Utility of the Repeat and Point Test for Subtyping Patients With Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA). OBJECTIVE: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA. METHOD: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture. Data from 204 patients (68 svPPA, 85 nfvPPA, and 51 lvPPA) and 33 healthy controls were analyzed. RESULTS: Controls completed both tasks with >90% accuracy. Patients with svPPA had high scores in repetition (mean=9.2±1.32) but low scores in pointing (mean=6±2.52). In contrast, patients with nfvPPA and lvPPA performed comparably in both tasks with lower scores in repetition (mean=7.4±2.7 for nfvPPA and 8.2±2.34 for lvPPA) but higher scores in pointing (mean=8.9±1.41 for nfvPPA and 8.6±1.62 for lvPPA). The R&P Test had high accuracy discriminating svPPA from nfvPPA (83% accuracy) and lvPPA (79% accuracy). However, there was low accuracy discriminating nfvPPA from lvPPA (<60%). CONCLUSION: The R&P Test helps to differentiate svPPA from 2 nonsemantic variants (nfvPPA and lvPPA). However, additional tests are required for the differentiation of nfvPPA and lvPPA.

Dissociation of amyloid biomarkers in PET and CSF in Alzheimer's disease: a case report.

BACKGROUND: Recently, biomarkers have been suggested to be incorporated into diagnostic criteria for Alzheimer's disease (AD). Regarding disease-specific brain amyloid-beta deposition these comprise low amyloid-beta 1-42 in cerebrospinal fluid (CSF) and positive positron emission tomography (PET) amyloid imaging, while neuronal degeneration is evidenced by high total and phosphorylated tau levels in CSF (t-/p-tau), regional hypometabolism ([(18)F]fluorodeoxyglucose PET, FDG-PET) and characteristic atrophy-patterns (magnetic resonance imaging, MRI). CASE PRESENTATION: Here we present a case of clinically and biomarker supported AD (CSF t-/p-tau, MRI, FDG-PET) in a 59-year-old Caucasian man in whom indicators of amyloid-beta deposition dissociated between CSF parameters and the respective PET imaging. CONCLUSIONS: Such cases highlight the necessity to better understand potential dissociations between PET and CSF data for amyloid-beta biomarkers, because they are currently considered interchangeably valid with regard to in-vivo evidence for AD pathology. This is more important since amyloid deposition markers can be considered a very first prognostic indicator of imminent AD, prior to neurodegenerative biomarkers and cognitive symptoms. The case illustrates the need for further longitudinal data on potential dissociations of AD biomarkers to devise recommendations for their better prognostic and diagnostic interpretation in the future.

Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration - a pilot FDG-PET study.

Behavioral and executive dysfunctions are typical symptoms of frontotemporal lobar degeneration, associated with its subtypes frontotemporal and semantic dementia. Although both functions depend on the frontal lobes, no study has yet compared their neural correlates in frontotemporal lobar degeneration. Accordingly, we correlated clinical scores of behavioral and executive deficits with glucose utilization as measured by [(18)F]fluorodeoxyglucose positron emission tomography in 17 patients with frontotemporal lobar degeneration and 9 age- and sex-matched control subjects. Impairment in executive functions was measured by the Behavioral Assessment of the Dysexecutive Syndrome, a modified Stroop paradigm and/or the Tower of Toronto Test. Behavioral deficits were examined with the Neuropsychiatric Inventory. Executive dysfunction was correlated with diminished glucose utilization in frontomedial and frontolateral cortices. Brain regions included the anterior cingulate and midcingulate gyri, anterior medial frontal cortex, and left frontolateral cortex. Behavioral deficits were associated with mainly frontomedial networks, particularly the anterior medial frontal cortex, gyrus rectus, and area subcallosa. Our pilot study reveals partially overlapping neural correlates of executive and behavioral dysfunction in frontotemporal lobar degeneration. The results suggest that some behavioral deficits, namely disinhibition and appetite and eating abnormalities, are particularly related to executive dysfunction. This hypothesis might be further explored in studies involving larger patient groups.

Citalopram Improves Obsessive-Compulsive Crossword Puzzling in Frontotemporal Dementia.

Behavioral variant frontotemporal dementia (bvFTD) is characterized by severe changes in personality/behavior. Recent studies have provided evidence that a decrease in serotonin receptors and neuronal loss in the raphe nuclei play a role in the bvFTD pathology. Serotonergic antidepressants have been reported to diminish behavioral disturbances in bvFTD, particularly repetitive behaviors, disinhibition, apathy, sexually inappropriate behaviors, and hyperorality. Here, we present the case of an 80-year-old Caucasian male patient with clinically and biomarker supported bvFTD ("probable" bvFTD; disease-specific alterations in 18F-fluorodesoxyglucose positron emission tomography and magnetic resonance imaging). The patient exhibited behavioral disinhibition, apathy, a loss of empathy, perseverative behavior during testing, hyperorality, changes in diet, and executive deficits in neuropsychological testing. Remarkably, he failed in solving crosswords by systematically filling in the blanks by letters in alphabetical order (A, B, C, D, etc.), indicating obsessive-compulsive behavior. One year later, the patient visited the clinic again for a follow-up investigation. He had taken 20 mg of citalopram per day for 1 consecutive year. Remarkably, he had regained the ability to fill in crossword puzzles correctly, although the neuropsychiatric inventory showed overall only small improvement in behavioral impairment. A regimen of 20 mg citalopram per day over the course of 1 year led to a specific improvement in one of the bvFTD core symptoms, obsessive-compulsive behavior, most pronounced in solving crossword puzzles. This case contributes to the understanding of the neuropharmacological correlates of bvFTD and supports the treatment of bvFTD's behavioral symptoms with selective serotonin reuptake inhibitors.

Lesion-site affects grammatical gender assignment in German: perception and production data.

Two experiments investigated phonological, derivational-morphological and semantic aspects of grammatical gender assignment in a perception and a production task in German aphasic patients and age-matched controls. The agreement of a gender indicating adjective (feminine, masculine or neuter) and a noun was evaluated during perception in Experiment 1 (grammaticality judgment). In Experiment 2 the same participants had to produce the matching definite article to a noun. In the perception task patients with left frontal lesions (LF) made more errors during phonological gender assignment as compared to derivational-morphological and semantic gender assignment, while patients with lesions of the posterior superior temporal gyrus (pSTG) made more errors in derivational-morphological gender assignment as compared to phonological and semantic gender assignment. In the production task no differences between patient groups were found. These data support previous evidence that left frontal brain areas are critically involved in phonological processing. The pSTG on the other hand may be critically engaged in the integration of phonological and lexical information essential for phonological and derivational-morphological gender assignment.

Identifying neural correlates of memory and language disturbances in herpes simplex encephalitis: a voxel-based morphometry (VBM) study.

Herpes simplex encephalitis (HSE) is a severe neurological disease that often leads to persistent cognitive deficits in survivors. Memory and naming impairments have been reported most, although direct association between memory and naming performance and disease-related atrophy has not yet been demonstrated in vivo for a larger sample of patients. In the present work, a voxel-based morphometry (VBM) analysis was conducted on 3T magnetic resonance imaging (MRI) of 13 HSE survivors. The gray matter density values were correlated with scores indicating verbal memory decline, as well as errors/omissions in picture naming; both were obtained through neuropsychological assessment. Analysis of individual lesion patterns revealed a considerable inter-individual variability, mainly with atrophy in the basal forebrain, adjacent frontal cortex, medial and lateral temporal cortex, insula and thalamus. The neuropsychological data analysis revealed correlation between verbal memory decline and atrophy especially in the left hippocampal region, whereas naming problems were associated with gray matter loss especially in the lateral temporal lobe, the thalamus and the left insula. These results confirm, for the first time, the assumptions of earlier studies about the considerable variability of individual lesion patterns in HSE in a whole-brain approach in vivo, and thus the anatomical validity of VBM.