Brain-specific fatty acid-binding protein is elevated in serum of patients with dementia-related diseases.

BACKGROUND: There is a need for biomarkers in accessible matrices, such as blood, for the diagnosis of neurodegenerative diseases. The aim of this study was to measure the serum levels of brain-type fatty acid-binding protein (FABP) and heart-type FABP in patients with dementia-involving diseases. METHODS: Brain- and heart-type FABP were measured in serum samples from patients with either Alzheimer's disease (AD) (n = 31), Parkinson's disease (PD, n = 43), or other cognitive disorders (OCD, n = 42) and in 52 healthy controls. The localization of brain- and heart-type FABP was determined in brain sections by immunohistochemistry. RESULTS: Brain-type FABP levels were elevated in serum of 29%, 35%, and 24% of the patients with AD, PD, and OCD, respectively, and in 2% of the healthy donors. Heart-type FABP serum levels were not different amongst the patient groups. Brain-type and heart-type FABP expression was observed in reactive astrocytes in brain sections of patients with AD. CONCLUSIONS: In contrast to heart-type FABP, serum levels of brain-type FABP are elevated in a significant proportion of patients with various neurodegenerative diseases and can therefore have importance for defining subgroups of these patients.

Prevalence of primitive reflexes and the relationship with cognitive change in healthy adults: a report from the Maastricht Aging Study.

OBJECTIVES: Primitive reflexes (PR) generally disappear early in life but may reappear later, in which case they are often associated with chronic neurological conditions, such as dementia or Parkinson's disease. Studies have shown that the presence of PRs may be indicative of both the severity and rate of progression of these diseases and may be the result of disinhibition of cortical networks. The association between PRs and cognitive function in usual ageing is unclear. We investigated whether the occurrence, amplitude, and persistence of four nociceptive (glabbelar tap, palmomental, pollicomental, and snout reflexes), three prehensile reflexes (suck, palmar grasp, and rooting), and two other reflexes (mouth open finger-spread and nuchocephalic reflexes) were related to performance in specific cognitive domains in normal ageing individuals. METHODS: Four-hundred and seventy normal aging participants (25-82 years) in the Maastricht Aging Study (MAAS), were included in the study. They were neurologically and cognitively screened at baseline and were retested after 3 (only individuals aged 50 years and older at baseline) and 6 years. RESULTS: The prevalence of most PRs increased with age: 47% of men aged 25-45 years had at least one PR, compared with 73% of men aged 65-85 year (p = 0.002). In women these percentages were 51 and 75, respectively (p=0.008). The prevalence, amplitude, and persistence of PRs were unrelated to cognition at baseline or at the 3- or 6-year follow-up. CONCLUSIONS: The prevalence of particularly nociceptive reflexes rises substantially with increasing age in normal individuals. However, the presence of PRs cannot be considered to be a marker of cognitive decline in normal aging individuals.

Combination of serum markers related to several mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) probably involves several pathobiochemical mechanisms and this may be reflected by changes in different serum components. The present study investigated whether the combined analysis of serum molecules related to different mechanisms improves the discrimination of AD patients from healthy controls. Serum of patients with AD was analyzed for a broad spectrum of marker molecules, including 11 inflammatory proteins, 12 sterol intermediates and phytosterols, 2 brain-specific proteins and 4 constituents involved in homocysteine homeostasis. The serum molecule concentrations were combined in a logistic regression model, using a forward stepwise inclusion mode. The results showed that the combination of interleukin-6 (IL-6) receptor, protein alpha1 fraction, cysteine and cholesterol concentrations improved the discrimination between AD patients and healthy controls compared to the single markers. In conclusion, the results of this study have shown that the complex pathology in AD is reflected in a pattern of altered serum concentrations of several marker molecules related to several pathobiochemical mechanisms.

Primitive reflexes in healthy, adult volunteers and neurological patients: methodological issues.

A study was made to determine whether two experienced clinicians elicited and scored primitive reflexes (PR) differently and whether reliability could be improved by standardization. Three studies were carried out, using a protocol for the examination of 14 PR. In the first study with 31 healthy young subjects, two investigators found virtually no difference in the routine neurological examination. However, the interobserver agreement was very poor, indicating the need for a further improvement of the PR protocol. In the second study, 30 neurological patients were examined with an improved, more explicit and standardized protocol, in which the amplitude and the persistence of the reflex were scored separately. Interobserver agreement improved considerably, and was high for amplitude as well as persistence. In the third study, 36 neurological patients were examined twice by one investigator within 2 weeks. Good to excellent intraobserver agreement was found. No pathognomonic or strictly localizing reflex could be distinguished.

Ruptured abdominal aortic aneurysms presenting as radicular compression syndromes.

Two patients are described: one with an aneurysm of the infrarenal aorta and common iliac artery that ruptured posteriorly into the iliac vein, the other with an aneurysm of the distal abdominal aorta that ruptured posteriorly into the iliopsoas muscle. Both patients had symptoms compatible with a radicular compression syndrome. Ruptured aneurysm of one of the major abdominal arteries should be considered in the differential diagnosis of affections of the lumbosacral neural outflow, because immediate operation can be life-saving.

Successful treatment of tuberculous brain abscess.

A case of tuberculous brain abscess occurred in spite of 4 months' treatment of pulmonary tuberculosis with a triple drug anti-tuberculous regimen. Surgical removal and further chemotherapy were successful.

Primitive reflexes in Alzheimer's disease and vascular dementia.

Data on the prevalence and clinical value of primitive reflexes (PRs) in dementia are controversial, mainly due to a lack of standardization of the methods by which these signs are elicited and scored. A standardized protocol was used to investigate eight PRs in 20 patients with Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 20 control subjects for each group. Both patient groups showed considerably more PRs than the control groups. The prevalence of PRs was related to the severity of dementia. No single reflex or combination of PR pathognomonic for dementia could be distinguished. The PR profile of AD and VD patients were similar.

[Successful treatment of depression in a Parkinson disease patient with bupropion]. / Een depressieve patiënte met de ziekte van Parkinson succesvol behandeld met bupropion.

A 70-year-old female patient with Parkinson's disease was admitted to hospital with a medication-resistant depression. Electroconvulsion therapy was considered indicated, but it was decided to try treatment with bupropion chloride first. This resulted in a quick and complete remission of depressive symptoms, without any negative effects on motor symptoms. Bupropion has a unique mechanism of action: inhibition of the presynaptic reuptake of dopamine in addition to noradrenergic activity. Furthermore, it lacks the negative adverse effects on the extrapiramidal symptoms, that may be a problem if other antidepressants are used in the treatment. Bupropion is useful as an antidepressant in specific patient groups, notably patients with Parkinson's disease.

[Psychiatric disorders in patients of a memory outpatient clinic]. / Psychiatrische stoornissen bij patiënten van een geheugenpolikliniek.

OBJECTIVE: To determine whether psychiatric conditions other than depression are relevant in elder patients with memory disturbances. METHODS: 430 consecutive outpatients (242 males, 188 females; mean age 61.7 years) who visited the Maastricht Memory Clinic were examined, according to a standardised diagnostic procedure, including somatic, neurological, psychiatric and neuropsychological examination. Psychiatric disorders were diagnosed according to DSM-III(-R) criteria. RESULTS: Of 152 patients with dementia, 34 had a secondary depressive syndrome, 19 another secondary psychiatric disorder. Of the 37 patients with a psycho-organic disorder other than dementia, 16 had an organic mood disorder. Of the other 241 patients, 152 had 159 primary psychiatric diagnoses: mood disorders in 100 cases and other psychiatric disorders in 59 cases, especially adjustment disorders, anxiety disorders and personality disorders. Together, only 60% percent of all primary or secondary psychiatric disorders were mood disorders. Various ways in which organic substrate, cognitive problems and psychopathology can be interrelated are discussed. CONCLUSION: Although affective disorders were the most frequent psychiatric disorders, several other psychiatric conditions were related to memory disturbances as well. Psychiatric assessment in patients with memory complaints should not be restricted to the diagnosis of depressive symptoms.

Dementia and Amyotrophic Lateral Sclerosis.

Dementia and Amyotrophic Lateral Sclerosis The case-histories of two patients are presented with Amyo-trofic Lateral Sclerosis and dementia (ALS-D), followed by a discussion of recent literature on this topic. This condition can be considered as the interface between non-Alzheimer frontal lobe dementia and amyotrophic lateral sclerosis. The nosological classification of the ALS-D complex has not been established yet.

Rigorous health screening reduces age effect on memory scanning task.

Eighty subjects participated in a study with five age groups (20, 30, 40, 50, and 60 years). Forty subjects showed evidence of factors related to brain dysfunction (risk factors). Their performance on a Sternberg-type memory scanning task was assessed. Age-related slowing of virtually all aspects of the memory scanning process was observed in the healthy group. However, the effect of the presence of risk factors was larger than that of biological age. The results of the present study make a reasonable case for the view that many age effects reported in the literature can be largely explained by suboptimal brain functioning, i.e., by other factors than aging per se.

Stroop interference: aging effects assessed with the Stroop Color-Word Test.

A large, cross-sectional aging investigation of performance on the Stroop Color-Word Test (SCWT) was carried out. Subjects were 247 volunteers, ages 20-80 in seven age levels. Although all subjects thought themselves to be normal and healthy, a post hoc division could be made on the basis of biological life events (BLE). BLE are mild biological or environmental factors, such as repeated experiences of general anesthesia, that can hamper optimal brain functioning. Apart from the anticipated age effects, performance was poorer in subjects who had experienced one or more BLE: The slowing due to BLE was comparable to the effect of age, especially on the task involving language interference in color-naming. Education had a significant effect on performance: More highly educated subjects performed better than less educated subjects. No sex differences were observed. These findings replicate observations made with other tests in parallel studies. They are also in line with several other studies reporting interactions between the effects of aging and physical fitness. This study questions some of the validity of cognitive aging research, as our data suggest that screening for BLE as age-extrinsic factors in nondiseased subjects can reduce many of the performance deficits usually ascribed to aging per se.

Een zeldzame oorzaak van dementie: de bestralingsencephalopathie.

We describe the clinical history of a 49-year old woman, who demonstrated progressive personality changes more than twenty years after radiation of a pituitary adenoma (prolactinoma), with apathy, loss of initiative, memory deficits, postural instability, dysarthria and faecal incontinence. Neuropsychological assessment showed impulsivity, loss of overview, desinhibition, fluctuating deficits of attention, and memory disturbances. MRI-scanning of the brain revealed a cystic lesion along the right ventricle. The clinical picture and the findings of the other investigations are typical for dementia due to radiation encephalopathy. Such a long period between radiation and cognitive deterioration is rare, although it has been described before.

Stroke and idiopathic Parkinson's disease: does a shortage of dopamine offer protection against stroke?

Data on the relationship between idiopathic Parkinson's disease (IPD) and stroke are conflicting. In this study, we examined the frequency of IPD in stroke patients registered in the Maastricht Stroke Registry. With the use of three different search strategies, we found eight individuals with IPD amongst a total of 1,516 stroke patients. We had expected to find approximately 30 IPD patients (relative risk 0.27; 95% confidence interval 0.11-0.53), based on IPD prevalence figures from a Dutch population-based study. We speculate that dopamine deficiency may protect against ischaemic brain damage, perhaps by reducing the effects of excitotoxicity.

Primitive reflexes in Parkinson's disease.

A standardised protocol for the examination of 15 primitive reflexes in which the amplitude and the persistence were scored separately, was applied to 25 patients with Parkinson's disease and an equal number of healthy matched control subjects. Most reflexes were found considerably more often in the patients than in the control subjects, especially the snout, the glabellar tap, and its variant, the nasopalpebral reflex. Only the mouth open finger spread reflex was present more often in the control subjects. For all reflexes except this last, the scores for amplitude and persistence of the reflexes for the control group never exceeded the scores for the patient group. Reflexes persisted more often in the patients than in the control subjects. Parkinsonism alone can explain a large number of primitive reflexes, irrespective of the severity or duration of the disease. In contrast, the number of reflexes was related more closely to cognitive scales. It is concluded that such reflexes may be helpful in diagnosing Parkinson's disease. In addition, a standardised protocol for eliciting and scoring is essential for the study of these reflexes in parkinsonism and other neuropsychiatric conditions.

The role of serotonin in Parkinsons' Disease: An integrated approach for research of motor, cognitive and affective symptoms with functional intervention studies.

Serotonin seems to play an important role in the regulation of dopaminergic and cholinergic neurotransmitter activities. In patients with Parkinsons' Disease, serotonergic activity is generally reduced, which is considered a compensating mechanism for the reduced dopaminergic activity. At the same time, reduction of serotonin activity may play a role in the expression of cognitive and affective symptoms. Functional intervention with serotonergic agents makes it possible to temporarily enhance or reduce the availability of serotonin in the brain. This will provide the opportunity to study motor, cognitive and affective symptoms in an integrated approach. This type of research has hardly been preformed in patients with Parkinson's Disease.

Diagnosing dementia: a comparison between a monodisciplinary and a multidisciplinary approach.

Discrepancies were examined in diagnostic outcome between a monodisciplinary approach and a multidisciplinary, criteria-based approach in patients referred to a university memory clinic. Of 278 patients not fulfilling dementia criteria, 19 had been previously diagnosed as demented (specificity: 0.93). In 60 of 152 demented patients, dementia had not been diagnosed before (sensitivity: 0.61). Underreporting was frequent for mildly demented patients and for patients with coexisting depressive symptoms. In patients referred by psychiatrists, sensitivity rates for dementia and Alzheimer's disease were low; in patients referred by neurologists, depression often went unreported. Results underscore the need for more frequent use of integrated multidisciplinary services for cognitively disturbed patients.