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Mario F Mendez

Publications and source records attributed to Mario F Mendez.

At least 19 recordsLinked to original sources
PubMed2025

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders.

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker. METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change. RESULTS: Compared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology. CONCLUSIONS: Our head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.

Humans↗
PubMed2007

Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia.

OBJECTIVE: The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia (FTD). METHODS: Twelve patients with FTD who received donepezil for six months were compared with 12 FTD controls on behavioral measures. RESULTS: The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the FTD Inventory. Four treated patients had increased disinhibited or compulsive acts, which abated with discontinuation of the medication. CONCLUSION: There were no changes in global cognitive performance or dementia severity; however, a subgroup of patients with FTD can experience worsening of symptoms with donepezil.

Behavioral Symptoms↗
PubMed2006

The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families.

Nine families with autosomal dominant Alzheimer's disease (AD), all of whom had the Ala431Glu substitution in the PSEN1 gene and came from Jalisco State in Mexico, have been previously reported. As they shared highly polymorphic flanking dinucleotide marker alleles, this strongly suggests that this mutation arose from a common founder. In the current letter, we expand this observation by describing an additional 15 independent families with the Ala431Glu substitution in the PSEN1 gene and conclude that this mutation is not an uncommon cause of early-onset autosomal dominant AD in persons of Mexican origin.

Adult↗
PubMed2006

What frontotemporal dementia reveals about the neurobiological basis of morality.

There is evidence that moral behavior is a product of evolution and an innate aspect of the human brain. Functional magnetic resonance studies in normals, investigations of psychopaths, and acquired sociopathy from brain lesions suggest a neurobiology of moral behavior. Reports of sociopathy among patients with frontotemporal dementia (FTD) have provided a further opportunity to clarify the neurobiology of morality. They confirm a morality network that includes the ventromedial frontal cortex, the orbitofrontal cortex, and the amygdalae. The right ventromedial region is critical for the emotional tagging of moral situations, the orbitofrontal cortex responds to social cues and mitigates impulsive reactions, and the amygdalae are necessary for threat detection and moral learning. Alterations in moral behavior in FTD may result from a loss of the emotional label of moral dilemmas, coupled with disinhibited responses. More investigations are needed to fully understand how the brain mediates moral or ethical behavior.

Amygdala↗
PubMed2006

The scale for emotional blunting in patients with frontotemporal dementia.

Emotional blunting may underlie many of the behavioral features of frontotemporal dementia (FTD). The Scale for Emotional Blunting (SEB) was evaluated in 12 patients with early FTD, 12 patients with Alzheimer's disease (AD), and 12 normal controls. There were overall group differences on the SEB, and the FTD patients had greater emotional blunting than the AD patients. The SEB had good inter-rater reliability and a sensitivity of 92%, and a specificity of 83.5% for FTD. These findings suggest that the SEB may be a good instrument for the early detection and quantification of emotional blunting in patient with FTD.

Aged↗
PubMed2006

Acquired extroversion associated with bitemporal variant of frontotemporal dementia.

Frontotemporal dementia (FTD) is characterized by alterations in personality. The nature of the personality changes depend on the localization of the pathology. The authors present three patients with acquired extroversion who met criteria for FTD. All three patients exhibited predominant bilateral temporal involvement as determined with functional neuroimaging. Possible mechanisms for acquired extroversion in bitemporal FTD include bilateral amygdalar damage with decreased interpersonal fear or sense of threat, orbitofrontal-ventromedial damage with social disinhibition, and relative sparing of dorsolateral frontal and anterior cingulate regions with preserved interpersonal agency. FTD can be a vehicle for unraveling the basis of personality characteristics such as the introversion/extroversion dimension.

Aged↗
PubMed2006

Depressive and memory symptoms as presenting features of spinocerebellar ataxia.

The spinocerebellar ataxias (SCA) can be manifested in neuropsychiatric symptoms. Among 76 SCA patients presenting to a university ataxia center, depressive symptoms characterized SCA3. Memory symptoms occurred across all SCA groups with relative sparing of SCA6. These differences in neuropsychiatric symptoms suggest the subtype of SCA and the corresponding neuropathological involvement.

Adult↗
PubMed2005

Early-onset dementia: frequency and causes compared to late-onset dementia.

BACKGROUND: Research on the epidemiology of dementia has focused on the elderly. Few investigations have studied differences in etiologic frequencies between early-onset dementia (EOD), with onset at an age of less than 65 years old, and the more common late-onset disorder. OBJECTIVES: To determine relative frequencies and characteristics of EOD versus late-onset dementia (LOD; age of onset > or =65 years) diagnosed in a large memory disorders program over a 4-year period. METHODS: We reviewed medical records, including an extensive neurobehavioral and neurological evaluation, of all patients seen at a large Veteran's Affairs Medical Center Memory Disorders clinic between 2001 and 2004 and assessed demographic variables, final diagnoses, presence of dementia, and differential diagnosis of dementing illnesses. RESULTS: Among 1,683 patients presenting for evaluation of an acquired decline in memory or cognition, 948 (56%) met established clinical criteria for a dementing illness. About 30% (n = 278) of these had an age of onset of <65 years, compared to 670 with LOD. Patients were predominantly male (98%). Compared to the late-onset group, the EOD patients were less severely impaired on presentation, but they did not differ in gender distribution or educational background. The EOD group had significantly more dementia attributed to traumatic brain injury, alcohol, human immunodeficiency virus (HIV), and frontotemporal lobar degeneration compared to the LOD patients. In contrast, the LOD group had significantly more Alzheimer's disease compared to the EOD group. CONCLUSIONS: This study, conducted at a Veterans Affairs Hospital, is the largest series to date on EOD, and found a previously unexpectedly large number of patients below the age of 65 with cognitive deficits and impaired functioning consequent to head trauma, alcohol abuse, and HIV. These findings highlight the differential distribution and importance of preventable causes of dementia in the young.

Age of Onset↗
PubMed2005

Acquired sociopathy and frontotemporal dementia.

BACKGROUND: It is not understood why some patients with frontotemporal dementia (FTD) manifest sociopathic behavior. OBJECTIVE: To examine the prevalence and characteristics of sociopathic behavior in FTD patients as compared to those with Alzheimer's disease (AD). METHODS AND PARTICIPANTS: We surveyed a group of FTD patients and a group of AD patients for sociopathic behavior, evaluated the characteristics surrounding their acts, and compared the groups on neuropsychological tests and functional neuroimaging. Twenty-eight outpatients with FTD (15 men, 13 women; 61.9+/-7.1 years; Mini-Mental State Examination score 23.6+/-8.1) were compared with 28 patients with clinically probable AD (13 men, 15 women; 66.1+/-9.2 years; Mini-Mental State Examination score 21.3 +/- 5.3). Main outcome measures included: (a) the prevalence of sociopathic acts; (b) a structured interview; (c) neuropsychological tests including the Frontal Assessment Battery, and (d) clinically obtained positron emission tomography or single photon emission tomography scans. RESULTS: Sixteen (57%) of the FTD patients had sociopathic behavior compared to two (7%) of the AD patients (chi(2)=13.84, p<0.001). Sociopathic acts among FTD patients included unsolicited sexual acts, traffic violations, physical assaults, and other unacceptable behaviors. On interview, the FTD patients with sociopathic acts were aware of their behavior and knew that it was wrong but could not prevent themselves from acting impulsively. They claimed subsequent remorse, but they did not act on it or show concern for the consequences. Among FTD patients with sociopathy, neuropsychological assessment showed impaired motor inhibition, and functional neuroimaging showed right frontotemporal involvement. CONCLUSION: The results suggest that sociopathy in FTD results from a combination of diminished emotional concern for the consequences of their acts and disinhibition consequent to right frontotemporal dysfunction. In many jurisdictions, FTD patients with sociopathy would not pass legal criteria for 'not guilty by reason of insanity'.

Aged↗
PubMed2005

Fluent versus nonfluent primary progressive aphasia: a comparison of clinical and functional neuroimaging features.

To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA, the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n=21) and nonfluent (n=26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes.

Aged↗
PubMed2005

Frontotemporal lobar degeneration: demographic characteristics of 353 patients.

BACKGROUND: Until recently, frontotemporal lobar degeneration (FTLD) was considered a rare neurodegenerative disorder that was difficult to diagnose. The publication of consensus criteria for FTLD, however, prompted systematic studies. The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. OBJECTIVE: To compare demographic characteristics of patients in the 3 FTLD subgroups. DESIGN: We compared diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at first visit, education, and neuropathological diagnoses in a large sample of FTLD patients from 3 different university dementia clinics, including 2 neurologic clinics in the United States and 1 psychiatric clinic in Germany. RESULTS: The frontotemporal dementia subgroup represented approximately half of all FTLD diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5 years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0 years). There were significantly more men diagnosed as having frontotemporal dementia (63.5%) and semantic dementia (66.7%) when compared with progressive nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent aphasia). Generally, the demographic features and diagnostic categories of the patient populations across the 3 sites were comparable. There were 68 deaths and 37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive tau-negative inclusions (48.5%), dementia lacking distinctive histopathological features (18.2%), and Pick disease (15.2%) were the most common neuropathological diagnoses. CONCLUSIONS: These findings show that cohorts of patients can be combined using new research criteria for FTLD and demonstrate striking demographic differences among FTLD subgroups. The sex and age-at-onset differences suggest that there may be biological differences among FTLD subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for half of all neuropathological diagnoses.

Adult↗
PubMed2005

Stereotypical movements and frontotemporal dementia.

Stereotypical movements are characteristic of autism or mental retardation but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). In this study, we administered the Abnormal Involuntary Movement Scale (AIMS) to 18 patients with FTD and to 18 patients with the most common form of dementia, Alzheimer's disease (AD). The AIMS scores were gathered at the initial presentation of patients who had not received antipsychotic medications. Compared to the AD patients, the FTD patients had significantly more stereotypical movements, including frequent rubbing behaviors and some self-injurious acts. All the FTD patients with stereotypical movements had compulsive-like behaviors, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor.

Aged↗
PubMed2005

An investigation of moral judgement in frontotemporal dementia.

OBJECTIVE: To investigate the basis of disturbed moral judgment in patients with frontotemporal dementia (FTD). BACKGROUND: FTD is characterized by difficulty in modulating social behavior. Patients lack social propriety and may perform sociopathic acts. In addition, FTD patients often lack empathy for others. These findings suggest alterations in the nature of morality in patients with FTD. METHOD: We administered an inventory of moral knowledge and two moral dilemmas to 26 patients with the frontal variant of FTD, 26 patients with Alzheimer disease (AD), and 26 normal control subjects. The FTD patients met Consensus Criteria for FTD and had corroborative frontal abnormalities on functional neuroimaging. The FTD and AD patients were comparably impaired on dementia measures. RESULTS: All these groups showed the retention of knowledge for moral behavior and the ability to make "impersonal" moral judgments. In contrast, the FTD patients were impaired in their ability to make immediate, emotionally based moral judgments compared with the patients with AD and the normal control subjects. CONCLUSIONS: These findings are consistent with an attenuation of the automatic emotional identification with others that is part of the innate moral sense. Such a disturbance may result from neurodegenerative disease affecting the ventromedial frontal cortex.

Aged↗
PubMed2005

Loss of insight and functional neuroimaging in frontotemporal dementia.

Loss of insight is a diagnostic criterion for frontotemporal dementia. It is associated with hypoperfusion/hypometabolism in the right hemisphere, particularly the frontal lobe. Loss of insight is often an anosodiaphoria (i.e., lack of concern) rather than an anosognosia (i.e., decreased awareness).

Aged↗
PubMed2004

Aphemia-like syndrome from a right supplementary motor area lesion.

Lesions in the left supplementary motor area (SMA) can result in a transcortical motor aphasia with nonfluent spontaneous verbal output and relatively preserved repetition. Reading and writing are proportionally affected. We report a patient with an ischemic lesion in the right SMA. He had impaired articulation and normal repetition plus preserved reading and writing, consistent with an aphemia. This patient supports the dissociation of articulatory fluency and linguistic fluency and suggests that both SMAs affect the initiating of articulatory movements required to produce words whereas the left SMA also affects linguistic aspects of speech.

Articulation Disorders↗