MAPT Q336H mutation: Intrafamilial phenotypic heterogeneity in a new Italian family.

BACKGROUND AND PURPOSE: Q336H is a rare MAPT mutation, previously found in a single patient with behavioral variant frontotemporal dementia and tau pathology (Pick bodies). Here, we describe the clinical characteristics of two members of a new family carrying the Q336H MAPT mutation. METHODS: Clinical, genetic, and neuroradiological assessment and follow-up of the proband were made. RESULTS: At age 37 years, the proband developed naming and object recognition impairment, due to a lack of knowledge. After 3 years, he developed behavioral disorders. Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography showed the involvement of the left temporal pole. A diagnosis of semantic variant primary progressive aphasia (svPPA) was made. At follow-up after 6 and 12 months, a rapid worsening of cognitive deficits occurred. His parent presented, at age 65 years, slowly progressive memory deficits without behavioral impairment, and, on MRI, evidence of mesial temporal atrophy, consistent with a clinical diagnosis of Alzheimer disease (AD). CONCLUSIONS: This is the second family carrying the MAPT Q336H mutation reported so far. We showed that svPPA and AD-like phenotype can be associated with this mutation. A wide clinical variability exists at the intrafamilial level for Q336H MAPT mutation, pointing to genetic and/or environmental influencing factors on disease expression. We also confirmed that svPPA can be associated with MAPT mutations, suggesting that this gene should be analyzed also in patients with svPPA, especially with early onset. In addition, an AD-like phenotype may be associated with this mutation, suggesting its different effects on protein misfolding and aggregation.

On which abilities are category fluency and letter fluency grounded? A confirmatory factor analysis of 53 Alzheimer's dementia patients.

BACKGROUND/AIMS: In Alzheimer's dementia (AD), letter fluency is less impaired than category fluency. To check whether category fluency and letter fluency depend differently on semantics and attention, 53 mild AD patients were given animal and letter fluency tasks, two semantic tests (the Verbal Semantic Questionnaire and the BORB Association Match test), and two attentional tests (the Stroop Colour-Word Interference test and the Digit Cancellation test). METHODS: We conducted a LISREL confirmatory factor analysis to check the extent to which category fluency and letter fluency tasks were related to semantics and attention, viewed as latent variables. RESULTS: Both types of fluency tasks were related to the latent variable Semantics but not to the latent variable Attention. CONCLUSIONS: Our findings warn against interpreting the disproportionate impairment of AD patients on category and letter fluency as a contrast between semantics and attention.

Autobiographical memory in amnestic Mild Cognitive Impairment.

Autobiographical memory (ABM) was evaluated in 19 patients with amnestic Mild Cognitive Impairment (aMCI) by means of the standardized enquiry developed by Borrini et al. (Psychol Med 19:215-224, 1989). Longitudinal assessments were carried out by re-testing participants at 9-month intervals up to three assessments over 18 months. Although aMCI patients performed significantly worse than age-, gender- and education-matched normal controls, all of them achieved above normal scores according to Italian norms. No evidence of disproportionate sparing of remote memories (i.e., classical temporal gradient, TG) was found. These findings contrast with the previously reported significant impairment of memory for public events (Bizzozero et al. in J Clin Exp Neuropsychol 31:48-56, 2009). Such a discrepancy might be attributed to the adopted ABM enquiry tapping "personal semantics", presumed to rely largely on prefrontal functions, in contrast with the mainly episodic qualification of memory for past public events, which is mostly dependent on hippocampal structures. Our results also support the hypothesis that the contents of remote memory archives may be differentially affected in aMCI.

Mild cognitive impairment does entail retrograde amnesia for public events.

In this study memory for public events was evaluated in 15 amnesic mild cognitive impairment (aMCI) patients, whose clinical diagnosis was refined through a stringent selection procedure. A total of 9 patients were longitudinally reassessed over an 18-month period. About half of the participants were impaired at baseline and nearly 80% at the end of the 18-month follow-up. Moreover, retrograde memory declined significantly over time. Evidence of a pathological Ribot-type temporal gradient was found in about half of the aMCI patients. This is the first report of a remote memory deficit in aMCI. It highlights amnesia for public events as a frequent accompaniment of this condition. The findings tie in with the hypothesized role of the hippocampal complex in long-term memory.

Recollection of public events in healthy people: a latent-variable stochastic approach to disentangling retrieval and storage.

Recollection of media-mediated past events was examined in 96 healthy participants to investigate the interaction between the age of the subject and the "age" of memories. The results provided evidence that people older than 75 years recall recent events significantly worse than remote ones. Younger participants (47-60 years old) showed the reverse pattern. The implementation of a Markov chains latent-variable stochastic model suggested that reduced efficiency of retrieval rather than storage processes accounts for these results. The findings were interpreted with reference to models of memory trace consolidation, assuming that memory for past public events is dependent on hippocampal structures.