Despite numerous studies on the role of medial temporal lobe structures in Alzheimer's disease (AD), the magnitude and clinical significance of amygdala atrophy has been relatively sparsely investigated. In this study we compared the level of amygdala atrophy to that of the hippocampus in very mild and mild AD subjects in two large samples (Sample 1 n=90; Sample 2 n=174). Using a series of linear regression analyses, we investigated whether amygdala atrophy is related to global cognitive functioning (Clinical Dementia Rating Sum of Boxes: CDR-SB; Mini Mental State Examination: MMSE) and neuropsychiatric status. Results indicated that amygdala atrophy was comparable to hippocampal atrophy in both samples. MMSE and CDR-SB were strongly related to amygdala atrophy, with amygdala atrophy predicting MMSE scores as well as hippocampal atrophy, but predicting CDR-SB scores less robustly. Amygdala atrophy was related to aberrant motor behavior, with potential relationships to anxiety and irritability. These results suggest that the magnitude of amygdala atrophy is comparable to that of the hippocampus in the earliest clinical stages of AD, and is related to global illness severity. There also appear to be specific relationships between the level of amygdala atrophy and neuropsychiatric symptoms that deserve further investigation.

In this study, we validated a conversion table between MMSE and MoCA using a large multicenter sample. Our results suggest caution in interpreting the tables in heterogeneous clinical populations, as the MMSE-MoCA relationship may be different across dementia subtypes.

Recent studies have supported a role for amyloid positron emission tomography (PET) imaging in distinguishing Alzheimer's disease (AD) pathology from other pathological protein accumulations leading to dementia. We investigated the clinical utility of amyloid PET in the differential diagnosis of atypical dementia cases and its impact on caregivers. Using the amyloid tracer 18F-NAV4694, we prospectively scanned 28 patients (mean age 59.3 y, s.d. 5.8; mean MMSE 21.4, s.d. 6.0) with an atypical dementia syndrome. Following a comprehensive diagnostic workup (i.e., history taking, neurological examination, blood tests, neuropsychological evaluation, MRI, and FDG-PET), no certain diagnosis could be arrived at. Amyloid PET was then conducted and classified as positive or negative. Attending physicians were asked to evaluate whether this result led to a change in diagnosis or altered management. They also reported their degree of confidence in the diagnosis. Caregivers were met after disclosure of amyloid PET results and completed a questionnaire/interview to assess the impact of the scan. Our cohort was evenly divided between positive (14/28) and negative (14/28) 18F-NAV4694 cases. Amyloid PET resulted in a diagnostic change in 9/28 cases (32.1%: 17.8% changed from AD to non-AD, 14.3% from non-AD to AD). There was a 44% increase in diagnostic confidence. Altered management occurred in 71.4% (20/28) of cases. Knowledge of amyloid status improved caregivers' outcomes in all domains (anxiety, depression, disease perception, future anticipation, and quality of life). This study suggests a useful additive role for amyloid PET in atypical cases with an unclear diagnosis beyond the extensive workup of a tertiary memory clinic. Amyloid PET increased diagnostic confidence and led to clinically significant alterations in management. The information gained from that test was well received by caregivers and encouraged spending quality time with their loved ones.

. Clinical diagnoses in young offspring from eastern Que´bec multigenerational families densely affected by schizophrenia or bipolar disorder.Objective: The follow-up since 1989 of a large sample of multigenerational families of eastern Que´bec that are densely affected by schizophrenia (SZ) or bipolar disorder (BP) has permitted to look at the rates of DSM diagnoses in the young offspring of a SZ parent (HRSZ) and of a BP parent (HRBP) who had an extremely loaded family history. Method: The sample (average age of 17.5, SD 4.5) consisted of 54 highrisk offspring (HR) having one parent affected by a DSM-IV SZ or BP. The parents descended from 21 multigenerational families that constitute a quasi-total sample of such kindred in eastern Que´bec. The HRs were administered a lifetime best estimate DSM-IV diagnosis. Results: We observed that the rates, the diversity of diagnoses, the high comorbidity, the severity and the age of onset of the clinical diagnoses tended to be similar with those already reported in the offspring of affected parents with a low familial loading. Although the sample size was small, HRSZ and HRBP also tended to show similarities in their clinical status. Conclusion: Overall, taking into account methodological limitations, the observation early in life of some shared characteristics among HRSZ and HRBP in terms of non-psychotic diagnosis may be congruent with the accumulating evidence that several phenotypic features are shared in adulthood by the two major psychoses. Significant outcomes• Offspring at high genetic risk of major psychosis displayed early in life non-psychotic DSM disorders warranting a consultation.• Various and highly comorbid disorders were observable in these offspring at extreme genetic risk.• HRSZ and HRBP showed similarities in their clinical status. Limitations• Normal control group from the general population was absent.• Small sample size may have prevented detection of differences between HRSZ and HRBP.• Caution is required before generalizing findings to the offspring of an ill parent from the general population.Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

BackgroundForeign accent syndrome (FAS) is a rare speech disorder characterized by the appearance of a new accent, different from the speaker's native language and perceived as foreign by the speaker and the listener. In most of the reported cases, FAS follows stroke but has also been found following traumatic brain injury, cerebral haemorrhage and multiple sclerosis. In very few cases, FAS was reported in patients presenting with psychiatric disorders but the link between this condition and FAS was confirmed in only one case.Case presentationIn this report, we present the case of FG, a bipolar patient presenting with language disorders characterized by a foreign accent and agrammatism, initially categorized as being of psychogenic origin. The patient had an extensive neuropsychological and language evaluation as well as brain imaging exams. In addition to FAS and agrammatism, FG also showed a working memory deficit and executive dysfunction. Moreover, these clinical signs were related to altered cerebral activity on an FDG-PET scan that showed diffuse hypometabolism in the frontal, parietal and temporal lobes bilaterally as well as a focal deficit in the area of the anterior left temporal lobe. When compared to the MRI, these deficits were related to asymmetric atrophy, which was retrospectively seen in the left temporal and frontal opercular/insular region without a focal lesion.DiscussionTo our knowledge, FG is the first case of FAS imaged with an 18F-FDG-PET scan. The nature and type of neuropsychological and linguistic deficits, supported by neuroimaging data, exclude a neurotoxic or neurodegenerative origin for this patient's clinical manifestations. For similar reasons, a psychogenic etiology is also highly improbable.ConclusionTo account for the FAS and agrammatism in FG, various explanations have been ruled out. Because of the focal deficit seen on the brain imaging, involving the left insular and anterior temporal cortex, two brain regions frequently involved in aphasic syndrome but also in FAS, a cerebrovascular origin must be considered the best explanation to account for FG's language deficits.

These findings have implications for the conceptualization of aMCI, and foster investigation of social language comprehension in neurodegenerative diseases such as prodromal AD. Results are discussed in light of actual linguistic theories. The importance of evaluating the role of underlying cognitive processes in verbal irony comprehension is also emphasized.

Objective. The present study examined mentalizing capacities as well as the relative implication of mentalizing in the comprehension of ironic and sincere assertions among 30 older adults with mild cognitive impairment (MCI) and 30 healthy control (HC) subjects. Method. Subjects were administered a task evaluating mentalizing by means of short stories. A verbal irony comprehension task, in which participants had to identify ironic or sincere statements within short stories, was also administered; the design of the task allowed uniform implication of mentalizing across the conditions. Results. Findings indicated that participants with MCI have second-order mentalizing difficulties compared to HC subjects. Moreover, MCI participants were impaired compared to the HC group in identifying ironic or sincere stories, both requiring mental inference capacities. Conclusion. This study suggests that, in individuals with MCI, difficulties in the comprehension of ironic and sincere assertions are closely related to second-order mentalizing deficits. These findings support previous data suggesting a strong relationship between irony comprehension and mentalizing.

Background An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) is lacking. Objective In this study, we investigated the risk factors, anatomy, biology, and outcomes of NPS in AD. Methods 181 subjects were included from the Alzheimer’s Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI >3 was used as a threshold for NPS positivity. Three NPS courses were characterized: 1) minimal/absent (negative at 0 and 6 months, n = 77); 2) fluctuating (positive only at one time point, n = 53); 3) persistent (positive at both time points, n = 51). We examined the association between NPS course and family history of dementia, personal history of psychiatric disorders, cerebrospinal fluid biomarkers, atrophy patterns, as well as longitudinal cognitive and functional measures at 12 and 24 months (MMSE, CDR-SOB, FAQ). Results AD subjects with absent, fluctuating, or persistent NPS had similar CSF amyloid-β and tau levels. AD subjects with minimal/absent NPS had less personal history of psychiatric disorders (35%) than those with fluctuating (57%; p = 0.015) or persistent NPS (47%, not significant). At 24 months, AD subjects with persistent NPS had worse cognitive (MMSE; p = 0.05) and functional (CDR-SOB; p = 0.016) outcomes. Dorsolateral prefrontal atrophy was seen in persistent NPS, but not in fluctuating NPS. Conclusions Our results suggest that individuals with personal history of psychiatric disorders might be more vulnerable to develop NPS throughout the course of AD. The worst cognitive and functional outcomes associated with NPS in AD underscores the importance of monitoring NPS early in the disease course.