Showing papers by "Mario F. Mendez published in 2021"

The Relationship Between Anxiety and Alzheimer's Disease.

Abstract: Although Alzheimer's disease (AD) is primarily a neurocognitive disorder, it also results in prominent neuropsychiatric symptoms (NPS). Much literature has investigated the NPS of apathy and depression in association with AD, but relatively less is known regarding anxiety, the third most common NPS in this disorder. The prevalence of anxiety symptoms in AD is about 40%, and it can be a prelude of AD. Anxiety can be especially present among patients with mild cognitive impairment, mild dementia, or early-onset forms of the disease, and can promote progression or conversion to Alzheimer's clinical syndrome. A number of studies have established that anxiety is associated with positive amyloid scans, mesial temporal changes with atrophy and hypometabolism in the entorhinal region, and neurofibrillary tangles present on pathological examination of this region. In addition to psychosocial factors, proposed neurobiological mechanisms for increased anxiety in AD include decreased sensorimotor gating, relatively increased activation of amygdalae or the Salience Network, and the presence of comorbid pathology, particularly Lewy bodies. Having management strategies for anxiety in patients with AD is important as anxiety can worsen cognitive deficits. Interventions involve psychological support, behavioral management, and the judicious use of the psychiatric armamentarium of medications.

Brain volumetric deficits in MAPT mutation carriers: A multisite study

Abstract: Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

Abstract: Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18 F]Florbetaben and [18 F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

Benson's Disease or Posterior Cortical Atrophy, Revisited.

Abstract: Background D. Frank Benson and colleagues first described the clinical and neuropathological features of posterior cortical atrophy (PCA) from patients in the UCLA Neurobehavior Program. Objective We reviewed the Program's subsequent clinical experience with PCA, and its potential for clarifying this relatively rare syndrome in comparison to the accumulated literature on PCA. Methods Using the original criteria derived from this clinic, 65 patients with neuroimaging-supported PCA were diagnosed between 1995 and 2020. Results On presentation, most had visual localization complaints and related visuospatial symptoms, but nearly half had memory complaints followed by symptoms of depression. Neurobehavioral testing showed predominant difficulty with visuospatial constructions, Gerstmann's syndrome, and Balint's syndrome, but also impaired memory and naming. On retrospective application of the current Consensus Criteria for PCA, 59 (91%) met PCA criteria with a modification allowing for "significantly greater visuospatial over memory and naming deficits." There were 37 deaths (56.9%) with the median overall survival of 10.3 years (95% CI: 9.6-13.6 years), consistent with a slow neurodegenerative disorder in most patients. Conclusion Together, these findings recommend modifying the PCA criteria for "relatively spared" memory, language, and behavior to include secondary memory and naming difficulty and depression, with increased emphasis on the presence of Gerstmann's and Balint's syndromes.

Cotard syndrome in anti-NMDAR encephalitis: two patients and insights from molecular imaging.

Abstract: Cotard syndrome is a clinical condition defined by the presence of nihilistic delusions. We report two patients with Cotard syndrome in whom anti-NMDAR encephalitis (ANMDARE) was confirmed. Both ca...

Degenerative dementias: Alterations of emotions and mood disorders.

Abstract: Degenerative dementias such as Alzheimer's disease and frontotemporal dementia result in distinct alterations in emotional processing, emotional experiences, and mood. The neuropathology of these dementias extends to structures involved in emotional processing, including the basolateral limbic network (orbitofrontal cortex, anterior temporal lobe, amygdala, and thalamus), the insula, and ventromedial frontal lobe. Depression is the most common emotion and mood disorder affecting patients with Alzheimer's disease. The onset of depression can be a prodromal sign of this dementia. Anxiety can also be present early in the course of Alzheimer's disease and especially among patients with early-onset forms of the disease. In contrast, patients with behavioral variant frontotemporal dementia demonstrate hypoemotionality, deficits in the recognition of emotion, and decreased psychophysiological reactivity to emotional stimuli. They typically have a disproportionate impairment in emotional and cognitive empathy. One other unique feature of behavioral variant frontotemporal dementia is the frequent occurrence of bipolar disorder. The management strategies for these alterations of emotion and mood in degenerative dementias primarily involve the judicious use of the psychiatric armamentarium of medications.

Frontotemporal Dementia: A Window to Alexithymia.

Abstract: Alexithymia is pervasive among psychiatric patients, but its neurobiological mechanism is unclear Patients with alexithymia cannot "read emotions," a process involving interoception, or the perception of the body's internal state, primarily in the insulae The frontotemporal dementias are also associated with inability to correctly read emotions; hence, these dementias can provide a window into the mechanism of alexithymia Patients with behavioral variant frontotemporal dementia (bvFTD) have a weak emotional signal with impaired emotional recognition, hypoemotionality, and decreased physiological arousal bvFTD affects the insulae, and the weak emotional signal facilitates impaired interoceptive accuracy, resulting in an overreliance on cognitive appraisal rather than on internal sensations In contrast, patients with semantic dementia, another frontotemporal dementia syndrome, can have intact interoception, but they have disturbed cognitive appraisal of the meaning of their bodily sensations This "alexisomia" in semantic dementia can lead to misinterpreted somatic symptoms Together, the findings in alexithymic patients and frontotemporal dementia syndromes support the model of impaired interoceptive accuracy as the mechanism of alexithymia, possibly from dysfunction in the insulae

Quantitative MRI Differences Between Early versus Late Onset Alzheimer's Disease.

Abstract: Investigators report greater parietal tau deposition and alternate frontoparietal network involvement in early onset Alzheimer’s Disease (EOAD) with onset <65 years as compared with typical late on...

The contribution of behavioral features to caregiver burden in FTLD spectrum disorders.

Abstract: Introduction Caregivers of patients with frontotemporal lobar degeneration (FTLD) spectrum disorders experience tremendous burden, which has been associated with the neuropsychiatric and behavioral features of the disorders. Methods In a sample of 558 participants with FTLD spectrum disorders, we performed multiple-variable regressions to identify the behavioral features that were most strongly associated with caregiver burden, as measured by the Zarit Burden Interview, at each stage of disease. Results Apathy and disinhibition, as rated by both clinicians and caregivers, as well as clinician-rated psychosis, showed the strongest associations with caregiver burden, a pattern that was consistent when participants were separated cross-sectionally by disease stage. In addition, behavioral features appeared to contribute most to caregiver burden in patients with early dementia. Discussion Caregivers should be provided with early education on the management of the behavioral features of FTLD spectrum disorders. Interventions targeting apathy, disinhibition, and psychosis may be most useful to reduce caregiver burden.