels of agreement of 0.64 and 0.67 respectively. No differences were found in the assessments of national and international experts, as well as between the participating disciplines. Apparently, the application of these syndromes in clinical practice is difficult. Because of this confusion the practical meaning is limited, and one may wonder wether these concepts must still be used in clinical practice.

[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.

Declining incidence of AIDS dementia complex after introduction of zidovudine treatment.

OBJECTIVE: To assess the incidence of the AIDS dementia complex and the presence of HIV I p24 antigen in cerebrospinal fluid in relation to zidovudine treatment. DESIGN: Retrospective study of a consecutive series of patients with AIDS from 1982 to 1988. SETTING: An academic centre for AIDS. PATIENTS: 196 Patients with AIDS and neurological symptoms examined from 1982 to 1988. INTERVENTIONS: Zidovudine treatment, which was introduced to The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (Centers for Disease Control groups IVA, B, C, and D). MAIN OUTCOME MEASURES: Diagnosis of AIDS dementia complex and presence of HIV I p24 antigen in cerebrospinal fluid. RESULTS: The AIDS dementia complex was diagnosed in 40 of the 196 (20%) patients with AIDS. Thirty eight of 107 patients with AIDS (36%) not taking zidovudine developed the AIDS dementia complex compared with two of the 89 (2%) taking the drug (p less than 0.00001). The incidence of the AIDS dementia complex increased to 53% in the first half of 1987, after the introduction of zidovudine in May 1987, decreasing to 10% in the second half of 1987 and to 3% in 1988. Dementia was diagnosed before definition of the AIDS dementia complex (1986) according to DSM-III criteria and there was good agreement between diagnosis before and after 1986. Sixteen of 61 samples of cerebrospinal fluid (26%) from patients with AIDS (10 with the AIDS dementia complex) not taking zidovudine were positive for HIV I p24 antigen, whereas none of 37 cerebrospinal fluid samples from patients with AIDS (two with the AIDS dementia complex) taking zidovudine were positive. CONCLUSIONS: The incidence of AIDS dementia complex in patients with AIDS declined after the introduction of systematic treatment with zidovudine; the AIDS dementia complex might be prevented by inhibiting viral replication in the central nervous system.

[An outpatient clinic for memory disorders; initial experiences]. / Een polikliniek voor geheugenstoornissen; eerste ervaringen.

The department of neurology of the Academisch Medisch Centrum started an outpatient memory clinic in 1987 for patients aged 65 and older. Its specific aims are: assessment of elderly patients with memory problems, treatment where appropriate, and advice; clinical research; teaching and training. The clinic has run full-time since 1990. The approach is multidisciplinary. We describe our findings in the first 75 patients who were referred by their general practitioners because of forgetfulness or possible dementia: 72 of them had a complete investigation; 30 patients were not demented; three could be reassured because their performance was within normal limits. Four patients were depressed and they improved on therapy. Forty-two patients were demented. All had a CT scan and comprehensive blood tests but a curable cause for the dementia syndrome was never identified. This result was expected on account of the probably low frequency of 'reversible' causes and patient selection. Secondary prevention was important when a vascular component contributed to the pathogenesis of the mental deterioration (n = 6). Even when no curable condition was found, clarity about diagnosis and prognosis was important not only to the relatives but also to the general practitioner in planning the future management of the patient. Fifty-five of the 72 patients were older than 65 years which means that we do see the patients we are particularly interested in. The clinic offers facilities for clinical research. In the project 'Diagnostiek bij dementiesyndroom' (Diagnostics in dementia syndrome) we investigate the utility of ancillary investigations in relation to the outcome in demented patients.