Practical application of brief cognitive tests.

INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

Plasma progranulin levels in cortical dementia phenotypes with asymmetric perisylvian atrophy.

BACKGROUND AND PURPOSE: Decreased plasma progranulin levels are a very specific marker for the diagnosis of frontotemporal lobar degeneration (FTLD) caused by mutations in the progranulin gene (GRN). A frequent neuroimaging pattern in this type of dementia is asymmetric cortical atrophy. The aim of this study was to screen for GRN-linked FTLD in cases with different cortical dementia phenotypes and asymmetric perisylvian atrophy. METHODS: Progranulin plasma levels were analyzed in a variety of FTLD phenotypes (n = 71), dementia of the Alzheimer type (DAT) (n = 22) and probable Lewy body dementia (n = 8), both latter groups presented with asymmetric perisylvian atrophy. A group of elderly controls (n = 29) and DAT cases with symmetric atrophy (n = 33) were also analyzed. The GRN gene was sequenced in cases with lower plasma levels. RESULTS: Four cases with clinical FTLD phenotypes and plasma levels below 70 ng/ml were found to carry different GRN mutations: M1?, C139R, a point mutation in the splice donor site of intron 3 (A89VfsX41), and a deletion in exon 9 (A303AfsX57), this latter one being a new mutation. Thirteen cases with levels between 72 and 85 ng/ml did not show pathogenic changes in the GRN gene. None of the cases with asymmetric atrophy and clinical phenotypes other than FTLD had GRN mutations. CONCLUSIONS: Asymmetric perisylvian atrophy is not likely to predict progranulin-linked FTLD unless it is associated with a consistent FTLD clinical phenotype.

Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.

BACKGROUND AND PURPOSE: To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. METHODS: Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. RESULTS: The interrater agreement for the baseline investigation was fair to good for all scales (kappa values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (kappa, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation (z value, -2.9676; P=0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P< or =0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W, 0.37, 0.48, and 0.57; P<0.001). CONCLUSIONS: Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

Temporal pattern of cognitive decline and incontinence is different in Alzheimer's disease and diffuse Lewy body disease.

Incontinence is a hallmark of dementia, but little is known about its inception in different types of dementing disease. We recorded the dates of onset of dementia and of urinary incontinence in 73 demented patients followed for 5.6 +/- 2.5 years. The pathologic diagnosis was Alzheimer's disease (AD) in 29 cases, diffuse Lewy body disease (DLBD) in 11 cases, AD with Lewy bodies (AD+LB) in 13 cases, and AD with vascular lesions (AD+VL) in 20 cases. The onset of urinary incontinence was significantly earlier in DLBD cases (3.2 +/- 1.4 years after dementia onset) than in AD (5.9 +/- 2.5), AD+LB (5.8 +/- 2.4), and AD+VL (6.5 +/- 2.3) (p < 0.01). At the onset of bladder incontinence, the mean score in the Extended Dementia Scale was significantly higher (i.e., cognition was better) in DLBD cases (109.3 +/- 70.8) than in AD (21.3 +/- 40.4), AD+LB (45.6 +/- 45.1), and AD+VL (39.2 +/- 54.9) cases (p < 0.01). Urinary incontinence is associated with severe cognitive decline in pure AD but usually precedes severe mental failure in DLBD cases. This temporal pattern of cognitive decline and incontinence could be useful in differentiating these two dementing illnesses.

Subcortical vascular dementia as a specific target for clinical trials.

Vascular cognitive impairment is considered the second most common form of mental deterioration in the elderly after degenerative dementias. Therapeutic approaches to vascular dementia mainly rely on the identification and treatment of risk factors. A number of drugs have also been tested with the aim of improving or slowing cognitive decline in patients affected by various forms of cerebrovascular disease. Most of these trials have yielded unsatisfactory results. We hypothesize that some of these failures depend on the inclusion of patients with pathophysiologically heterogeneous types of vascular cognitive decline. In this paper, we review some of the most important trials that tested drugs with a preventive or therapeutic aim in vascular dementia patients. Preliminary results suggest that some beneficial effects can be detected only when the trial population is homogeneous on a clinical and pathogenic basis. In particular, subcortical vascular dementia, a form with a rather univocal clinical, radiological, and pathological picture, seems a particularly apt choice as a target for future clinical studies. At present, only one therapeutic trial is being conducted in patients affected by this specific form of vascular dementia.

Anticholinergic therapy and dementia in patients with Parkinson's disease.

In a cross-sectional study performed in 1980 on 70 consecutive Parkinson's disease (PD) outpatients, we investigated the factors associated with dementia, especially anticholinergic drugs. All cases fulfilled three major clinical criteria of PD, and underwent extensive clinical and laboratory examinations, including brain CT and neuropsychological assessment. Cases with mental deterioration at the onset of the illness or confusional status were excluded. In 15 patients the diagnosis of dementia was made according to DSM-III criteria; 15 other non-demented patients scoring 4 on the Reisberg's Global Deterioration Scale were labelled as "mentally deteriorated", and the remaining 40 cases were considered cognitively normal. In a logistic multiple regression analysis only age, female sex and time of anticholinergic intake were significantly associated with dementia. We conclude that anticholinergic drugs must be avoided in PD patients with some cognitive decline.

Relationship of angiotensin converting enzyme genotype with serum triglyceride concentration in stroke patients.

The Objective of this research was to study the relationship of angiotensin converting enzyme (ACE) genotype with serum triglycerides concentration in stroke patients. The insertion/deletion (I/D) ACE polymorphism was identified by using polymerase chain reaction in 122 prospectively studied ischemic stroke patients (age 45-91 years). Serum triglycerides concentration was determined at admission and 3 months after the stroke, and compared between the ACE genotype groups (37 D/D, 68 D/I, 17 I/I). All clinical characteristics were similar in the three groups. Patients with D/D genotype had mean serum triglycerides concentration significantly higher in acute (179.0+/-111.8 mg/dl) and chronic phase (176.4+/-121.6 mg/dl) than those with I/I genotype (acute phase: 108.7+/-36.1 mg/dl, P=0.019; chronic phase: 116.0+/-44.3 mg/dl, P=0.021). The results showed that serum triglycerides concentration is elevated in stroke patients with the DD ACE genotype and it may be related to the risk of cerebrovascular disease associated with this polymorphism.

Neurotransmitter changes in cerebrospinal fluid in the Spanish toxic oil syndrome: human clinical findings and experimental results in mice.

Patients with Spanish Toxic Oil Syndrome (TOS) complaining of neuromuscular symptoms had increased levels of homovanillic acid and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid. Severity of pain and muscle cramps correlated with the magnitude of increment in levels of monoamine metabolites. Mice treated with oleyl anilide, a putative toxic compound found in some stocks of the toxic rapeseed oil, did not present clinical or anatomical findings compatible with TOS. However, biochemical studies in these mice revealed a depletion of serotonin and an elevation of 5-HIAA levels. Our findings suggest that the unidentified toxic agent of the TOS and oleyl anilide induce pharmacological changes in monoamine neurons of the brain.

Truncal ataxia in chronic anticonvulsant treatment. Association with drug-induced folate deficiency.

The association of truncal ataxia with a number of different factors has been studied in a group of 95 epileptic outpatients on chronic anticonvulsant treatment. The 28 patients showing truncal ataxia had been epileptic for a longer period of time, received a significantly larger number of drugs, and had higher serum levels of phenobarbital than the non-ataxic group. Serum folate levels were significantly lower in the ataxic group. A role is postulated for anticonvulsant-induced folate deficiency in the appearance of truncal ataxia presenting after prolonged anti-convulsant therapy, either by increasing the serum levels of the anticonvulsants or through other, unknown mechanisms. The presence of tonic-clonic seizures, presumably associated with brain anoxia, was not associated with the appearance of truncal ataxia.

Vascular dementia. A clinicopathological study.

We have reviewed the clinical and pathological records of 40 aged patients who showed only vascular lesions on histological examination. They were followed up for 3.5 +/- 6.3 years before death, and in 28 cases the diagnosis of dementia was done during life. Demographic data, vascular and systemic illnesses, psychiatric neurological and neuropsychological disturbances, and pathological findings were compared between demented and non-demented patients. The number of strokes, several neurological and almost all neuropsychological disturbances, the volume of macroscopic cerebral infarct, especially in frontal, occipital and basal regions, the lacunar state and the white matter lesions, were significantly greater in demented patients. However most of them had less than 100 ml3 of brain infarct. The relative influence of each type of cerebral vascular lesion upon the dementia syndrome was determined by means of multivariate analysis. The volume of macroscopic cerebral infarct, the white matter lesion and the lacunar state showed quite similar contributions to mental deterioration.

Serum levels of vitamin A in Parkinson's disease.

To elucidate a possible role of vitamin A in the pathogenesis of Parkinson's disease (PD) we compared serum levels of retinol (vitamin A), measured by HPLC, and the vitamin A/retinol binding protein (RBP) ratio of 42 PD patients (22 males and 20 females, mean age 67.3 +/- 1.34 years) and their respective spouses as control group (20 males and 22 females, mean age 66.2 +/- 1.42). The serum levels of vitamin A did not differ significantly between the 2 groups (0.59 +/- 0.03 microgram/dl for PD patients and 0.57 +/- 0.03 microgram/dl for controls), nor did the vitamin A/RBP ratio (0.87 +/- 0.04 and 0.82 +/- 0.03, respectively). There was no influence of antiparkinsonian therapy on vitamin A or vitamin A/RBP ratio. Serum levels of vitamin A, and vitamin A/RBP ratio did not correlate with age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the Hoehn and Yahr staging in the PD group. These results suggest that serum concentrations of vitamin A, do not play a role in the pathogenesis of PD.

[A comparison between 2 abbreviated Spanish versions of mental status assessment in the diagnosis of dementia. Study data on elderly community residents]. / Comparación entre dos versiones españolas abreviadas de evaluación del estado mental en el diagnóstico de demencia. Datos de un estudio en ancianos residentes en la comunidad.

BACKGROUND: There are several Spanish versions and adaptations of the Mini-Mental State Examination (MMSE), the most used abbreviated test for screening of the cognitive decline in clinical and epidemiological setting. Among them, the Mini-Examen Cognoscitivo (MEC) is highlighted. The aim of this study was to compare the diagnostic usefulness between the Spanish translation of the MMSE (the MMSE1 which incorporates the proof of serial "sevens" and the MMSE2 which includes spelling "world" backward) and the MEC for the diagnosis of dementia. PATIENTS AND METHODS: A sample of elderly persons (65 years or over), included in a population-based study of dementia prevalence. The diagnosis of dementia was assessed through exhaustive neuropsychological evaluation. The diagnosis of dementia (according to the standardized DSM-III-R criteria) was carried out by expert neurologists, who were independent and blind to the scores obtained in the MMSE and MEC. RESULTS: 79 subjects underwent both tools and neuropsychological assessment. The MMSE1 obtained the highest accuracy (92%), followed by the MEC (90%) and the MMSE2 (83%). The analysis of the areas under receiver operating characteristic curves did not show significant statistical differences between the MMSE1 and MEC (p = 0.38), but significant differences were observed between those and the MMSE2 (p = 0.01). CONCLUSIONS: The diagnostic usefulness of Spanish translation of the MMSE is similar to the MEC. The proof of spelling "world" backward obtained poorer results than serial "sevens". The Spanish versions of the MMSE should be improved to be adapted to our cultural characteristics.

[Dementia with Lewy bodies. Pure and mixed forms]. / Demencia con cuerpos de Lewy. Formas puras y mixtas.

INTRODUCTION AND METHOD: Dementia with Lewy bodies is a generative brain disease of unknown origin, characterised clinically by progressive mental deterioration, with striking fluctuations and transitory episodes of confusion, hallucinations and psychotic symptoms (hallucinations and paranoid deliria), extrapyramidal signs and hypersensitivity to neuroleptic drugs. The main pathological finding was the abundance of Lewy bodies in the neurons of the cortex, brain stem and other subcortical nuclei. In many cases, however, varying amounts of Alzheimer like degenerative lesions are associated. CONCLUSION: This study analyses the anatomopathological, clinical, diagnostic and therapeutic aspects of this disease.

[Neurological complications in a series of 205 orthotopic heart transplant patients]. / Complicaciones neurológicas en una serie de 205 trasplantes cardíacos ortotópicos.

INTRODUCTION: A heart transplant is the only effective therapeutic option open to many patients with severe heart failure and performing such an intervention is not free of complications. Little is known about the risk factors for neurological complications after a heart transplant. AIMS: The aim of this study was to identify the risk factors for neurological complications following a heart transplant and, more especially, those associated with epileptic seizures, encephalopathy, cerebrovascular accidents (CVA) and headaches. PATIENTS AND METHODS: We conducted a retrospective review of the records of 205 orthotopic heart transplant patients and collected clinical, haemodynamic and laboratory data before, during and after the intervention, using a standardised protocol. RESULTS: 95 patients (48%) presented neurological complications. Their frequencies were as follows: encephalopathy (16.6%), epileptic seizures (13.6%), neuromuscular disorders (10.6%), headaches (10.6%), CVA (10.1%), psychiatric disorders (2.2%) and infection of the central nervous system (2.2%). The risk factors for encephalopathy were post-transplant renal failure (RR: 4.6; CI 95%: 1.4-15), post-transplant hepatic failure (RR: 5.6; CI 95%: 1.5-22) and pre-transplant haemodynamic instability (RR: 4.3; CI 95%: 1.3-14); for epileptic seizures they were a cardiac index of < or = 2 L/min/m2 (RR: 23.8; CI 95%: 2-247) and extracorporeal circulation time > or = 115 min (RR: 11.3; CI 95%: 1-79); and for CVA the risk factor was post-transplant hepatic failure (RR: 12.9; CI 95%: 2.5-66). CONCLUSIONS: Neurological complications often occur after a transplant and are transient. Perioperative haemodynamic instability giving rise to cerebral ischemia and the metabolic disorders secondary to multiple organ failure are determining factors of encephalopathy, epileptic seizures and CVA.

[Findings using magnetic resonance in a patient with non-traumatic anosmia]. / Hallazgos mediante resonancia magnética en un paciente con anosmia no postraumática.

INTRODUCTION: The presence of alterations in the neuroimaging in patients with anosmia without traumatic antecedents is not frequent. CASE REPORT: Male aged 38 who came to surgery after having suffered, 6 months earlier, for 1 week, a picture of intense, oppressive holocranial headache, accompanied by fever. Associated with this, an acute complete anosmia also began and persisted up to the moment the patient came for consultation. It was not associated with any infection of the respiratory tract, there was no history of cranial trauma, no ingestion of medicines nor toxins, nor had he been exposed to toxic products. The exploration to which he was submitted only showed an anosmia and was otherwise found to be normal. Cranial MRI showed signal alterations in both lower (orbitary) convolutions of the frontal lobes, in the anterior region of the right temporal lobe and in both olfactory nerves. Tests for HIV serology, parotiditis, hepatitis B and C virus, HSV, VZV, Mycoplasma pneumoniae and lues were negative. The acute onset of the anosmia in midst of a picture of febricula and headaches made us suspect the presence of an infectious aetiology, and the alterations found in the neuroimaging could be due to post encephalic lesions, with a special predilection for olfactory areas. CONCLUSIONS: 1. MRI plays a fundamental role in the topographic and aetiological evaluation of olfactory dysfunctions of a central origin; 2. Affectation of the central olfactory passages of an infectious aetiology in a non HIV patient and with neuroimaging findings is a rare complication.

Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice.

Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients.