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David G Munoz

Publications and source records attributed to David G Munoz.

At least 19 recordsLinked to original sources
PubMed2006

Validation of the seven-minute screen neurocognitive battery for the diagnosis of dementia in a Spanish population-based sample.

OBJECTIVE: To validate the Seven-Minute Screen Neurocognitive Battery (7MS) in an elderly population-based sample to identify dementia using a new scoring method. METHODS: Five hundred and twenty-seven home-dwelling elderly were assessed with a neurological and neuropsychological exam. The total score of the 7MS was the sum of z scores of its subtests. Dementia was diagnosed according to DSM-IV. The ROC curve and the diagnostic parameters of the 7MS were calculated. RESULTS: The 7MS could be fully applied in 416 cases (78.9%), and 48 were diagnosed as demented independently of the 7MS. The four 7MS subtests correctly classified 97.6% of cases by discriminant analysis; orientation and memory were the most discriminative. Factorial analysis showed a single dimension in the 7MS. The ROC curve area for diagnosis of dementia was 0.996 (95% CI 0.992-1), sensitivity 100%, specificity 95.1%, and diagnostic accuracy 96.8%. All these parameters were higher than those of other cognitive screening tests. Dementia explained 54.9% of the variance of the 7MS, and age 3.1%; sex and education did not have a significant effect. CONCLUSIONS: The 7MS is a valid tool for the diagnosis of dementia, even when cognitive decline is mild, although it may not be appropriate for extensive epidemiological surveys.

Aged↗
PubMed2006

Postmortem examination of vascular lesions in cognitive impairment: a survey among neuropathological services.

BACKGROUND AND PURPOSE: A full appreciation of the presence of cerebral vascular lesions in cognitively impaired patients can be ultimately reached at the neuropathological level. However, there are no detailed guidelines regarding what neuropathologists should look for at autopsy in cases of suspected vascular dementia or vascular cognitive impairment. We aimed at surveying the postmortem neuropathological procedures used in different centers in examining brain lesions of presumable or possible vascular origin in cognitively impaired patients. METHODS: Thirteen laboratories participated in the survey by filling in a semistructured questionnaire. We reviewed sampling and histology procedures in use and the neuropathological definitions of some of these lesions. Neuropathological criteria for the definition of a vascular origin of the dementing process were also surveyed. RESULTS: A large variability across centers was observed in the procedures used for the neuropathological examination and the histology techniques. Heterogeneity existed also in the definition of commonly found lesions (eg, white matter alterations, small vessel disease), interpretation of whether or not the lesions were reputed to be of vascular origin, and consequently in the interpretation of the cause of cognitive decline. CONCLUSIONS: The appreciation of the presence of neuropathologically verified vascular lesions in cognitively impaired cases may be heavily influenced by the laboratory tools used and also by the heterogeneity of the criteria applied in different centers. Harmonization of neuropathological procedures is badly needed in the field of vascular dementia and vascular cognitive impairment to better understand the association between various vascular lesions and clinical symptoms such as cognitive impairment.

Artifacts↗
PubMed2005

The evolution and pathology of frontotemporal dementia.

This is a clinicopathologic study of a prospective, clinic-based cohort of patients with frontotemporal dementia (FTD)/Pick complex, who were followed to autopsy. A total of 60 patients with the clinical syndromes of the behavioural variant of FTD (FTD-bv) (n = 32), primary progressive aphasia (PPA) (n = 22), corticobasal degeneration syndrome (CBDS) (n = 4) and progressive supranuclear palsy (PSP) (n = 2) at onset, referred to a cognitive neurology clinic who had subsequent post-mortem examination were included. The most common histological variety was motor neurone disease type inclusion (MNDI) (n = 18), followed by corticobasal degeneration (CBD) (n = 12), then Pick's disease (n = 6), dementia lacking distinctive histology (DLDH) (n = 6) and PSP (n = 3). Others fulfilled the histological criteria for Alzheimer's disease combined with glial pathology (n = 6), Alzheimer's disease only (n = 4), Lewy body variant (n = 2), prion disease (n = 1), vascular dementia (n = 1) and undetermined (n = 1). The most common first syndrome among the MNDI and DLDH (tau negative) pathologies was FTD-bv, but subsequently progressive aphasia (PA), occasionally CBDS and semantic dementia also developed. Tau positive histologies of CBD, PSP and Pick bodies were most frequently associated with PPA onset or CBDS/PSP, but behavioural symptoms were also common. Age of onset was earlier in tau negative cases, but the duration of illness and gender distribution were about the same in all histological variants. Although the tau negative and positive histologies are predicted to some extent by the clinical onset, the extent of the overlap and the convergence of the syndromes in the course of the disease argue in favour of maintaining the clinical and pathological varieties under a single umbrella.

Adult↗
PubMed2005

A multigenerational pedigree of late-onset Alzheimer's disease implies new genetic causes.

We describe the clinical phenotype and pathology of a new autosomal dominant late-onset familial form of Alzheimer's disease in four extensive kindred originated in a genetically isolated population. Twelve affected and 16 unaffected members of these kindred were examined clinically, and a brain post-mortem study was carried out in one case. The preliminary genetic assessment included complex segregation analysis, evaluation of the power to detect linkage, and exclusion of candidate genes. Dementia has been recorded for six generations in ancestors of examined cases. Review of death certificates allowed linking of all subjects in four extensive pedigrees. Affected individuals examined had progressive memory loss with onset between 57 and 74 years of age, along with seizures, myoclonus and parkinsonism in advanced stages. The brain of the case examined post-mortem showed widespread neocortical neuritic plaques and neurofibrillary tangles (stage VI of Braak), amyloid angiopathy, and Lewy bodies restricted to limbic areas. Sequencing exons 16 and 17 of amyloid precursor protein, and exons 4-12 of presenilin 1 and presenilin 2 genes did not disclose any mutations. Genotyping with markers D21S265, D14S71, D14S77, D1S2850 and D1S479 located 1-3 cM from the previously reported genes further excluded linkage to these genes. Seven out of 12 cases were apolipoprotein E (APOE) epsilon3/3, although the presence of an APOE epsilon4 allele was associated with an increased risk of dementia (odd ratio 6.17; 95% confidence interval: 1.15-33.15), but not to an earlier age of onset. Complex segregation analysis showed that the best model fitting the data was that of a major gene (dominant) with a gene frequency close to 3% in this population. Simulation analysis predicted an average logarithm of odds (LOD) of 2.2 at = 0.05. These four families, which seem to be part of a common extended pedigree originated by a founder arriving in this region in the 18th century, represent an autosomal dominant late-onset familial Alzheimer's disease not linked to previously known genetic loci. The simulation analysis suggests that it will be feasible to locate a novel responsible gene in these kindred.

Age of Onset↗
PubMed2004

Alzheimer's disease with and without cerebral infarcts.

OBJECTIVE: To compare the clinical and pathological features of Alzheimer's disease (AD) patients with and without associated cerebral infarcts (CI). METHODS: The consecutive records of 57 prospectively studied demented patients fulfilling the CERAD criteria for the pathological diagnosis of AD were reviewed. Cases with cortical Lewy bodies were excluded. CI were found in 22 cases (39%) (AD+CI group): large infarcts (5), lacunes (13) and/or hippocampal sclerosis (4), and were absent in 35 cases (AD group). Microscopic infarcts, cribiform change, amyloid angiopathy, and white matter rarefaction were not considered in this classification, but were quantified. Cortical atrophy, neurofibrillary tangle and senile plaque (diffuse and neuritic) load were also measured. Pathological evaluation was independent of clinical information. Clinical and pathological data were compared between both groups. RESULTS: AD+CI cases were significantly older, more commonly female, less educated, and more often had blue collar occupations, sleep disturbances, frontal release signs, and EEG spikes than AD cases. Other differences found (acute/subacute onset, behavioral disturbances, and leukoaraiosis on CT scan) disappeared after controlling for age. The frequency of known vascular risk factors and focal motor and sensory signs did not differ between the groups, which showed remarkable clinical similarity overall. The only significant differences on pathological exam were hippocampal microinfarcts and white matter lesions, although there was a trend for lower neurodegenerative lesion load in the AD+CI group. The ischemic lesions were located in temporal lobe in 50% of AD+CI patients; these cases had a significantly lower neocortical neurodegenerative lesion load than those with CI in other sites. CONCLUSIONS: The presence of CI in AD increases significantly with age, but has scarce influence on the clinical features, and cannot be predicted from common vascular risk factors. In spite of a trend, there are no major differences in neurodegenerative lesion load between AD and AD+CI groups, except when CI are located in the temporal lobe (including hippocampus), suggesting that this location may be important in the physiopathology of mixed vascular and AD dementia.

Age Factors↗
PubMed2004

Intranuclear rodlets in the substantia nigra: interactions with marinesco bodies, ubiquitin, and promyelocytic leukemia protein.

There is growing appreciation that the nucleus is organized into an array of discrete structural domains, each subserving a specific function. These functional nuclear bodies are to be distinguished from pathological intranuclear inclusions which have been described in a variety of neurodegenerative diseases. Marinesco bodies (MBs) are eosinophilic ubiquitinated intranuclear inclusions found in pigmented neurons of the human substantia nigra and locus coeruleus. Traditionally considered non-pathological entities, more recent studies have indicated that MBs are associated with the age-associated degenerative changes in the substantia nigra and striatal loss of dopaminergic terminals. In the present morphological study of the human substantia nigra, we demonstrate colocalization, contiguity, and focally shared immunoreactivity between MBs and neuronal intranuclear rodlets (INRs). The latter nuclear structures of uncertain function are markedly decreased in the cortex of Alzheimer's disease, but not dementia with Lewy bodies. In addition, we demonstrate an interaction between INRs and promyelocytic leukemia (PML) protein, the signature protein of PML nuclear bodies. These results suggest that structures which subserve the functional compartmentalization of the neuronal nucleus may be relevant to elucidating cellular mechanisms of age-related motor dysfunction.

Aged↗
PubMed2004

Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies.

OBJECTIVE: This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies. METHOD: The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer's Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer's disease studied prospectively during life. RESULTS: The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy body staging was associated with the presence of persistent visual hallucinations and persistent delusions. All baseline psychiatric features were significantly more frequent in dementia with Lewy bodies than in Alzheimer's disease, as were persistent visual hallucinations, but patients who had dementia with Lewy bodies and severe tangle pathology had a clinical symptom profile more similar to that of Alzheimer's disease patients and were less likely to have neocortical Lewy bodies. CONCLUSIONS: The modest proportion of patients with Lewy body dementia and more severe tangle pathology resembled Alzheimer's disease patients clinically. Unlike Alzheimer's disease, dementia with Lewy bodies showed a significant inverse association between tangle burden and psychosis.

Aged↗
PubMed2003

Primary progressive aphasia and Pick complex.

Ten autopsied patients from a prospectively followed, clinically defined, neuropsychologically and radiologically documented cohort with primary progressive aphasia were histologically characterized. All were variants of frontotemporal degeneration (Pick complex): Pick body dementia, n=3, corticobasals degeneration (CBD), n=4, and tau and synuclein negative ubiquitinated inclusions of the motor neuron disease type, n=3. All shared superficial cortical spongiosis, neuronal loss, and gliosis. Although most patients had fluent anomic aphasia at onset, all progressed to a nonfluent or mute state. Comprehension, episodic memory, and activities of daily living were initially preserved. Three cases with Pick body dementia had verbal apraxia and stuttering at onset. Two of the patients with CBD pathology were older than the average primary progressive aphasia (PPA). All patients developed secondary syndromes either of frontotemporal dementia (FTD) and/or extrapyramidal-apraxic manifestations (CBD). By the time autopsy was obtained, the pathology appeared outside the language areas. Progressive aphasias secondary to Alzheimer's disease (AD) were excluded on the basis of early loss of memory and comprehension.Rather than the previously emphasized histological heterogeneity, clinically probable PPA has a predictive value of a group of related pathologies, collectively named frontotemporal degeneration, or Pick complex. This series of autopsied cases provides evidence for the clinical and pathological overlap of PPA with FTD and CBD, and contributes to the diagnostic and neuropsychological definition of PPA.

Aphasia↗
PubMed2003

Small vessel disease: neuropathology.

Diseases of small cerebral blood vessels are heterogeneous in etiology and manifestations. Lipohyalinosis, venous collagenosis, amyloid angiopathy, and CADASIL affect different populations of blood vessels. Large and small hemorrhages, lacunae, cortical microinfarcts, and leukoaraiosis are the most important consequences of the small vessel angiopathies. Altered permeability as well as ischemia may be involved in the pathogenesis of the latter.

Aged↗
PubMed2003

Rates of cognitive decline in Alzheimer's disease and dementia with Lewy bodies.

Increased interest in types of dementia has developed as more cases are identified in aging populations. Here we compare the rates of cognitive decline over time in three groups with dementia from the University of Western Ontario Dementia Study: Alzheimer's disease (AD), dementia with Lewy bodies and a group with both AD and Lewy bodies. All diagnoses were verified by autopsy using standard diagnostic methods. Cognitive impairment was measured with the Extended Scale for Dementia (ESD). Members of each group with dementia were age and sex matched with individuals without dementia as controls. The 15 cases of AD, 7 cases with Lewy bodies and 8 cases with both conditions were all free of significant vascular disease. Linear regression was used to determine the rate of changes in ESD scores over time in months. All three control groups showed no change in cognitive status over time. As expected, all groups with dementia showed progressive cognitive impairment. Analysis of the slope parameter showed that all groups deteriorated at the same rate of approximately 2 ESD points per month. Quadratic models fit better than simple linear models in all groups. Results suggest that the final rate of cognitive decline in dementia may not necessarily reflect the underlying cause.

Aged↗
PubMed2002

Frontotemporal dementia.

Frontotemporal dementia is a new name for clinical Pick's disease; the eponymic term PiD has been increasingly restricted to the pathologic variant with Pick bodies. This article describes the clinical picture, pathology, and genetic mechanisms of frontal lobe dementia. Frontotemporal dementia is still under-diagnosed and underestimated, partly because the individual components of the complex are considered separately or are considered "heterogeneous," a somewhat misleading adjective used in many descriptions. This article emphasizes the considerable overlap among the different varieties of frontotemporal dementia, as well as the distinctive features of each.

Aphasia, Primary Progressive↗