Eliot A. Licht

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.

Psychotic Symptoms in Frontotemporal Dementia: Prevalence and Review

Background/Aims: Although most patients with frontotemporal dementia (FTD) present with neuropsychiatric symptoms, the frequency of psychotic symptoms is unclear. This study aims to determine the prevalence of psychotic symptoms in a large cohort of well-diagnosed and followed FTD patients compared to age-matched patients with Alzheimer’s disease (AD) and to further review the literature on psychosis in FTD. Methods: Delusions, hallucinations and paranoia were evaluated among 86 patients who met consensus criteria for FTD, had frontotemporal changes on functional neuroimaging and were followed for 2 years. They were compared to 23 patients with early-onset AD on a caregiver-administered psychiatric questionnaire. Results: Among the FTD patients, only 2 (2.3%) had delusions, 1 of whom had paranoid ideation; no FTD patient had hallucinations. This was significantly less than the AD patients, 4 (17.4%) of whom had delusions and paranoia. Other investigations fail to establish a significant association of psychosis with FTD. Conclusions: These findings, and a literature review, indicate that psychotic symptoms are rare in FTD, possibly due to limited temporal-limbic involvement in this disorder.

Cognitive Differences between Early- and Late-Onset Alzheimer's Disease:

Although neuropathologic studies showed that early-onset Alzheimers disease (EAD) and “senile dementia” were indistinguishable, clinical studies suggested that EAD and late-onset Alzheimers disease (LAD) were cognitively distinct. We sought to investigate whether EAD and LAD are cognitively different by comparing patients at the extremes of the ages of onset in order to maximize features that might separate them. We compared 44 men with EAD (age of onset less than 65 years) with 44 men with LAD (age of onset 84 years or older) on an intake cognitive screening examination on initial presentation. The EAD and LAD groups did not differ on dementia or most cognitive variables. Compared with EAD, the LAD group had worse verbal fluency and motor-executive functions. These differences disappeared when age differences were taken into account. We conclude that Alzheimers disease is a clinically heterogeneous disorder whose manifestations can vary with age of onset. These differences indicate age-related vulnerabilities in this disease.

Mild traumatic brain injury from primary blast vs. blunt forces: post-concussion consequences and functional neuroimaging.

INTRODUCTION Primary blast forces may cause dysfunction from mild traumatic brain injury (mTBI). OBJECTIVE To investigate the effects of primary blast forces, independent of associated blunt trauma and post-traumatic stress disorder, on sensitive post-concussive measures. METHODS This study investigated post-concussive symptoms, functional health and well-being, cognition, and positron emission tomography (PET) neuroimaging among 12 Iraq or Afghanistan war veterans who sustained pure blast-force mTBI, compared to 12 who sustained pure blunt-force mTBI. RESULTS Both groups had significantly lower scores than published norms on the Rivermead Post-Concussion Questionnaire (RPQ) and the SF36-V Health Survey. Compared to the Blunt Group, the Blast Group had poorer scores on the Paced Auditory Serial Addition Test (PASAT) and greater PET hypometabolism in the right superior parietal region. Only the Blast Group had significant correlations of their RPQ, SF36-V Mental Composite Score, and PASAT scores with specific regional metabolic changes. CONCLUSION This pilot study suggests that pure blast force mTBI may have greater post-concussive sequelae including deficits in attentional control and regional brain metabolism, compared to blunt mTBI. A disturbance of a right parietal-frontal attentional network is one potential explanation for these findings.

Positron Emission Tomography Facilitates Diagnosis of Early-Onset Alzheimer’s Disease

Background: Clinical positron emission tomography (PET) may help in the evaluation of presenile patients with memory complaints for the presence of Alzheimer’s disease (AD). Methods: Clinical PET scans from 27 patients with clinically probable AD and early ages of onset (<65 years) were compared to PET scans from 27 age-matched controls presenting with memory complaints, but without dementia or mild cognitive impairment. Results: Compared to controls, the AD patients had significant frontal, temporal and parietal hypometabolism bilaterally, and AD diagnosis correlated with left temporal and right temporoparietal hypometabolism. The sensitivity of temporoparietal hypometabolism for AD was 92.6%, the specificity 85.2%. Conclusion: Clinical PET imaging helps distinguish early-onset AD from patients with memory complaints not meeting criteria for dementia or mild cognitive impairment.

Changes in dietary or eating behavior in frontotemporal dementia versus Alzheimer's disease.

Background: Changes in dietary or eating behavior are common in dementia and may help distinguish between different dementing illnesses. Objective: To evaluate and characterize differences in dietary and eating behavior among patients with early frontotemporal dementia (FTD) versus Alzheimers disease (AD). Methods: This study administered the Food-Related Problems Questionnaire (FRPQ) to caregivers of 16 patients with FTD and 16 comparable patients with AD. The FRPQ was evaluated at initial presentation when patients presented for a diagnostic evaluation. Results: Compared with the AD patients, the FTD patients had significantly more changes on the FRPQ. Subscale analysis indicated that the FTD patients showed impairment of observed satiety, improper taking of food, and inappropriate responses when food was not available. Conclusions: The use of food-related questionnaires, such as the FRPQ, can help distinguish FTD patients, early in their course, from those with AD and can further characterize the altered dietary and eating behavior.

Changes in personality after mild traumatic brain injury from primary blast vs. blunt forces

Introduction: Injuries from explosive devices can cause blast-force injuries, including mild traumatic brain injury (mTBI). Objective: This study investigated changes in personality from blast-force mTBI in comparison to blunt-force mTBI. Methods: Clinicians and significant others assessed US veterans who sustained pure blast-force mTBI (n = 12), as compared to those who sustained pure blunt-force mTBI (n = 12). Inclusion criteria included absence of any mixed blast–blunt trauma and absence of post-traumatic stress disorder. Measures included the Interpersonal Measure of Psychopathy (IM-P), the Big Five Inventory (BFI), the Interpersonal Adjectives Scale (IAS) and the Frontal Systems Behaviour Scale (FrSBe). Results: There were no group differences on demographic or TBI-related variables. Compared to the Blunt Group, the Blast Group had more psychopathy on the IM-P, with anger, frustration, toughness and boundary violations and tended to more neuroticism on the BFI. When pre-TBI and post-TBI assessments were compared on the IAS and FrSBe, only the patients with blast force mTBI had become more cold-hearted, aloof–introverted and apathetic. Conclusion: These results suggest that blast forces alone can cause negativistic behavioural changes when evaluated with selected measures of personality. Further research on isolated blast-force mTBI should focus on these personality changes and their relationship to blast over-pressure.

Cognitive Performance after Lacunar Stroke Correlates with Leukoaraiosis Severity

Background: This study investigates the effect of leukoaraiosis on patients presenting with cognitive impairment after lacunar stroke. Methods: Fourty-six patients with cognitive impairment and newly discovered lacunar stroke detected by brain magnetic resonance imaging underwent neuropsychological testing. Results: Patients with both lacunar infarct and leukoaraiosis performed less well on cognitive measures, compared to those with lacunar infarcts alone. Additionally, leukoaraiosis severity inversely correlated with cognitive performance. Conclusions: In patients with lacunar stroke, presence of leukoaraiosis is associated with worse performance in multiple cognitive domains. These findings suggest lacunar infarcts plus leukoaraiosis is a common etiology for vascular dementia.

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 Alzheimers 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.

Frontal-executive Versus Posterior-perceptual Mental Status Deficits in Early-onset Dementias:

Background: Compared to late-onset dementias, early-onset dementias (EODs) may have greater focal cognitive involvement with differences in frontal-executive compared to posterior-perceptual deficits. Objective: This study evaluated whether mental status screening based on this frontal-posterior axis can distinguish EODs. Methods: Twenty-three patients each with early-onset Alzheimers disease (eAD), frontotemporal dementia (FTD), or subcortical ischemic vascular disease (SIVD), and 20 normal controls underwent the Frontal Assessment Battery (FAB) and the Perceptual Assessment Battery (PAB). Results: Compared to controls, SIVD and FTD groups were impaired on the FAB whereas eAD and SIVD groups were impaired on the PAB. The FAB/PAB ratio further differentiated the groups (F(3,85) = 26.49, P < .001). For sensitivities and specificities of 93%, a cut-off score of 1.25 on the FAB/PAB distinguished eAD, and a cut-off of 0.83 distinguishing FTD. Conclusion: Although preliminary, this study indicates that mental status screening based on frontal versus posterior cortical functions may help clinicians diagnose EODs.