Aditi Joshi

Nonamnestic Presentations of Early-Onset Alzheimer’s Disease

Early-onset Alzheimer’s disease (EOAD) beginning before the age of 65 may differ from late-onset AD (LOAD) in clinical course and frequency of nonamnestic presentations. In a 10-year retrospective review, 125 patients with EOAD, diagnosed clinically and verified by functional neuroimaging, were compared with 56 patients with LOAD and further classified depending on predominant cognitive difficulty on presentation. Eighty (64%) of the patients with EOAD had a nonamnestic presentation, compared with only 7 (12.5%) of the patients with LOAD. Compared with LOAD, the patients with EOAD had a shorter duration with lower Mini-Mental State Examination scores. The neuroimaging reports among the patients with EOAD showed more hippocampal atrophy with an amnestic presentation, more left parietal changes with impaired language presentations, and more right parietal and occipital changes with impaired visuospatial presentations. These findings indicate that EOAD differs from LOAD in a more aggressive course and in having predominantly nonamnestic presentations that vary in neuropathological location.

Clinicopathologic differences among patients with behavioral variant frontotemporal dementia.

Objective: To characterize the presenting symptoms and signs of patients clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and who had different neuropathologic findings on autopsy. Methods: This study reviewed all patients entered as clinical bvFTD in the National Alzheimers Coordinating Centers database and who had both clinical and neuropathologic data from 2005 to 2011. Among the 107 patients identified, 95 had unambiguous pathologic findings, including 74 with frontotemporal lobar degeneration (bvFTD-FTLD) and 21 with Alzheimer disease (bvFTD-AD). The patients with bvFTD-FTLD were further subdivided into τ-positive (n = 23) or τ-negative (n = 51) histopathology subgroups. Presenting clinical signs and symptoms were compared between these neuropathologic groups. Results: The patients with bvFTD-FTLD were significantly more likely than patients with bvFTD-AD to have initially predominant personality changes and poor judgment/decision-making. In contrast, patients with bvFTD-AD were more likely than patients with bvFTD-FTLD to have memory difficulty and delusions/hallucinations and agitation. Within the bvFTD-FTLD group, the τ-positive subgroup had more patients with initial behavioral problems and personality change than the τ-negative subgroup, who, in turn, had more patients with initial cognitive impairment and speech problems. Conclusion: During life, patients with AD pathology may be misdiagnosed with bvFTD if they have an early age at onset and prominent neuropsychiatric features despite having greater memory difficulties and more intact personality and executive functions than patients with bvFTD-FTLD. Among those with FTLD pathology, patients with τ-positive bvFTD were likely to present with behavior/personality changes. These findings offer clues for antemortem recognition of neuropathologic subtypes of bvFTD.

Skin Conductance Levels May Reflect Emotional Blunting in Behavioral Variant Frontotemporal Dementia

Emotional blunting is a core diagnostic feature of behavioral variant frontotemporal dementia (bvFTD). The authors evaluated skin conductance as a measure of emotional blunting among 10 patients with bvFTD compared with 10 with Alzheimers disease and 14 healthy control subjects. Despite responses to an auditory startle stimulus, skin conductance levels (SCLs) were lower in the patients with bvFTD compared with the other groups. The low SCLs significantly correlated with ratings of emotional blunting. The authors conclude that low SCLs in bvFTD indicate a low resting sympathetic state and low emotional arousal. The measurement of SCLs may be a useful noninvasive diagnostic test for bvFTD.

A Scale of Socioemotional Dysfunction in Frontotemporal Dementia

Early social dysfunction is a hallmark symptom of behavioral variant frontotemporal dementia (bvFTD); however, validated measures for assessing social deficits in dementia are needed. The purpose of the current study was to examine the utility of a novel informant-based measure of social impairment, the Socioemotional Dysfunction Scale (SDS) in early-onset dementia. Sixteen bvFTD and 18 early-onset Alzheimers disease (EOAD) participants received standard clinical neuropsychological measures and neuroimaging. Caregiver informants were administered the SDS. Individuals with bvFTD exhibited greater social dysfunction on the SDS compared with the EOAD group; t(32) = 6.32, p < .001. The scale demonstrated preliminary evidence for discriminating these frequently misdiagnosed groups (area under the curve = 0.920, p = <.001) and internal consistency α = 0.977. The SDS demonstrated initial evidence as an effective measure for detecting abnormal social behavior and discriminating bvFTD from EOAD. Future validation is recommended in larger and more diverse patient groups.

Virtual reality for the assessment of frontotemporal dementia, a feasibility study

Abstract Purpose: Behavioral variant frontotemporal dementia (bvFTD) is a non-Alzheimer dementia characterized by difficulty in documenting social-emotional changes. Few investigations have used virtual reality (VR) for documentation and rehabilitation of non-Alzheimer dementias. Methods: Five bvFTD patients underwent insight interviews while immersed in a virtual environment. They were interviewed by avatars, their answers were recorded, and their heart rates were monitored. They were asked to give ratings of their stress immediately at the beginning and at the end of the session. Results: The patients tolerated the head-mounted display and VR without nausea or disorientation, heart rate changes, or worsening stress ratings. Their insight responses were comparable to real world interviews. All bvFTD patients showed their presence in the VR environment as they moved their heads to face and respond to each avatar’s questions. The bvFTD patients tended to greater verbal elaboration of answers with larger mean length of utterances compared to their real world interviews. Conclusions: VR is feasible and well-tolerated in bvFTD. These patients may have VR responses comparable to real world performance and they may display a presence in the virtual environment which could even facilitate assessment. Further research can explore the promise of VR for the evaluation and rehabilitation of dementias beyond Alzheimers disease. Implications for Rehabilitation Clinicians need effective evaluation and rehabilitation strategies for dementia, a neurological syndrome of epidemic proportions and a leading cause of disability. Memory and cognitive deficits are the major disabilities and targets for rehabilitation in Alzheimers disease, the most common dementia. In contrast, social and emotional disturbances are the major disabilities and targets for rehabilitation in behavioral variant frontotemporal dementia (bvFTD), an incompletely understood non-Alzheimer dementia. Virtual reality is a technology that holds great promise for the evaluation and rehabilitation of patients with bvFTD and other non-Alzheimer dementias, and preliminary evidence suggests that this technology is feasible in patients with bvFTD.

White Matter Changes Associated with Resting Sympathetic Tone in Frontotemporal Dementia vs. Alzheimer’s Disease

Background Resting sympathetic tone, a measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD) and other frontally-predominant disorders. Objective To identify the neuroanatomical correlates of skin conductance levels (SCLs), an index of resting sympathetic tone and apathy, among patients with bvFTD, where SCLs is decreased, compared to those with Alzheimer’s disease (AD), where it is not. Methods This study analyzed bvFTD (n = 14) patients and a comparison group with early-onset AD (n = 19). We compared their resting SCLs with gray matter and white matter regions of interest and white matter measures of fiber integrity on magnetic resonance imaging and diffusion tensor imaging. Results As expected, bvFTD patients, compared to AD patients, had lower SCLs, which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity (fractional anisotropy and mean diffusivity) in frontal-anterior temporal regions. After controlling for group membership, the SCLs were significantly correlated with white matter volumes in the cingulum and inferior parietal region in the right hemisphere. Conclusion Among dementia patients, SCLs, and resting sympathetic tone, may correlate with quantity of white matter, rather than with gray matter or with white matter fiber integrity. Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of bvFTD and related disorders.

Stress Reactivity in Traditional Chinese Medicine–Based Subgroups of Patients with Irritable Bowel Syndrome

OBJECTIVES This study aimed to examine differences in autonomic responses to stress, pain perception, and the role of negative affect in these responses in individuals with irritable bowel syndrome (IBS) according to Traditional Chinese Medicine (TCM) classifications. DESIGN Fifty-nine female patients with IBS age 18-65 years diagnosed by TCM practitioners as showing primarily an excess (n=32) or an overlap (n=27) pattern (mixed excess and deficiency) were assessed for symptom differences, heart rate, and skin conductance responses to a psychosocial stressor and pain perception. SETTINGS/LOCATIONS: University of California in Los Angeles, California. RESULTS Compared with the excess group, the overlap group showed significantly greater overall gastrointestinal symptom severity, abdominal pain, and negative affect. The excess group with higher levels of negative affect showed greater reactivity to stress, whereas the overlap group showed an opposite response pattern. The overlap group showed increased cold sensitivity. CONCLUSIONS IBS patients with the overlap pattern have greater disease severity and comorbidity than those with excess alone. Those with excess showed a pattern of increased stress response with greater negative affect, whereas the overlap group with greater deficiency showed lower physiologic arousal with greater negative affect, consistent with depletion resulting from allostatic load.

Hippocampal and Mesial Temporal Sclerosis in Early-Onset Frontotemporal Lobar Degeneration Versus Alzheimer’s Disease

Hippocampal sclerosis (HS) and mesial temporal sclerosis (MTS) may occur with frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) as well as with normal aging. Prior studies suggest that HS/MTS may be more closely associated with FTLD but have not directly compared the prevalence and clinical characteristics of HS/MTS between neuropathologically confirmed early-onset (age ≤ 65) cohorts of FTLD and AD. We identified patients with early-onset FTLD (n = 136) and AD (n = 267) from National Alzheimer’s Center Consortium databases and compared neuropathological and clinical data between these 2 groups. The FTLD group had a significantly higher prevalence of HS/MTS than that of the AD group. However, HS/MTS was associated with increasing age and memory impairment in the AD group but not in the FTLD group. These findings are consistent with the hypothesis that HS/MTS in FTLD occurs as part of the primary pathological process, rather than as a secondary, nonspecific effect of aging on memory and hippocampal function.