Littérature scientifique sur le sujet « AD non amnesico »

ABSTRACT Besides its typical amnesic presentation, focal atypical presentations of Alzheimer's disease (AD) have been described in neuropathological studies. These phenotypical variants of AD (so-called "atypical AD") do not follow the typical amnestic pattern and include non-amnestic focal cortical syndromes, such as posterior cortical atrophy and frontal variant AD. These variants exhibit characteristic histological lesions of Alzheimer pathology at post-mortem exam. By using physiopathological markers, such as cerebrospinal fluid markers, it is now possible to establish in vivo a biological diagnosis of AD in these focal cortical syndromes. We report a series of eight patients who were diagnosed with behavioural variant frontotemporal dementia based on their clinical, neuropsychological and neuroimaging findings, while CSF biomarkers showed an AD biological profile, thus supporting a diagnosis of frontal variant of AD.

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

Memory encoding and retrieval deficits have been identified in atypical Alzheimer’s disease (AD), including posterior cortical atrophy (PCA) and logopenic variant primary progressive aphasia (lvPPA), despite these groups being referred to as “non-amnestic”. There is a critical need to better understand recognition memory in atypical AD. We investigated performance on the California Verbal Learning Test (CVLT-II-SF) in 23 amyloid-positive, tau-positive, and neurodegeneration-positive participants with atypical “non-amnestic” variants of AD (14 PCA, 9 lvPPA) and 14 amnestic AD participants. Recognition memory performance was poor across AD subgroups but trended toward worse in the amnestic group. Encoding was related to recognition memory in non-amnestic but not in amnestic AD. We also observed cortical atrophy in dissociable subregions of the distributed memory network related to encoding (left middle temporal and angular gyri, posterior cingulate and precuneus) compared to recognition memory (anterior medial temporal cortex). We conclude that recognition memory is not spared in all patients with atypical variants of AD traditionally thought to be “non-amnestic”. The non-amnestic AD patients with poor recognition memory were those who struggled to encode the material during the learning trials. In contrast, the amnestic AD group had poor recognition memory regardless of encoding ability.

Background: Hypometabolism of the posterior cingulate cortex (PCC) is an important diagnostic feature of late-onset, amnestic Alzheimer’s disease (AD) measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, it is unclear whether PCC hypometabolism has diagnostic value in young-onset, non-amnestic variants of AD, which exhibit less pathology in the hippocampus and default mode network. Objective: Evaluate the prevalence and diagnostic value of PCC hypometabolism in non-amnestic variants of AD. Methods: We retrospectively identified 60 patients with young-onset, atypical dementia who have undergone a detailed clinical evaluation, FDG-PET, and an amyloid biomarker (amyloid-PET or cerebrospinal fluid analysis). We quantitatively analyzed regional hypometabolism in 70 regions of interest (ROI) using the MIMneuro® software. Results: Based on a cut-off of z-score < –1.5 for significant PCC hypometabolism, the prevalence of PCC hypometabolism in non-amnestic variants of AD was 65% compared to 28% in clinical variants of frontotemporal dementia (FTD). The ROI with the maximal hypometabolism was the dominant middle temporal gyrus in the language variant of AD (mean z score –2.28), middle occipital gyrus in PCA (–3.24), middle temporal gyrus in frontal AD (–2.70), and angular gyrus in corticobasal syndrome due to AD (–2.31). The PCC was not among the 10 most discriminant regions between non-amnestic variants of AD versus clinical variants of FTD. Conclusion: We conclude that PCC hypometabolism is not a discriminant feature to distinguish non-amnestic variants of AD from clinical variants of FTD—and should be interpreted with caution in patients with young-onset, non-amnestic dementia.

SYNOPSISThe memory deficit in Alzheimer's disease (AD) has been characterized as consisting of multiple components. The purpose of this study was to confirm the utility of a two-process model, and to examine changes in the nature and extent of the neuropsychological deficits after a one-year interval. The results replicate the initial observation that the memory loss in AD can be described as consisting of a focal amnesic syndrome and a dysexecutive syndrome characterized by failure of rapid information processing and search of both episodic and semantic memory. One year after the initial observation, all dysexecutive patients and the majority of the amnesic patients had become non-focal. No patient developed a dysexecutive syndrome, but 18 patients developed amnesic syndromes. These results suggest that, like other aspects of the cognitive deficits of AD, the memory loss is multifactorial. These results have implications for understanding the pathophysiology of AD, and for designing pharmacotherapeutic intervention.

Background/Aims: Mild cognitive impairment (MCI) is a frequent syndrome in the older population, which involves an increased risk to develop Alzheimer's disease (AD). The latter can be modified by the cognitive reserve, which can be operationalized by the length of school education. MCI can be differentiated into four subtypes according to the cognitive domains involved: amnestic MCI, multiple-domain amnestic MCI, non-amnestic MCI and multiple-domain non-amnestic MCI. While neurocognitive deficits are a constituent of the diagnosis of these subtypes, the question of how they refer to the cognitive reserve still needs to be clarified. Methods: We examined neuropsychological deficits in healthy controls, patients with MCI and patients with mild AD (n = 485) derived from a memory clinic. To reduce the number of neuropsychological variables, a factor analysis with varimax rotation was calculated. In a second step, diagnostic groups including MCI subtypes were compared with respect to their clinical and neuropsychological characteristics including cognitive reserve. Results: Most MCI patients showed the amnestic multiple-domain subtype followed by the pure amnestic subtype, while the non-amnestic subtypes were rare. The amnestic subtype displayed a significantly higher level of cognitive reserve and higher MMSE scores than the amnestic multiple-domain subtype, which was in most cases characterized by additional psychomotor and executive deficits. Conclusions: These findings confirm earlier reports revealing that the amnestic multiple-domain subtype is the most frequent one and indicating that a high cognitive reserve may primarily prevent psychomotor and executive deficits in MCI.

ABSTRACTBackground: Clinical subtypes of mild cognitive impairment (MCI) were assigned as potential prodromes to various types of dementia. Amnestic MCI (aMCI) is said to have a high likelihood of progressing to Alzheimer's dementia (AD) and non-amnestic MCI (naMCI) subtypes are assumed to have a higher likelihood of progressing to non-AD dementia. The aim of this study was to investigate the prognostic accuracy of aMCI and naMCI for the development of AD, vascular dementia (VaD), and mixed dementia.Methods: In this longitudinal study, 487 subjects without dementia (cognitively healthy: n = 387; MCI cases: n = 115) aged 75 years at baseline, who participated in a population-based cohort study (Vienna Transdanube Aging study), were available for analysis. The observation period was 90 months. The diagnoses of the clinical MCI subtypes were made according to common criteria. The outcome (AD, VaD, mixed dementia) was described for both MCI subtypes. Diagnostic values of aMCI and naMCI according to incident AD, VaD, and mixed dementia were determined.Results: AD was the most common type of dementia following both MCI subtypes. Participants with aMCI were more likely to progress to AD than participants with naMCI. The proportion of incident VaD and mixed dementia did not differ concerning the MCI subtypes. The positive predictive value for both MCI subtypes was low (range: 1%–46%), whereas the negative predictive value was high (range: 86%–99%).Conclusions: The increased risk of clinical MCI subtypes for a particular type of dementia could only be confirmed for aMCI and incident AD.

Abstract Objective: LATE is a common but underrecognized neuropathology that causes a progressive amnestic syndrome in older adults which mimics an Alzheimer’s disease (AD) clinical profile. Method: A 75-year-old female with a history of progressive cognitive impairment presented to a multidisciplinary neurology clinic. Neurocognitive screening during her neurological exam showed an amnestic memory profile. A work-up for medical causes for her cognitive impairment was negative. She had prominent hippocampal atrophy on MRI with a negative amyloid PET scan, raising concerns for LATE. She was referred for a comprehensive neuropsychological evaluation. Results: Neuropsychological testing confirmed an amnestic mild dementia profile in the context of her other cognitive skills (e.g., attention, executive functioning, processing speed, word finding, and visuospatial abilities) being largely preserved. On self-report questionnaires, the patient denied having any significant symptoms of depression or anxiety. Conclusions: LATE is described as causing a primarily amnestic neurocognitive profile with associated hippocampal atrophy and this was well demonstrated in our patient. While the diagnosis of LATE cannot be definitively made until autopsy, the absence of amyloid on her PET scan highly suggests a non-AD pathology like LATE. A limitation of the evaluation is that tau biomarker tests were not performed, making primary age-related tauopathy (PART) another possible pathology or co-pathology. Overall, this case study illustrates the importance of multidisciplinary assessment to help facilitate differential diagnosis for neurodegenerative conditions associated with amnestic cognitive impairment, especially when a non-AD pathology is suspected.

Objective:Aim of the present review study was to describe and compare the neurocognitive features of MCI which could predict its progression to DLB vs AD.Background:Progression of MCI to AD or DLB is a relatively recent field of study with emphasis on the clinical or neuropsychological features of MCI which could potentially predict its progression to specific types of dementia.Methods:A literature review in the Pubmed database has been made, after the year 2005, using the key- words: neuropsychological assessment; MCI; AD; DLB; progression to dementia. Seventeen relevant articles have been found.Results:Data from most studies supports that, in MCI, impairment in executive, attentional and visuospatial functions, as well as letter fluency and fluctuating concentration are mainly related to progression to DLB. In contrast, prominent episodic and recognition memory deficits are mostly found in MCI which progresses in AD. Furthermore, non-amnestic MCI has been related most often to progression in DLB, whereas the amnestic type to AD, although memory loss may not necessarily predict the development of AD. Nevertheless, fewer studies suggest that MCI-DLB is related to cognitive profile similar to that of MCI-AD, while cognitive scoring alone does not accurately predict MCI-DLB vs MCI-AD. Interestingly, quantitative electroencephalogram has been found to help in predicting the progression of MCI to DLB, while preservation of hippocampal volume is associated with increased risk of DLB vs AD, especially in non-amnestic MCI. Moreover, specific patterns on neuroimaging MCI may predict progression to AD in contrast to DLB.Conclusions:Predicting the progression of MCI to AD or DLB based on neuropsychological profiles is challenging and useful for early therapeutic interventions. More studies are needed, since there are some conflicting findings and, at present, the combination of clinical symptoms with neurocognitive assessment and neuroimaging is the ideal method for the prediction of MCI progression to various types of dementia.

AbstractObjectivesIndividuals with essential tremor (ET) exhibit a range of cognitive deficits generally conceptualized as “dysexecutive” or “fronto-subcortical,” and thought to reflect disrupted cortico-cerebellar networks. In light of emerging evidence that ET increases risk for Alzheimer’s disease (AD), it is critical to more closely examine the nature of specific cognitive deficits in ET, with particular attention to amnestic deficits that may signal early AD.MethodsWe performed a cross-sectional analysis of baseline data from 128 ET cases (age 80.4±9.5 years) enrolled in a longitudinal, clinical-pathological study. Cases underwent a comprehensive battery of motor-free neuropsychological tests and a functional assessment to inform clinical diagnoses of normal cognition (ET-NC), mild cognitive impairment (MCI) (ET-MCI), or dementia (ET-D). ET-MCI was subdivided into subtypes including: amnestic single-domain (a-MCI), amnestic multi-domain (a-MCI+), non-amnestic single-domain (na-MCI), or non-amnestic multi-domain (na-MCI+).ResultsNinety-one (71.1%) cases were ET-NC, 24 (18.8%) were ET-MCI, and 13 (10.2%) were ET-D. Within MCI, the a-MCI+ subtype was the most common (13/24; 54.2%) followed by a-MCI (4/24; 16.7%), na-MCI+ (4/24; 16.7%), and na-MCI (3/24; 12.5%). Cases with amnestic MCI demonstrated lower recognition memoryZ-scores (−2.4±1.7) than non-amnestic groups (−0.9±1.2) (p=.042).ConclusionsAmnestic MCI, defined by impaired memory recall but associated with lower memory storage scores, was the most frequent MCI subtype in our study. Such impairment has not been explicitly discussed in the context of ET and may be an early hallmark of AD. Results have implications for the prognosis of specific cognitive deficits in ET. (JINS, 2017,23, 390–399)

Recenti studi sulla progressione della malattia d’Alzheimer(AD)suggeriscono che la patologia possa essere trasmessa da un’area all’altra del cervello tramite diffusione locale o lungo le fibre assonali.Tuttavia,quest’ipotesi necessita di maggiori conferme ed è ancora meno chiaro se questi modelli possano essere applicabili alle varianti non amnesiche di AD(naAD),un gruppo di fenotipi AD caratterizzati da relativo risparmio all’esordio della memoria episodica e deficit cognitivi dominio-specifici.Pochi studi ad oggi hanno infatti analizzato la progressione longitudinale della malattia in naAD, tutti al massimo con due sole di queste varianti. Inizialmente abbiamo confrontato 240 RMN pesate in T1 da 129 pazienti AD con RMN di controlli sani per stabilire l’atrofia in 120 regioni di interesse(ROI); poi abbiamo calcolato modelli di progressione di malattia separatamente per ogni fenotipo: AD amnesici(aAD),variante logopenica di afasia primaria progressiva(lvPPA),atrofia corticale posteriore(PCA)e variante frontale di AD(fvAD).Tutti i pazienti avevano evidenza di patologia AD tramite dati autoptici o da liquor cefalorachidiano(CSF).I risultati dalla coorte di aAD sono stati utilizzati per determinare i parametri per l’algoritmo di assegnazione delle fasi,basato sull’associazione con lo staging di patologia di Braak. Per ogni variante AD,4 fasi di atrofia regionale sono state definite sulla base della frequenza decrescente di atrofia tra i soggetti.Abbiamo osservato pattern unici di atrofia cumulativa per ogni fenotipo.Le ROI di fase 1 nel nostro modello rappresentano l’origine anatomica di ogni fenotipo,inclusi: il lobo temporale mesiale(MTL)per il gruppo aAD(risparmiato negli altri gruppi),il lobo temporale sinistro nella lvPPA,la corteccia parieto-occipitale nella PCA,quella temporo-parietale per la CBS e le aree fronto-temporali per la fvAD.Successivamente abbiamo assegnato una fase ad ogni RMN dei pazienti in base alla somiglianza dei pattern di atrofia regionale con l’atrofia predetta per il fenotipo corrispondente ad ogni fase.Le fasi ROI erano correlate con parametri patologici disponibili,mentre le fasi RMN erano correlate con misure demografiche e cliniche. Dopodiché abbiamo deciso di studiare le modifiche nel tempo della sostanza grigia(GM)in una coorte di pazienti in parte sovrapposta a quella usata per lo studio trasversale,ad esclusione di CBS: 17 aAD,25 lvPPA,20 PCA e 12 fvAD,con 37 controlli abbinati.Abbiamo analizzato il volume della GM e le sue modifiche longitudinali nelle ROI di fase 1 dallo studio trasversale per naAD e l’MTL per aAD.Abbiamo anche studiato l’atrofia longitudinale al di fuori di queste aree tramite un’analisi accessoria all’intero cervello e abbiamo comparato i fenotipi tra loro. Abbiamo osservato pattern regionali unici di atrofia iniziale e diffusione longitudinale nella neocorteccia con tassi differenti in lvPPA,PCA e fvAD,che correlavano con i deficit cognitivi.La progressione di atrofia nel tempo ha coinvolto aree sia prossimali sia distanti dal sito d’esordio della malattia,suggerendo quindi più meccanismi di diffusione della patologia coinvolti; per quanto riguarda il secondo,in particolare,una misura di connettività strutturale prediceva la severità di atrofia longitudinale,corroborando quindi l’ipotesi delle vie lunghe.Nell’MTL,i pazienti naAD mostravano al basale meno atrofia dei pazienti aAD,ma i tassi longitudinali non erano diversi tra gruppi; il relativo risparmio dell’MTL in naAD potrebbe quindi essere dovuto a un esordio più tardivo della degenerazione nell’MTL rispetto all’aAD,considerando che l’età più avanzata era associata con atrofia in quest’area,indipendentemente dal gruppo. Il presente studio ha corroborato probabili aree di malattia precoce in naAD e mostrato che ogni fenotipo ha un diverso pattern di progressione di atrofia lungo la corteccia,fornendo anche dati importanti sulla trasmissione della patologia.
Recent studies of Alzheimer’s disease (AD) spread suggest that pathology may be transmitted from one brain area to another either via local diffusion or long-way transport via white matter pathways. However, this hypothesis requires more confirmations, and it’s even more unclear whether such models are applicable in non-amnestic AD (naAD), a group of AD phenotypes characterized by relative spared episodic memory at onset and domain-specific cognitive impairments. Few studies to date have in fact addressed the longitudinal spread of disease in naAD, and all of them considering no more than two variants. At first we compared 240 T1-weighted anatomical MRIs from 129 AD patients with elderly controls’ scans to assess atrophy in each of 120 regions-of-interest (ROIs); then we computed disease progression models separately for each phenotype: typical amnestic AD (aAD), logopenic variant primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), corticobasal syndrome (CBS), and frontal-variant AD (fvAD). All patients had autopsy or cerebrospinal fluid (CSF) evidence of AD pathology. Results from the amnestic cohort were used to determine appropriate parameters for the phase assignment algorithm, based on association with Braak pathology staging. For each AD variant, 4 phases of regional atrophy were defined based on decreasing frequency of atrophy across participants. We observed a unique distribution of accumulating atrophy for each phenotype. Phase 1 ROIs in our model represent the anatomical origin for each phenotype, including: medial temporal lobe (MTL) for the aAD group (spared in the other phenotypes), left lateral temporal lobe for lvPPA, occipito-parietal cortex for PCA, temporo-parietal cortex for CBS, and fronto-temporal cortex for fvAD. We subsequently assigned a phase to each patient MRI scan based on the similarity of regional atrophy patterns with atrophy predicted for the corresponding phenotype at each phase. ROI phases were strongly correlated with available pathological factors, while MRI phase was significantly correlated with demographic and clinical measures. Then we decided to investigate grey matter (GM) change over time in MRIs within a cohort of patients partly overlapping with the sample used for the cross-sectional study, with the exception of CBS patients (insufficient longitudinal data): 17 aAD, 25 lvPPA, 20 PCA, and 12 fvAD patients, compared to 37 matched controls. We analyzed GM volume and its longitudinal change in phase 1 ROIs from the cross-sectional study for naAD variants, and in MTL for aAD. We also investigated longitudinal atrophy outside these areas through an accessory whole-brain analysis, and we compared phenotypes between each other. We observed unique regional patterns of initial atrophy and longitudinal neocortical disease spread with different rates in lvPPA, PCA, and fvAD, which correlated with cognitive impairments. Atrophy spread over time included both proximal and distant regions from the hypothesized focus of disease onset, thus suggesting that multiple mechanisms of disease progression may have been involved; for what concerns the second mechanism, in particular, a measurement of structural connectivity predicted the severity of longitudinal atrophy, thus corroborating the hypothesis of long-distance fiber pathways. In MTL regions, naAD patients had less severe atrophy than aAD patients at baseline, but longitudinal rates did not differ between groups; MTL sparing in naAD may be due to later onset of MTL degeneration than in aAD, considering that older age was associated with atrophy in this area, independent of group. The current study corroborated probable areas of early disease for naAD and showed that each phenotype has a different pattern of atrophy progression across the cortex, providing also important data about pathology transmission.

Background: amnestic Mild Cognitive Impairment (aMCI) refers to a possibletransitional stage between healthy aging and dementia and has an increased chance of converting to Alzheimer’s disease (AD). Objectives: to assess whether neuropsychological tests can predict the conversion to AD in patients with aMCI and altered CSF amyloid peptide (βA+). Methods: 48 individuals underwent neuropsychological assessment (time 0 and time 1), being 18 healthy controls and 30 aMCI βA+, who performed a single CSF collection (time 0). All subjects with aMCI scored 0.5 in the Memory category of the Clinical Dementia Rating (CDR) test, and we considered the conversion to AD if the overall score changed from 0.5 to 1. We performed different additional univariate analyses with MANOVAs to differentiate between groups. Results : 8 subjects converted to AD (converters), and 22 remained stable (non-converters). The converters performed worse in the sub-item test Recognition of Rey Auditory Verbal Learning Test (RAVLT) compared to controls and non-converters (F = 14,58, p <0,001). Conclusions: the Recognition task of the RAVLT was able to differentiate aMCI βA+ individuals who converted to AD in our sample, which was not observed in the other investigated tests. We suggest additional studies with larger sample sizes and validation cohorts to contribute to our findings.

Background: MCI can be classified as amnestic (aMCI) or non-amnestic (naMCI). Patients with aMCI are at increased risk of developing Alzheimer’s disease (AD). The clinical diagnosis encompasses episodic memory decline with preservation of activities of daily living, in addition to possible changes in other cognitive domains. Nevertheless, there is a lack of studies in the Brazilian population comparing the performance of aMCI on different episodic memory tests. Objectives: This study investigated episodic memory alterations in patients with aMCI and healthy controls (HC) through population-validated tests. Methods: We included 54 individuals, 36 aMCI and 18 HC. The neuropsychological protocol included estimated total IQ [vocabulary and matrix reasoning], Logical Memory (LM), Visual Reproduction (VR) and Rey Auditory Verbal Learning Test (RAVLT). Results: Significant differences were found between the groups in LM delayed recall (p=0.048); Visual Memory immediate recall (p=0.002); Visual Memory delayed recall (p=0.006); RAVLT immediate recall (p=0.19); RAVLT delayed recall (p=0.006) and RAVLT recognition (p=0.001). Conclusions: aMCI patients showed significant cognitive deficits in all episodic memory tests, except for the LM immediate recall. These findings corroborate the international literature and indicate the possibility of identifying differential cognitive alterations in the MCI.