Diagnóstico del deterioro cognitivo vascular y sus principales categorías / Diagnosis of vascular cognitive impairment and its main categories

Objetivo: Revisar los principios actuales para el diagnóstico de las categorías de deterioro cognitivo vascular, con énfasis en la nomenclatura, los criterios diagnósticos y los hallazgos clínico-radiológicos diferenciales. Desarrollo: Los principios para el diagnóstico del deterioro cognitivo vascular han evolucionado, pero los criterios disponibles fueron diseñados básicamente para diferenciar la demencia vascular de la demencia tipo Alzheimer, y para propósitos de investigación. Sin embargo, en la práctica clínica se requieren elementos precisos para: 1) el diagnóstico clínico de la demencia y el deterioro cognitivo leve, 2) la identificación clínica y por neuroimagen de las diversas lesiones cerebrovasculares asociadas con la disfunción cognitiva, y 3) la formulación de una relación etiopatogénica entre el deterioro cognitivo y las lesiones cerebrovasculares. Por esta razón se revisaron los elementos diagnósticos de las categorías de deterioro cognitivo vascular, su clasificación y características más relevantes. Se enfatizó en las características que permiten el diagnóstico de la demencia multi-infarto, la demencia por infarto estratégico, la demencia por enfermedad de pequeño vaso cerebral, la demencia mixta y el deterioro cognitivo leve vascular. Conclusiones: Se requiere de la estandarización, por un grupo multidisciplinario de expertos, de la nomenclatura y criterios para el diagnóstico del espectro completo del deterioro cognitivo vascular, y especialmente para la demencia vascular y sus categorías

Objective: A review of current criteria for the diagnosis of categories related with vascular cognitive impairment, in particular the nomenclature, diagnostic criteria, and differential clinical-radiological findings. Development: The criteria for the diagnosis of vascular cognitive impairment have evolved, but available criteria were designed basically for differentiating between vascular dementia and dementia due to Alzheimer disease, and for research purposes. Nevertheless, in clinical practice precise elements are required for: 1) Clinical diagnosis of dementia and mild cognitive impairment; 2) Clinical and neuroimaging criteria for identification of the various cerebrovascular lesions associated with cognitive dysfunction, and 3) A formulation of the aetiogenic-pathogenic relationship between cognitive impairment and cerebrovascular lesions. For this reason, a review was carried out on the diagnostic elements of vascular cognitive impairment categories, classification, and their most relevant characteristics. It highlights the characteristic for the diagnosis of multi-infarction dementia, strategic single infarct dementia, small vessel disease with dementia, mixed dementia, and vascular mild cognitive impairment. Conclusions: Standardisation is required, by a multidisciplinary expert team, as regards nomenclature and criteria for the diagnosis of the full spectrum associated with vascular cognitive impairment and especially for vascular dementia and its categories

[Metabolic encephalopathy secondary to vitamin D intoxication]. / Encefalopatía metabólica secundaria a intoxicación por vitamina D.

The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

La asociación entre la deficiencia de vitamina D y un mayor riesgo de diversas enfermedades, entre ellas cardiovasculares y autoinmunes, ha aumentado en los últimos años el uso de suplementos para la normalización de los valores plasmáticos de esta vitamina. Desde entonces se ha descrito un mayor número de casos de intoxicación iatrogénica por vitamina D. Presentamos una enferma de 81 años con encefalopatía metabólica e insuficiencia renal secundarias a una intoxicación por vitamina D. Los suplementos orales con calcio y vitamina D se le prescribieron después de sufrir una fractura vertebral osteoporótica. La enferma mejoró clínica y analíticamente tras hidratación y diuréticos. Es importante destacar la hipercalcemia como causa de encefalopatía metabólica y considerar la intoxicación por vitamina D como etiología poco frecuente pero posible de hipercalcemia e insuficiencia renal reversibles.

Association of silent lacunar infarct with brain atrophy and cognitive impairment.

OBJECTIVE: Silent lacunar infarct (SLI) is associated with cognitive decline and linked to an increased risk of stroke and dementia. We examined the association of SLI with MRI measures of cortical thickness, subcortical and lateral ventricular shapes and cognition in 285 ethnic Chinese elderly. METHODS: SLI, cortical thickness, shapes of subcortical and ventricular structures were quantified using MRI. The cognitive performance was assessed using comprehensive neuropsychological tests. Linear regression was used to examine associations among SLI, brain measures and cognition. RESULTS: SLI was associated with atrophy in multiple subcortical structures, ventricular enlargement and widespread cortical thinning. Both SLI and atrophy were independently related to poorer performance in attention, memory and language domains. Only SLI was associated with visuomotor speed and executive function, while atrophy mediated the association between SLI and visuoconstruction. CONCLUSIONS: Our findings support a vascular contribution to neurodegeneration and cognitive impairment.

[Current concepts in vascular dementia]. / Démences vasculaires : concepts actuels.

Vascular dementias, VD, are dementias due to cerebrovascular lesions. Subgroups of VD include multi-infarct dementia, single infarct (or strategic infarct) dementia, subcortical ischemic vascular dementia, hemorrhagic dementia, hypoperfusion dementia. VD are also related to post-stroke dementia, mixed Alzheimer's disease and vascular dementia and vascular cognitive impairment. These various entities allow to characterize more homogenous subgroups within the heterogeneous group of vascular dementias. However, ambiguities in their definitions, associated with frequent overlaps as well as lack of consensual definition for mixed dementia limit both their theoretical value and use in clinical practice. The diagnosis of cerebrovascular diseases should be dissociated from that of dementia, which could be associated with other pathologies.

Prediction of incident dementia: impact of impairment in instrumental activities of daily living and mild cognitive impairment-results from the German study on ageing, cognition, and dementia in primary care patients.

OBJECTIVES: There is an increasing call for a stronger consideration of impairment in instrumental activities of daily living (IADL) in the diagnostic criteria of Mild Cognitive Impairment (MCI) to improve the prediction of dementia. Thus, the aim of the study was to determine the predictive capability of MCI and IADL impairment for incident dementia. DESIGN: Longitudinal cohort study with four assessments at 1.5-year intervals over a period of 4.5 years. SETTING: : Primary care medical record registry sample. PARTICIPANTS: As part of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients, a sample of 3,327 patients from general practitioners, aged 75 years and older, was assessed. MEASUREMENTS: The predictive capability of MCI and IADL impairment for incident dementia was analysed using receiver operating characteristics, Kaplan-Meier survival analyses, and Cox proportional hazards models. RESULTS: MCI and IADL impairment were found to be significantly associated with higher conversion to, shorter time to, and better predictive power for future dementia. Regarding IADL, a significant impact was particularly found for impairment in responsibility for one's own medication, shopping, and housekeeping, and in the ability to use public transport. CONCLUSIONS: Combining MCI with IADL impairment significantly improves the prediction of future dementia. Even though information on a set of risk factors is required to achieve a predictive accuracy for dementia in subjects with MCI being clinically useful, IADL impairment should be a very important element of such a risk factor set.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a single-gene disorder directly affecting the cerebral small blood vessels, that is caused by mutations in the HTRA1 gene encoding HtrA serine peptidase/protease 1 (HTRA1). CARASIL is the second known genetic form of ischemic, nonhypertensive, cerebral small-vessel disease with an identified gene, along with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The exact prevalence of CARASIL is currently unknown, and to date approximately 50 patients have been reported, most of them from Japan and two from China. Genetically, no founder haplotype has been identified, and thus the disease is expected to be found more widely. The main clinical manifestations of CARASIL are ischemic stroke or stepwise deterioration in brain functions, progressive dementia, premature baldness, and attacks of severe low back pain or spondylosis deformans/disk herniation. The most characteristic findings on brain magnetic resonance imaging are diffuse white matter changes and multiple lacunar infarctions in the basal ganglia and thalamus. Histopathologically, CARASIL is characterized by intense arteriosclerosis, mainly in the small penetrating arteries, without granular osmiophilic materials or amyloid deposition. CARASIL is a prototype single-gene disorder of cerebral small vessels secondary to and distinct from CADASIL. CARASIL-associated mutant HTRA1 exhibited decreased protease activity and failed to repress transforming growth factor-ß family signaling, indicating that the increased signaling causes arteriopathy in CARASIL. Therefore, HTRA1 represents another new gene to be considered in future studies of cerebral small-vessel diseases, as well as alopecia and degenerative vertebral/disk diseases.

[Vascular dementia]. / Vaskuläre Demenz.

Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.

Is the clock drawing test appropriate for screening for mild cognitive impairment?--Results of the German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe).

BACKGROUND: Individuals with mild cognitive impairment (MCI) are at high risk of developing dementia and are a target group for preventive interventions. Therefore, research aims at diagnosing MCI at an early stage with short, simple and easily administrable screening tests. Due to the fact that the Clock Drawing Test (CDT) is widely used to screen for dementia, it is questionable whether it is suited to screen for MCI. METHODS: 3,198 primary care patients aged 75+ were divided into two groups according to their cognitive status, assessed by comprehensive neuropsychological testing: individuals without MCI and individuals with MCI. The CDT scores, evaluated by the scoring system of Sunderland et al. [J Am Geriatr Soc 1989;37:725-729], of both groups were compared. Multivariate analyses were calculated and the sensitivity and specificity of the CDT to screen for MCI were reported. RESULTS: Significant differences were found for CDT results: MCI patients obtained worse results than cognitively unimpaired subjects. CDT has a significant impact on the diagnosis of MCI. However, sensitivity and specificity as well as receiver operating characteristic analyses are not adequate, meaning that the CDT could not be named as an exact screening tool. LIMITATIONS: Applying different CDT versions of administration and scoring could yield different results. CONCLUSIONS: CDT does not achieve the quality to screen individuals for MCI.

Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study.

BACKGROUND: The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels. METHODS: A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale. RESULTS: Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatric variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group. CONCLUSIONS: These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.

Patterns of neuropsychological impairment in MCI patients with small subcortical infarcts or hippocampal atrophy.

We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease.

Vascular dementia.

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's dementia (AD). It is characterized by loss of executive function with milder memory loss as compared with AD and is associated with cerebral brain infarction or hemorrhage. Treatment is predominantly focused on cardiovascular risk factor reduction, but anticholinesterase inhibitors and memantine may play a role. The data is most robust for donepezil.

Neuroimaging predictors of cognitive impairment in confluent white matter lesion: volumetric analyses of 99 brain regions.

BACKGROUND: Although confluent white matter lesion (WML) is associated with cognitive impairment, the mechanism explaining this association is controversial. We aimed to investigate comprehensively the MRI predictors of cognitive impairment in confluent WML. METHODS: Among 45 lacunar stroke patients who had confluent WML, we evaluated the association of executive function [Mattis Dementia Rating Scale - Initiation/Perseveration subscale (MDRS I/P)] and global cognition [Mini-Mental State Examination (MMSE)] with the volume of WML, measures of lacunes and microbleeds, and the volumes of 99 other specific brain regions. RESULTS: Regression analyses showed that WML volume predicted performance on the MDRS I/P (beta = -0.34, p = 0.016) independent of age. Volumes of cortical gray matter (cGM; beta = 0.41, p = 0.003), the lateral fronto-orbital gyrus (beta = 0.38, p = 0.01), superior frontal gyrus (beta = 0.29, p = 0.04), lateral ventricle (beta = -0.30, p = 0.04), and posterior limb of the internal capsule (beta = 0.43, p = 0.002) predicted MDRS I/P performance independent of WML volume. Volumes of cGM, and the lateral fronto-orbital gyrus predicted MMSE performance as well. CONCLUSION: Atrophy along the frontosubcortical pathways and cGM predict cognition in confluent WML independent of WML volume.

[Vascular dementia and mixed dementia]. / Démences vasculaires et démences mixtes.

The concept of vascular dementia has evolved over the past century to include multiple underlying pathophysiological mechanisms. Neuroimaging techniques offer new and better ways to identify the presence of cerebrovascular pathology, although they do not improve our ability to link these changes to the onset of clinical cognitive impairment. Clinical criteria for vascular dementia have also evolved but they remain imperfect. Most epidemiological studies define mixed dementia as the coexistence of Alzheimer's disease and vascular dementia. Clinicopathologic correlations show a clear association between the concomitant presence of vascular and Alzheimer lesions and the severity of cognitive impairment in mixed dementia and provide strong support for the validity of the mixed dementia concept. Mixed dementia is a very frequent disease that remains underdiagnosed, especially in the elderly. The diagnosis of vascular and mixed dementia remains a clinical challenge and cannot be improved without further studies of clinicopathological correlations and functional neuroimaging. Preventive therapeutic interventions include control of vascular risk factors and especially treatment of hypertension.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migrane, recurrent stroke, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in -33% of patients. CADASIL is commonly overlooked or misdiagnosed owing to its recent identification. The pathological hallmark of angiopathy is the presence of multiple, small, deep cerebral infarcts, leucoencephalopathy, and nonatherorosclerotic, nonamyloid angiopathy involving mainly small, deep perforating cerebral arteries. Changes also are present in vascular smooth muscle cells and consist in the presence of granular osmiophilic material (GOM). The defective gene in CADASIL is Notch 3, which encodes a large transmembrane receptor. Magnetic resonance imaging shows high intensity signal lesions, often confluent, and areas of cystic degeneration of subcortical white matter and basal ganglia. Diagnostic strategies in CADASIL are matter of discussions because the electron microscopic demonstration of GOM was reported in 100% of symptomatic patients of French authors, but only in 45% of a British study. GOMs are not present in presymptomatic patients.