Characterization of the initial complaint and care pathways prior to diagnosis in very young sporadic Alzheimer's disease.

BACKGROUND: Very-early-onset Alzheimer's disease (young-AD) differentiates from late-onset AD (old-AD) by a predominant involvement of the parietal neocortex leading to atypical presentations. The diagnosis of AD is often not the first to be mentioned in such young patients. METHODS: We retrospectively reviewed the initial complaint and care pathways of 66 sporadic young-AD (age < 62) and 30 old-AD patients (age > 65) and compared their neuropsychological profiles at the time of diagnosis (based on clinical-biological criteria) with 44 amyloid-negative controls. RESULTS: The initial complaint of young-AD was non-cognitive and mimicked a burnout in 32% of cases. Their main cognitive complaints were memory (38% vs 87% in old-AD) and language (17% vs 13%) impairment. The referral to a psychiatrist prior to AD diagnosis was more frequent in young-AD than in old-AD (26% vs 0%). At the time of diagnosis, young-AD were at a more severe stage of dementia than old-AD (24% vs 10% with CDR ≥ 1) but had less anosognosia. CONCLUSIONS: Better identifying the initial signs of very-early-onset AD is crucial to improve the early diagnosis and develop new treatments.

Executive and social-cognitive determinants of environmental dependency syndrome in behavioral frontotemporal dementia.

OBJECTIVE: Environmental dependency syndrome (EDS), including utilization (UB) and imitation (IB) behaviors, is often reported in behavioral variant frontotemporal dementia (bvFTD). These behaviors are commonly attributed to executive dysfunction. However, inconsistent associations between EDS and poor executive performance has led to an alternative "social hypothesis," instead implicating patients' misinterpretation of the examiner's intention. We investigated the possible explanatory cognitive mechanisms of EDS in bvFTD by relating UB and IB to performance on tests of executive functioning and theory of mind (ToM). METHOD: This study analyzed retrospective data of 32 bvFTD patients. Data included scores of UB and IB, various executive measures, and ToM assessment using the faux pas test, from which we extracted a mental attribution score. RESULTS: Of the patients, 15.6% and 40.6% exhibited UB and IB, respectively. We conducted an automatic linear modeling analysis with executive and mental attribution measures as predictor variables, and UB and IB sequentially considered as target variables. ToM mental attribution score, visual abstraction and flexibility measures from the Wisconsin Card Sorting Test, and motor sequence performance significantly (corrected ps < .05) predicted IB. No executive or ToM measures significantly predicted UB. CONCLUSIONS: These findings reveal a complex interaction between executive dysfunction and mental attribution deficits influencing the prevalence of EDS in bvFTD. Further investigation is required to improve our understanding of the mechanisms underlying these behaviors. (PsycINFO Database Record

Effortless control: executive attention and conscious feeling of mental effort are dissociable.

Recruitment of executive attention is normally associated to a subjective feeling of mental effort. Here we investigate the nature of this coupling in a patient with a left mesio-frontal cortex lesion including the anterior cingulate cortex (ACC), and in a group of comparison subjects using a Stroop paradigm. We show that in normal subjects, subjective increases in effort associated with executive control correlate with higher skin-conductance responses (SCRs). However, our patient experienced no conscious feeling of mental effort and showed no SCR, in spite of exhibiting normal executive control, and residual right anterior cingulate activity measured with event-related potentials (ERPs). Finally, this patient demonstrated a pattern of impaired behavior and SCRs in the Iowa gambling task-elaborated by Damasio, Bechara and colleagues-replicating the findings reported by these authors for other patients with mesio-frontal lesions. Taken together, these results call for a theoretical refinement by revealing a decoupling between conscious cognitive control and consciously reportable feelings. Moreover, they reveal a fundamental distinction, observed here within the same patient, between the cognitive operations which are depending on normal somatic marker processing, and those which are withstanding to impairments of this system.

Subtle cognitive impairment but no dementia in patients with spastin mutations.

BACKGROUND: The most frequent form of autosomal dominant hereditary spastic paraparesis is associated with the SPG4 locus, described originally as a pure form of the disease. Mutations of the SPG4 gene have been increasingly associated with reports of cognitive impairment. OBJECTIVE: To investigate cognitive function in 10 families with hereditary spastic paraparesis due to mutations in the SPG4 gene, using intrafamilial control subjects. PATIENTS AND METHODS: Neuropsychological examinations, including the Cambridge Cognitive Evaluation, were conducted in 29 carriers with identified SPG4 mutations and 29 intrafamilial controls. RESULTS: Carriers were not demented but had a subclinical cognitive impairment primarily affecting executive functions. The dysfunction was more severe in those carriers older than 50 years, but was correlated with the progression of the disease, not with age. Disease progression and cognitive impairment appeared to be more severe in the carriers of missense mutations than in those with truncating mutations. CONCLUSION: Asymptomatic cognitive impairment mostly affecting executive functions is present in SPG4 mutation carriers and is more frequent in those with missense mutations.