Beauty and Paintings: Aesthetic Experience in Patients with Behavioral Variant Frontotemporal Dementia When Viewing Abstract and Concrete Paintings.

We assessed the aesthetic experience of patients with behavioral variant frontotemporal dementia (bvFTD) to understand their ability to experience feelings of the sublime and to be moved when viewing paintings. We exposed patients with bvFTD and control participants to concrete and abstract paintings and asked them how moved they were by these paintings and whether the latter were beautiful or ugly. Patients with bvFTD declared being less moved than control participants by both abstract and concrete paintings. No significant differences were observed between abstract and concrete paintings in both patients with bvFTD and control participants. Patients with bvFTD provided fewer "beautiful" and more "ugly" responses than controls for both abstract and concrete paintings. No significant differences in terms of "beautiful" and "ugly" responses were observed between abstract and concrete paintings in both patients with bvFTD and control participants. These findings suggest disturbances in the basic affective experience of patients with bvFTD when they are exposed to paintings, as well as a bias in their ability to judge the aesthetic quality of paintings.

Increased Pupil Size during Future Thinking in a Subject with Retrograde Amnesia.

Recent research has assessed pupil size during past thinking in patients with retrograde amnesia. Building on this research, we assessed pupil size during future thinking in a retrograde amnesia patient. To this end, we measured pupil size during past and future thinking in L, a 19-year-old, right-handed man free of neurological/psychiatric disorders except for retrograde amnesia that occurred after an episode of fugue. During a past thinking condition, we invited L to retrieve retrograde events (i.e., events that occurred before amnesia) and anterograde events (i.e., events that occurred after amnesia). During a future thinking condition, we invited him to imagine events that might occur the following week, the following month, and in the new year. Past and future thinking occurred while L's pupil size was monitored with eye-tracking glasses. L demonstrated higher specificity during future than during past thinking. Critically, the results demonstrated a larger pupil size during future than during past thinking. The larger pupil size during future thinking observed in L can be attributed to the high cognitive load involved in future thinking. Our study not only demonstrates preserved future thinking in a patient with dissociative retrograde amnesia, but also shows that pupillometry can be used for the physiological assessment of future thinking in retrograde amnesia patients.

Amnesia in your pupils: decreased pupil size during autobiographical retrieval in a case of retrograde amnesia.

We investigate whether retrograde-amnesia can be indexed with pupil activity. We present the case of L, 19-year-old, without neurological or psychiatric disorders except for retrograde-amnesia. We invited L to retrieve retrograde and anterograde memories while his pupil size was monitering with eye-tracking glasses. Results demonstrated impaired retrograde retrieval but successful anterograde retrieval in L. He also attributed lower emotional value and visual imagery to his retrograde compared to his anterograde memories. Critically, smaller pupils were observed during retrograde than during anterograde retrieval. Our study provides the first evidence on the value of pupillometry as a potential physiological marker of amnesia.

The Effects of Confinement on Neuropsychiatric Symptoms in Alzheimer's Disease During the COVID-19 Crisis.

BACKGROUND: Neuropsychiatric symptoms, such as depression, anxiety, apathy, agitation, and hallucinations, are frequent in Alzheimer's disease (AD) and their prevalence tends to increase with external stressors. OBJECTIVE: We offer the first investigation of the effects of confinement during the COVID-19 crisis on neuropsychiatric symptoms in patients with AD. METHODS: We contacted caregivers of 38 patients with AD who were confined to their homes for nearly two months and asked them to report whether patients experienced any change in neuropsychiatric symptoms during, compared to before, the confinement and rate its severity and impact on themselves using the Neuropsychiatric Inventory-Questionnaire. RESULTS: Among the 38 patients, only 10 demonstrated neuropsychiatric changes during the confinement. Cognitive function of these 10 patients, assessed with the Mini-Mental State Examination, was worse than that of patients who did not demonstrate neuropsychiatric changes. Interestingly, among the 10 patients with neuropsychiatric changes, the duration of confinement significantly correlated with the severity of symptoms as well as with their caregivers' distress. DISCUSSION: The confinement seems to impact neuropsychiatric symptomatology in AD patients with low baseline cognitive function.

Impact of Confinement on the Burden of Caregivers of Patients with the Behavioral Variant of Frontotemporal Dementia and Alzheimer Disease during the COVID-19 Crisis in France.

INTRODUCTION: The clinical presentation of the behavioral variant of frontotemporal dementia (bvFTD) differs from that of Alzheimer disease (AD), with major impairments in behavioral functions in bvFTD and cognitive impairment in AD. Both behavioral disturbances in bvFTD and cognitive impairment in AD contribute to caregiver burden. OBJECTIVE: To investigate the impact of home confinement during the COVID-19 crisis on the burden of caregivers of bvFTD or AD patients. METHODS: During the COVID-19 lockdown in France, neurologists and neuropsychologists from the Memory Center of Nantes Hospital conducted teleconsultations for 38 AD patients and 38 bvFTD patients as well as for their caregivers. During these consultations, caregivers were invited to rate the change in their burden during home confinement. They were also invited to rate behavioral or emotional changes in the patients during, compared with before, the confinement. RESULTS: Twenty-two bvFTD caregivers and 14 AD caregivers experienced an increase in burden. For bvFTD caregivers, this increased burden occurred regardless of behavioral changes, while AD caregivers experienced an increased burden related to changes in patients' neuropsychiatric symptoms. Among the whole cohort, 2 factors were associated with increased caregiver burden: behavioral change and bvFTD. CONCLUSION: The results demonstrate that during home confinement in the COVID-19 crisis, neuropsychiatric symptoms were the core factor that impacted caregiver burden in different ways depending on the disease.

Randomized placebo-controlled trial of sodium valproate in progressive supranuclear palsy.

OBJECTIVES: Results from preclinical studies suggest that inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for tauopathies. The aim of the present study was therefore to determine the effects of sodium valproate (VPA), a GSK-3 inhibitor, on disease progression in progressive supranuclear palsy (PSP). PATIENTS AND METHODS: We performed a double-blind, randomized, placebo-controlled trial, in 28 PSP patients who received VPA (1500mg/day) or matching placebo for 24 months. The primary endpoint was the change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at 12 and 24 months. Secondary endpoints evaluated the effects of VPA on cognitive and behavioral status (MMSE, Mattis Dementia Rating Scale, Wisconsin Card Sorting, Gröber and Buschke and Oral Denomination 80 tests), tolerability of treatment, and patient compliance. RESULTS: There were no baseline differences between active treatment and placebo groups in age and clinical rating scores. PSPRS score at 12 months was significantly higher in the VPA than in the placebo group (60.8±20 versus 46.9±18.6 respectively, p=0.01), but was similar between the two groups at 24 months. No significant differences were observed between VPA and placebo groups for the secondary endpoints. CONCLUSION: Our results suggest that VPA is not effective as a disease-modifying agent in PSP.

A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation.

SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations.

Value of neuropsychological testing, imaging, and CSF biomarkers for the differential diagnosis and prognosis of clinically ambiguous dementia.

The objective of this study was to examine the diagnostic accuracy of imaging and CSF biomarkers in clinically ambiguous dementia (CAD). 69 patients were prospectively followed. The endpoint was clinical diagnosis at follow-up of 24 months based upon existing criteria. Medial temporal lobe atrophy score on MRI, distinctive patterns on 99 mTc-HMPAO-SPECT, and CSF levels of amyloid-ß peptide, total tau protein, and P-tau181P were used together with neuropsychological testing to assess Se (sensitivity) and Sp (specificity) of separate and combined markers. 60 patients reached the endpoint. A definite diagnosis was achieved in 48 patients. CSF biomarkers had a Sp of 71% and a Se of 100% for Alzheimer's disease (AD) diagnosis. Sp increased to 88% and 93% when MRI and MRI + SPECT were combined, at the expense of Se. CSF biomarkers levels also provided clues to frontotemporal (FTD) or vascular dementias (VaD) diagnosis when situated in an intermediate range between normal and pathological values. MRI and SPECT contributed mostly to the diagnosis of VaD (Se 88%, Sp 75%) and FTD (Se 73%, Sp 78%), respectively. Initial neuropsychological testing had a poor diagnostic accuracy, except for a neuropsychiatric inventory score >40 for the diagnosis of FTD (Se 73%, Sp 84%). Independent of the clinical diagnosis, medial temporal lobe atrophy and total-tau were best correlated with cognitive decline at 2 years. In conclusion, CSF biomarkers efficiently predict evolution toward an AD phenotype in CAD. Imaging biomarkers mostly contribute to the differential diagnosis between non-AD dementias. Initial neuropsychological testing was poorly contributive in CAD diagnosis.

Zarit burden inventory and activities of daily living in the behavioral variant of frontotemporal dementia.

BACKGROUND: Activities of daily living (ADL) and caregiver burden are known to have a major impact on the decision to institutionalize patients with Alzheimer's disease (AD), yet little research has been done on these aspects in patients with frontotemporal dementia (FTD). AIM: To compare ADL and caregiver burden in FTD and in early-onset AD. METHODS: We compared 26 FTD and 28 AD patients with respect to the Neuropsychiatric Inventory (NPI), Mini Mental State Examination, Mattis Dementia Rating Scale (MDRS), Disability Assessment for Dementia (DAD) and Zarit Burden Inventory (ZBI). RESULTS: Demographic variables for FTD and AD were similar. FTD patients obtained a significantly higher NPI behavioral score than AD patients (median, 39.5 vs. 11; p < 0.0001). However, the two groups did not differ in their total DAD score. No correlations were observed between DAD and cognitive status (MDRS) or between DAD and behavioral impairment (NPI). The ZBI was higher in FTD than in AD patients (median, 40 vs. 18.5; p = 0.0004) and was correlated with the NPI in both groups. CONCLUSION: Functional disability was similar in FTD and AD patients. Nevertheless, the caregiver burden was higher in FTD than in AD, a result that has important implications for caregiver help.