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.
Lesion studies indicate that the lateral and inferior temporal cortex is a critical area of semantic memory storage, but little is known about the cortical organization of semantics within this area. One proposition has been that dominant physical characteristics of objects (structure, motility) are determining factors. A positron emission tomography experiment using the H2(15)O bolus method was performed to test this hypothesis by contrasting activation for concrete and abstract concepts. Unlike previous studies that considered this question, the task required explicit word meaning judgments, and blocks of trials were designed to be of equal difficulty for the two word classes. The task required elderly participants to read aloud the pair of words that was closer in meaning (e.g., spade-shovel vs. spade-carpet). Subtraction analyses that compared the semantic judgment tasks with a baseline condition indicated that both abstract and concrete concepts activated the left lateral temporal cortex. A direct comparison of abstract versus concrete scans indicated differences in the lateralization of fusiform activation. We conclude that although concreteness might be a critical factor in the fusiform cortex, it is not dominant in the lateral temporal cortex. A multistudy overview suggests that tasks that focus on one concept per trial activate areas posterior to y = -40, whereas those that invoke several concepts, as in the present study, activate areas anterior to this. Increased processing complexity may proceed in a posterior-anterior direction in the lateral temporal cortex.
Semantic deficits have been documented in the prodromal phase of Alzheimer's disease, but it is unclear whether these deficits are associated with non-cognitive manifestations. For instance, recent evidence indicates that cognitive deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated by concomitant depressive symptoms. The purposes of this study were to (i) investigate if semantic memory impairment in aMCI is modulated according to the presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii) compare semantic memory performance of aMCI and aMCI-D groups to that of patients with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26 healthy control participants were administered a semantic questionnaire assessing famous person knowledge. Results showed that performance of aMCI-D patients was impaired compared to the control and LLD groups. However, in the aMCI group performance was comparable to that of all other groups. Overall, these findings suggest that semantic deficits in aMCI are somewhat associated with the presence of concomitant depressive symptoms. However, depression alone cannot account solely for the semantic deficits since LLD patients showed no semantic memory impairment in this study. Future studies should aim at clarifying the association between depression and semantic deficits in older adults meeting aMCI criteria. (JINS, 2011, 17, 865-874)
Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance.
This retrospective study examined the role of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis of atypical/unclear dementias in a memory clinic setting. A total of 94 patients with a diagnosis of mild cognitive impairment (MCI) or dementia, who had a PET study within 2 months of their diagnosis, were reevaluated at 5 and 18 months. Results showed that PET was associated with a change in diagnosis in 29% of patients and a 64% increase in the use of cholinesterase inhibitors (ChEIs). PET significantly lowered the number of atypical/unclear diagnoses from 39.4% to 16% and nearly 30% of these were found to have a typical Alzheimer's disease (AD) pattern of hypometabolism. In conclusion, the addition of PET to the investigation of atypical/unclear cases of dementia helped generating a more accurate diagnosis and initiating earlier treatment. PET was of limited contribution to typical AD and frontotemporal dementia (FTD) cases. This study provides guiding evidence about the true value of PET imaging in the day-to-day challenge of dementia diagnosis.
Introduction The Consortium for the early identification of Alzheimer's disease–Quebec (CIMA‐Q) created a research infrastructure to recruit, characterize, and track disease progression in individuals at risk of dementia. Methods CIMA‐Q established standardized clinical, neuropsychological, neuroimaging, blood (plasma, serum, RNA, genomic DNA), cryopreserved peripheral blood mononuclear cells, and cerebrospinal fluid collection protocols. These data and biological materials are available to the research community. Results In phase 1, 115 persons with subjective cognitive decline, 88 with mild cognitive impairment, 31 with early probable Alzheimer's disease, and 56 older adults with no worries nor impairments received detailed clinical and cognitive evaluations as well as blood and peripheral blood mononuclear cells collections. Among them, 142 underwent magnetic resonance imaging, 29 a 18fluorodeoxyglucose positron emission tomography, and 60 a lumbar puncture. Discussion CIMA‐Q provides procedures and resources to identify early biomarkers and novel therapeutic targets, and holds promise for detecting cognitive decline in Alzheimer's disease.
Introduction: Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic. Methods: We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aβ1–42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient’s diagnosis and management. Results: The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP. Interpretation: Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.
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