This study examined the time course of object naming in 21 individuals with primary progressive aphasia (PPA) (8 agrammatic (PPA-G); 13 logopenic (PPA-G)) and healthy age-matched speakers (n=17) using a semantic interference paradigm with related and unrelated interfering stimuli presented at stimulus onset asynchronies (SOAs) of −1000, −500, −100 and 0 ms. Results showed semantic interference (SI) (i.e. significantly slower RTs in related compared to unrelated conditions) for all groups at −500, −100 and 0 ms, indicating timely spreading activation to semantic competitors. However, both PPA groups showed a greater magnitude of SI than normal across SOAs. The PPA-L group and six PPA-G participants also evinced SI at −1000 ms, suggesting an abnormal time course of semantic interference resolution, and concomitant left hemisphere cortical atrophy in brain regions associated with semantic processing. These subtle semantic mapping impairments in non-semantic variants of PPA may contribute to the anomia of these patients.

Background

Classical aphasiology, based on the study of stroke sequelae, fuses speech fluency and grammatical ability. Nonfluent (Broca's) aphasia often is accompanied by agrammatism; whereas in the fluent aphasias grammatical deficits are not typical. The assumption that a similar relationship exists in primary progressive aphasia (PPA) has led to the dichotomization of this syndrome into fluent and nonfluent subtypes.

Aims

This study compared elements of fluency and grammatical production in the narrative speech of individuals with PPA to determine if they can be dissociated from one another.

Method

Speech samples from 37 individuals with PPA, clinically assigned to agrammatic (N=11), logopenic (N=20) and semantic (N=6) subtypes, and 13 cognitively healthy control participants telling the “Cinderella Story” were analyzed for fluency (i.e., words per minute (WPM) and mean length of utterance in words (MLU-W)) and grammaticality (i.e., the proportion of grammatically correct sentences, open-to-closed-class word ratio, noun-to-verb ratio, and correct production of verb inflection, noun morphology, and verb argument structure.) Between group differences were analyzed for each variable. Correlational analyses examined the relation between WPM and each grammatical variable, and an off-line measure of sentence production.

Outcomes And Results

Agrammatic and logopenic groups both had lower scores on the fluency measures and produced significantly fewer grammatical sentences than did semantic and control groups. However, only the agrammatic group evinced significantly impaired production of verb inflection and verb argument structure. In addition, some semantic participants showed abnormal open-to-closed and noun-to-verb ratios in narrative speech. When the sample was divided on the basis of fluency, all the agrammatic participants fell in the nonfluent category. The logopenic participants varied in fluency but those with low fluency showed variable performance on measures of grammaticality. Correlational analyses and scatter plots comparing fluency and each grammatical variable revealed dissociations within PPA participants, with some nonfluent participants showing normal grammatical skill.

Conclusions

Grammatical production is a complex construct comprised of correct usage of several language components, each of which can be selectively affected by disease. This study demonstrates that individuals with PPA show dissociations between fluency and grammatical production in narrative speech. Grammatical ability, and its relationship to fluency, varies from individual to individual, and from one variant of PPA to another, and can even be found in individuals with semantic PPA in whom a fluent aphasia is usually thought to accompany preserved ability to produce grammatical utterances.

This study provides empirical evidence on whether polypharmacy and potentially inappropriate prescription medications (PIRx, as defined by the 2003 Beers criteria) increase the likelihood of functional decline among community-dwelling older adults with dementia. Data were from the National Alzheimer’s Coordinating Center, Uniform Data Set (9/2005–9/2009). Study sample included 1994 community-dwelling participants aged ≥65 with dementia at baseline. Results showed that participants having ≥5 medications were more likely to have functional decline than participants having <5 medications. However, the increased likelihood was only apparent in participants who did not have PIRx. Instead of magnifying the associated risk as hypothesized, PIRx appeared to have a protective effect albeit marginally statistically significant. Therefore, increased medication burden may be associated with functional decline in community-dwelling older adults with dementia who are not prescribed with PIRx. More research is needed to understand which classes of medications have the most deleterious effect on this population.

Whereas patients with Alzheimer's disease (AD) experience difficulties forming and retrieving memories, their memory impairments may also partially reflect an unrecognized dysfunction in sleep-dependent consolidation that normally stabilizes declarative memory storage across cortical areas. Patients with amnestic mild cognitive impairment (aMCI) exhibit circumscribed declarative memory deficits, and many eventually progress to an AD diagnosis. Whether sleep is disrupted in aMCI and whether sleep disruptions contribute to memory impairment is unknown. We measured sleep physiology and memory for two nights and found that aMCI patients had fewer stage-2 spindles than age-matched healthy adults. Furthermore, aMCI patients spent less time in slow-wave sleep and showed lower delta and theta power during sleep compared to controls. Slow-wave and theta activity during sleep appear to reflect important aspects of memory processing, as evening-to-morning change in declarative memory correlated with delta and theta power during intervening sleep in both groups. These results suggest that sleep changes in aMCI patients contribute to memory impairments by interfering with sleep-dependent memory consolidation.

The value of self-reported memory complaints for identifying or predicting future cognitive decline or dementia is controversial, but observations from a third party, or “informant”, may prove more useful. The relationship between Informant and Self ratings of cognitive status and neuropsychological test scores was examined in a cohort of 384 non-demented, community-dwelling women, aged sixty and older, participating in a single-site Women’s Health Initiative ancillary study. Each participant and her respective informant separately completed the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)1. Participants also underwent neuropsychological testing and responded to questionnaires on depression and functioning in complex activities of daily living. All neuropsychological test scores were significantly correlated (p-values <.05 to <.01) with Informant IQCODE ratings while Self ratings overestimated cognitive functioning in some domains. Furthermore, the Self and Informant ratings were both positively correlated with depression and negatively correlated with participants’ activity level. Therefore, Informant judgments of functional abilities are robust predictors of cognitive status in high functioning non-demented women. These results suggest that informants may be sensitive to changes that are not clinically significant but that may represent an incipient trend for decline.

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

The goal of this study was to determine if the apolipoprotein ε (ApoE) gene, which is a well-established susceptibility factor for Alzheimer’s disease (AD) pathology in typical amnestic dementias, may also represent a risk factor in the language-based dementia, primary progressive aphasia (PPA). Apolipoprotein E genotyping was obtained from 149 patients with a clinical diagnosis of PPA, 330 cognitively healthy individuals (NC) and 179 patients with a clinical diagnosis of probable Alzheimer’s disease (PrAD). Allele frequencies were compared among the groups. Analyses were also completed by gender and in two subsets of PPA patients, one where patients were classified by subtype (logopenic, agrammatic and semantic) and another where pathologic data were available. The allele frequencies for the PPA group (ε2:5%, ε3:79.5%, and ε4:15.4%) showed a distribution similar to the NC group but significantly different from the PrAD group. The presence of an ε4 allele did not influence the age of symptom onset or aid in the prediction of AD pathology in PPA. These data show that the ε4 polymorphism, which is a well-known risk factor for AD pathology in typical amnestic dementias, has no similar relationship to the clinical syndrome of PPA or its association with AD pathology.

Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from “normal,” age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.

Alzheimer disease (AD) targets neuroanatomical networks for episodic memory before those for language, executive functions, and visuospatial abilities. Therefore, amnestic dementia is strongly associated with early AD pathology.

The National Institute on Aging and the Alzheimer’s Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer’s disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Bio-marker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca’s area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions.

Sleep is important for declarative memory consolidation in healthy adults. Sleep disruptions are typical in Alzheimer’s disease, but whether they contribute to memory impairment is unknown. Sleep has not been formally examined in amnestic mild cognitive impairment (aMCI), which is characterized by declarative-memory deficits without dementia and can signify prodromal Alzheimer’s disease. We studied 10 aMCI patients and 10 controls over 2 weeks using daily sleep surveys, wrist-worn activity sensors, and daily recognition tests. Recognition was impaired and more variable in aMCI patients, whereas sleep was similar across groups. However, lower recognition of items learned the previous day was associated with lower subjective sleep quality in aMCI patients. This correlation was not present for information learned the same day, thus did not reflect nonspecific effects of poor sleep on memory. These results indicate that inadequate memory consolidation in aMCI patients is related to declines in subjective sleep indices. Furthermore, participants with greater across-night sleep variability exhibited lower scores on a standardized recall test taken prior to the 2-week protocol, suggesting that consistent sleep across nights also contributes to successful memory. Physiological analyses are needed to further specify which aspects of sleep in neurological disorders impact memory function and consolidation.

Introduction

With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z-score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets.

Methods

Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model.

Results

For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output.

Conclusions

An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease.

While normal aging is associated with a marked decline in cognitive abilities, such as memory and executive functions, recent evidence suggests that control processes involved in regulating responses to emotional stimuli may remain well-preserved in the elderly. However, neither the precise nature of these preserved control processes, nor their domain-specificity with respect to comparable non-emotional control processes, are currently well-established. Here, we tested the hypothesis of domain-specific preservation of emotional control in the elderly by employing two closely matched behavioral tasks that assessed the ability to shield the processing of task-relevant stimulus information from competition by task-irrelevant distracter stimuli that could be either non-emotional or emotional in nature. The efficacy of non-emotional versus emotional task-set shielding, gauged via the ‘conflict adaptation effect’, was compared between cohorts of healthy young adults, healthy elderly adults, and individuals diagnosed with probable Alzheimer’s disease (PRAD), age-matched to the elderly subjects. It was found that, compared to the young adult cohort, the healthy elderly displayed deficits in task-set shielding in the non-emotional but not in the emotional task, whereas PRAD subjects displayed impaired performance in both tasks. These results provide new evidence that healthy aging is associated with a domain-specific preservation of emotional control functions, specifically, the shielding of a current task-set from interference by emotional distracter stimuli. This selective preservation of function supports the notion of partly dissociable affective control mechanisms, and may either reflect different time-courses of degeneration in the neuroanatomical circuits mediating task-set maintenance in the face of non-emotional versus emotional distracters, or a motivational shift towards affective processing in the elderly.

Dementia of the Alzheimer’s type (DAT) is a major public health threat in developed countries where longevity has been extended to the eighth decade of life. Estimates of prevalence and incidence ofDAT vary with what is measured, be it change from a baseline cognitive state or a clinical diagnostic endpoint, such as Alzheimer’s disease. Judgment of what is psychometrically “normal” at the age of 80 years implicitly condones a decline from what is normal at the age of 30. However, because cognitive aging is very heterogeneous, it is reasonable to ask “Is ‘normal for age’ good enough to screen forDAT or its earlier precursors of cognitive impairment?” Cost containment and accessibility of ascertainment methods are enhanced by well-validated and reliable methods such as screening for cognitive impairment by telephone interviews. However, focused assessment of episodic memory, the key symptom associated with DAT, might be more effective at distinguishing normal from abnormal cognitive aging trajectories. Alternatively, the futuristic “Smart Home,” outfitted with unobtrusive sensors and data storage devices, permits the moment-to-moment recording of activities so that changes that constitute risk for DAT can be identified before the emergence of symptoms.

This cross-sectional study examines the association between total prescription medication use and potentially inappropriate medication use (PIRx) among community-dwelling elderly patients with and without dementia. Data (9/2005-9/2007) were from the NIA-funded National Alzheimer's Coordinating Center Uniform Data Set (UDS). The study analyzed the UDS initial visits of 4,518 community-dwelling subjects aged 65+ with and without dementia (2,665 and 1,853, respectively). PIRx was defined using a partial list of the 2003 Beers criteria. Generalized linear mixed models were applied to estimate the association between PIRx and polypharmacy. In both groups (with and without dementia), subjects who received PIRx on average took more medications than those taking no PIRx. As the total number of medications used increased, the odds of having PIRx also increased, controlling for dementia diagnosis and other subject characteristics. Our key findings were consistent after considering two definitions of PIRx (with or without oral estrogens) and accounting for missing data. In summary, the total number of medications used is associated with PIRx among ADC's community-dwelling elderly patients with and without dementia, with polypharmacy increasing the risk of PIRx. Ensuring appropriate medication use in this population is clinically important because of the significant risks for institutionalization.

Primary progressive aphasia (PPA), a selective neurodegeneration of the language network, frequently causes object naming impairments. We examined the N400 event-related potential (ERP) to explore interactions between object recognition and word processing in 20 PPA patients and 15 controls. Participants viewed photographs of objects, each followed by a word that was either a match to the object, a semantically related mismatch, or an unrelated mismatch. Patients judged whether word– object pairs matched with high accuracy (94% PPA group; 98% control group), but they failed to exhibit the normal N400 category effect (N400c), defined as a larger N400 to unrelated versus related mismatch words. In contrast, the N400 mismatch effect (N400m), defined as a larger N400 to mismatch than match words, was observed in both groups. N400m magnitude was positively correlated with neuropsychological measures of word comprehension but not fluency or grammatical competence, and therefore reflected the semantic component of naming. After ERP testing, patients were asked to name the same set of objects aloud. Trials with objects that could not be named were found to lack an N400m, although the name had been correctly recognized at the matching stage. Even accurate overt naming did not necessarily imply normal semantic processing, as shown by the absent N400c. The N400m was preserved in one patient with postsemantic anomia, who could write the names of objects she could not verbalize. N400 analyses can thus help dissect the multiple cognitive mechanisms that contribute to object naming failures in PPA.

Objective

To provide a quantitative algorithm for classifying primary progressive aphasia (PPA) into agrammatic (PPA-G), semantic (PPA-S) and logopenic (PPA-L) variants, each of which is known to have a different probability of association with Alzheimer’s disease (AD) versus frontotemporal lobar degeneration (FTLD).

Design

Prospectively and consecutively enrolled 16 PPA patients tested with neuropsychological instruments and magnetic resonance imaging (MRI).

Setting

University medical center.

Participants

PPA patients recruited nationally in the USA as part of a longitudinal study.

Results

A two-dimensional template, reflecting performance on tests of syntax (Northwestern Anagram Test) and lexical semantics (Peabody Picture Vocabulary Test), classified all 16 patients in concordance with a clinical diagnosis that had been made prior to the administration of the quantitative tests. All three subtypes had distinctly asymmetrical atrophy of the left perisylvian language network. Each subtype also had distinctive peak atrophy sites. Only PPA-G had peak atrophy in the IFG (Broca’s area), only PPA-S had peak atrophy in the anterior temporal lobe, and only PPA-L had peak atrophy in area 37.

Conclusions

Once an accurate root diagnosis of PPA is made, subtyping can be quantitatively guided using a two-dimensional template based on orthogonal tasks of grammatical competence and word comprehension. Although the choice of tasks and precise cut-off levels may evolve in time, this set of 16 patients demonstrates the feasibility of using a simple algorithm for clinico-anatomical classification in PPA. Prospective studies will show whether this suptyping can improve the clinical prediction of underlying neuropathology.

Pathogenic mutations in the gene encoding TDP-43, TARDBP, have been reported in familial amyotrophic lateral sclerosis (FALS) and, more recently, in families with a heterogeneous clinical phenotype including both ALS and frontotemporal lobar degeneration (FTLD). In our previous study, sequencing analyses identified one variant in the 3′-untranslated region (3′-UTR) of the TARDBP gene in two affected members of one family with bvFTD and ALS and in one unrelated clinically assessed case of FALS. Since that study, brain tissue has become available and provides autopsy confirmation of FTLD-TDP in the proband and ALS in the brother of the bvFTD-ALS family and the neuropathology of those two cases is reported here. The 3′-UTR variant was not found in 982 control subjects (1,964 alleles). To determine the functional significance of this variant, we undertook quantitative gene expression analysis. Allele-specific amplification showed a significant increase of 22% (P < 0.05) in disease-specific allele expression with a twofold increase in total TARDBP mRNA. The segregation of this variant in a family with clinical bvFTD and ALS adds to the spectrum of clinical phenotypes previously associated with TARDBP variants. In summary, TARDBP variants may result in clinically and neuropathologically heterogeneous phenotypes linked by a common molecular pathology called TDP-43 proteinopathy.

In the present study, we have correlated plasma TDP-43 levels, as measured by ELISA, with the presence of TDP-43 pathological changes in the brains of 28 patients with frontotemporal lobar degeneration (FTLD) (14 with FTLD-TDP and 14 with FTLD-tau) and 24 patients with pathologically confirmed AD (8 with, and 16 without, TDP-43 pathological changes). Western blotting revealed full-length TDP-43, including a phosphorylated form, and a phosphorylated C-terminal fragment, in all samples examined. Both ELISA and immunohistochemistry were performed using phospho-dependent and phospho-independent TDP-43 antibodies for detection of phosphorylated and total TDP-43, respectively. Over all 52 cases, plasma levels of TDP-43, and scores of brain TDP-43 pathology, determined using TDP-43 phospho-dependent antibody correlated with the equivalent measure determined using the TDP phospho-independent antibody. In FTLD, but not AD, TDP-43 plasma levels correlated significantly with the pathology score when using the TDP-43 phospho-dependent antibody, but a similar correlation was not seen in either FTLD or AD using the TDP-43 phospho-independent antibody. With the TDP-43 phospho-independent antibody, there were no significant differences in median plasma TDP-43 levels between FTLD, or AD, patients with or without TDP-43 pathology. Using TDP-43 phospho-dependent antibody, median plasma TDP-43 levels were greater in patients with, than in those without, TDP-43 pathology for FTLD patients, though not significantly so, but not for AD patients. Present assays for TDP-43 do not differentiate between FTLD, or AD, patients with or without TDP-43 pathological changes in their brains. However, the levels of phosphorylated TDP-43 in plasma do correlate with the extent of TDP-43 brain pathology in FTLD, and therefore might be a useful surrogate marker for tracking changes in TDP-43 brain pathology during the course of this disease.

Researchers from Alzheimer’s Disease Centers (ADCs) across the United States with expertise in the assessment of Spanish-speaking elderly collaborated to create the official Spanish version of measures in the Uniform Data Set of the National Institute on Aging Alzheimer’s Disease Center Program. The present article describes this project, whose primary goal was to create Spanish instruments with cultural and linguistic equivalence to the English versions. The resulting Spanish versions make provisions for variations among Spanish-speaking groups in the United States of different nationalities, socio-cultural, linguistic, and educational backgrounds. A consensus-based translation and adaptation approach was used, and guiding principles and specific components of this process are summarized. The Spanish translation and adaptation of the Uniform Data Set measures became available online to ADCs in April 2007. Its creation is important, as the resulting effort provides standardized measures for the collection of cross-sectional and longitudinal data on a large cohort of Spanish-speaking elders across the country and facilitates collaborative research among ADCs.

Behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) are related dementias with different presenting symptoms, but with increasing symptom-overlap as they progress. Loss of insight is associated with early bvFTD, but not PPA. This study used the Frontal Behavioral Inventory (FBI) to compare patient and caregiver concepts of symptom presence and severity. BvFTD patients were found to have worse insight overall than PPA patients. However, the PPA group showed reduced insight into behavioral symptoms, and the bvFTD groups had intact insight into some language symptoms. Theoretical and clinical implications are discussed.

The semantic variant of primary progressive aphasia (PPA) is characterized by the combination of word comprehension deficits, fluent aphasia and a particularly severe anomia. In this study, two novel tasks were used to explore the factors contributing to the anomia. The single most common factor was a blurring of distinctions among members of a semantic category, leading to errors of overgeneralization in word–object matching tasks as well as in word definitions and object descriptions. This factor was more pronounced for natural kinds than artifacts. In patients with the more severe anomias, conceptual maps were more extensively disrupted so that inter-category distinctions were as impaired as intra-category distinctions. Many objects that could not be named aloud could be matched to the correct word in patients with mild but not severe anomia, reflecting a gradual intensification of the semantic factor as the naming disorder becomes more severe. Accurate object descriptions were more frequent than accurate word definitions and all patients experienced prominent word comprehension deficits that interfered with everyday activities but no consequential impairment of object usage or face recognition. Magnetic resonance imaging revealed three characteristics: greater atrophy of the left hemisphere; atrophy of anterior components of the perisylvian language network in the superior and middle temporal gyri; and atrophy of anterior components of the face and object recognition network in the inferior and medial temporal lobes. The left sided asymmetry and perisylvian extension of the atrophy explains the more profound impairment of word than object usage and provides the anatomical basis for distinguishing the semantic variant of primary progressive aphasia from the partially overlapping group of patients that fulfil the widely accepted diagnostic criteria for semantic dementia.

The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain–behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinicoanatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies.