Non-memory subjective cognitive concerns predict incident motoric cognitive risk syndrome.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is a predementia condition that combines slow gait and subjective cognitive concerns. As the earliest markers of MCR are relatively unknown, the role of subjective cognitive concerns was investigated to predict incident MCR in a well-characterized prospective cohort of non-demented older adults. METHODS: Non-demented MCR-free older adults (n = 476) from the Central Control of Mobility in Aging cohort completed gait, subjective cognition and neuropsychological assessment at baseline and follow-up. Subjective concerns were analyzed via responses to 12 items from three validated measures, the Late-Life Function and Disability Instrument - Disability Component, the Activities of Daily Living Prevention Instrument and the Geriatric Depression Scale, and were independent of items utilized to diagnose MCR. Cox proportional hazard models examined the association between cognitive concerns and incident MCR. RESULTS: After 2.36 ± 1.4 years, 28 participants developed MCR. Executive functioning (adjusted hazard ratio 2.458, 95% confidence interval 1.094-5.524, P = 0.029) and mental clarity concerns (adjusted hazard ratio 3.917, 95% confidence interval 1.690-9.077, P = 0.001) were associated with incident MCR, controlling for age, sex, education and gait speed. CONCLUSIONS: Subjective cognitive concerns in non-memory cognitive domains predict incident MCR. Although most MCR studies assess cognitive concerns about memory, our findings suggest the need to broaden the scope of subjective cognitive assessment to enhance the accuracy of diagnosis and prediction of future cognitive decline.

World Trade Center exposure, post-traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers.

OBJECTIVE: To determine whether World Trade Center (WTC)-exposure intensity and post-traumatic stress disorder (PTSD) are associated with subjective cognitive change in rescue/recovery workers. METHOD: The population included 7875 rescue/recovery workers who completed a subjective cognition measure, the Cognitive Function Instrument (CFI), between 3/1/2018 and 2/28/2019 during routine monitoring, indicating whether they had experienced cognitive and functional difficulties in the past year. Higher scores indicated greater self-perceived cognitive change. Probable PTSD, depression, and alcohol abuse were evaluated by validated mental health screeners. Logistic regression assessed the associations of WTC exposure and current PTSD with top-quartile (≥2) CFI score, and of early post-9/11 PTSD with top-quartile CFI in a subpopulation (N = 6440). Models included demographics, smoking, depression, and alcohol abuse as covariates. RESULTS: Mean age at CFI completion was 56.7 ± 7.7 (range: 36-81). Participants with high-intensity WTC exposure had an increased likelihood of top-quartile CFI score (odds ratio[OR] vs. low exposure: 1.32, 95%CI: 1.07-1.64), controlling for covariates. Current and early PTSD were both associated with top-quartile CFI (OR: 3.25, 95%CI: 2.53-4.19 and OR: 1.56, 95%CI: 1.26-1.93) respectively. CONCLUSIONS: High-intensity WTC exposure was associated with self-reported cognitive change 17 years later in rescue/recovery workers, as was PTSD. Highly WTC-exposed subgroups may benefit from additional cognitive evaluation and monitoring of cognition over time.

Long-Term Training-Induced Gains of an Auditory Skill in School-Age Children As Compared With Adults.

The few studies that compared auditory skill learning between children and adults found variable results, with only some children reaching adult-like thresholds following training. The present study aimed to assess auditory skill learning in children as compared with adults during single- and multisession training. It was of interest to ascertain whether children who do not reach adult-like performance following a single training session simply require additional training, or whether different mechanisms underlying skill learning need to reach maturity in order to become adult-like performers. Forty children (7-9 years) and 45 young adults (18-35 years) trained in a single session. Of them, 20 children and 24 adults continued training for eight additional sessions. Each session included six frequency discrimination thresholds at 1000 Hz using adaptive forced-choice procedure. Retention of the learning-gains was tested 6 to 8 months posttraining. Results showed that (a) over half of the children presented similar performance and time course of learning as the adults. These children had better nonverbal reasoning and working memory abilities than their non-adult-like peers. (b) The best predicting factor for the outcomes of multisession training was a child's performance following one training session. (c) Performance gains were retained for all children with the non-adult-like children further improving, 6 to 8 months posttraining. Results suggest that mature auditory skill learning can emerge before puberty, provided that task-related cognitive mechanisms and task-specific sensory processing are already mature. Short-term training is sufficient, however, to reflect the maturity of these mechanisms, allowing the prediction of the efficiency of a prolonged training for a given child.

Ductal plate malformation in a nonhuman primate.

During necropsy of a 6-year-old, male African Green monkey (Cercopithecus aethiops), multifocal pale, white to tan areas, 1-2 cm in diameter, were noted in the right lateral lobe, medial lobe, and capsular surface of the liver. Light microscopic examination of the liver revealed numerous spindle cells dispersed within interconnecting, broad bands of collagen, up to 200 microm in width, which often spanned and connected portal areas. A diagnosis of hepatic ductal plate malformation, most closely resembling congenital hepatic fibrosis with von Meyenburg complexes, was made. Few cases of ductal plate malformations in domestic animals are reported in the literature. To our knowledge, this is the first case reported in a nonhuman primate.

Judgment in older adults: development and psychometric evaluation of the Test of Practical Judgment (TOP-J).

This article reports on the development and validation of a novel, objective test of judgment for use with older adults. The Test of Practical Judgment (TOP-J) is an open-ended measure that evaluates judgment related to safety, medical, social/ethical, and financial issues. Psychometric features were examined in a sample of 134 euthymic individuals with mild Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), or cognitive complaints but intact neuropsychological performance (CC), and demographically-matched healthy controls (HC). Measures of reliability were adequate to high, and TOP-J scores correlated with select measures of executive functioning, language, and memory. AD participants obtained impaired TOP-J scores relative to HCs, while MCI and CC participants showed an intermediate level of performance. Confirmatory factor analyses were consistent with a unidimensional structure. Results encourage further development of the TOP-J as an indicator of practical judgment skills in clinical and research settings. Longitudinal assessments are being performed to examine predictive validity of the TOP-J for cognitive progression in our clinical groups.

Regional brain atrophy in cognitively intact adults with a single APOE epsilon4 allele.

OBJECTIVE: To determine whether cognitively intact adults with the APOE epsilon3/epsilon4 genotype show reduced gray matter density on voxel-based morphometry (VBM) vs those homozygous for the epsilon3 allele. METHODS: Participants were healthy, cognitively intact, right-handed adults, age 19 to 80, who completed genotyping, neuropsychological testing, and MRI. Forty-nine participants had the epsilon3/epsilon3 genotype and 27 had the epsilon3/epsilon4 genotype. Gray matter data were analyzed using the general linear model as implemented in the Statistical Parametric Mapping package, adjusting for age and sex. RESULTS: The epsilon3/epsilon4 participants showed lower gray matter density than the epsilon3/epsilon3 participants in right medial temporal and bilateral frontotemporal regions as well as other areas. There were no regions in which epsilon3/epsilon4 participants showed higher gray matter density than epsilon3/epsilon3 participants. CONCLUSIONS: Regionally reduced gray matter density is detectable in cognitively intact adults with a single copy of the APOE epsilon4 allele.

Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI.

OBJECTIVE: To examine the neural basis of cognitive complaints in healthy older adults in the absence of memory impairment and to determine whether there are medial temporal lobe (MTL) gray matter (GM) changes as reported in Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI). METHODS: Participants were 40 euthymic individuals with cognitive complaints (CCs) who had normal neuropsychological test performance. The authors compared their structural brain MRI scans to those of 40 patients with amnestic MCI and 40 healthy controls (HCs) using voxel-based morphometry and hippocampal volume analysis. RESULTS: The CC and MCI groups showed similar patterns of decreased GM relative to the HC group on whole brain analysis, with differences evident in the MTL, frontotemporal, and other neocortical regions. The degree of GM loss was associated with extent of both memory complaints and performance deficits. Manually segmented hippocampal volumes, adjusted for age and intracranial volume, were significantly reduced only in the MCI group, with the CC group showing an intermediate level. CONCLUSIONS: Cognitive complaints in older adults may indicate underlying neurodegenerative changes even when unaccompanied by deficits on formal testing. The cognitive complaint group may represent a pre-mild cognitive impairment stage and may provide an earlier therapeutic opportunity than mild cognitive impairment. MRI analysis approaches incorporating signal intensity may have greater sensitivity in early preclinical stages than volumetric methods.

Clear cell carcinoid tumor of the gallbladder: another distinctive manifestation of von Hippel-Lindau disease.

We describe a morphologically distinctive carcinoid tumor of the gallbladder that occurred in a 38-year-old man with von Hippel-Lindau (VHL) disease. The carcinoid tumor was composed predominantly of lipid-containing clear cells arranged in nests and tubules with pagetoid spread into the biliary epithelium and was interpreted as metastatic renal cell carcinoma. The neoplastic cells showed diffuse immunoreactivity for chromogranin, synaptophysin, cytokeratins (cytokeratin 7 and AE1/AE3) and, unexpectedly, for inhibin, but were negative for monoclonal carcinoembryonic antigen, serotonin and a variety of peptide hormones. This clear cell carcinoid tumor of the gallbladder was histologically similar to the recently described clear cell endocrine pancreatic tumor associated with VHL. Four cases of the latter tumor, which were also inhibin positive showed, in addition, focal and variable reactivity for the pancreatic hormones. Two classical carcinoid tumors of the gallbladder, two renal cell carcinomas associated with VHL and 11 of 13 sporadic endocrine pancreatic tumors (not associated with VHL) did not show immunoreactivity for inhibin. Inhibin appears to be an immunohistochemical marker for gallbladder clear cell carcinoid and clear cell endocrine pancreatic tumors associated with VHL and is a useful tool to distinguish these tumors from metastatic renal cell carcinoma. However, the basis for the inhibin positivity in these endocrine tumors is unknown.

Auditory backward masking and the effect of training in normal hearing adults.

Recent renewed interest in auditory backward masking has stemmed from studies of children with language impairments who were found to have significant, elevated thresholds for this paradigm, compared to normal cohorts. There are, however, many unresolved theoretical and procedural issues. The present study was conducted to investigate some of these issues. Specific purposes were: 1) To establish the differences between backward masking and simultaneous masking in normal hearing subjects; 2) To investigate the effect of listening conditions, i.e., monaural versus binaural; 3) To measure the effect of training on the performance of a backward masking paradigm; and 4) To measure generalization of the trained condition to untrained conditions. Two experiments were conducted: In experiment I, we compared the performance of 10 normal-hearing adult subjects for backward masking and simultaneous masking paradigms in both monaural and binaural modes of presentation. Stimuli consisted of a 1000 Hz pure-tone and bandpass masker (600-1400 Hz). Tone thresholds for backward masking were significantly lower than those of the simultaneous masking. The binaural mode of presentation yielded lower thresholds than those of the monaural mode only for the backward masking condition. A significantly large inter- and intra-subject variability was observed in the backward masking paradigm. Experiment II was conducted to measure the effects of training and generalization. Two groups of subjects were included: a trained group and a control group of six and eight normal hearing adults, respectively. The trained group received 10 sessions of backward masking training with feedback. The control group was tested only twice, with a 2-week interval between testing. Only the trained group showed a significant improvement in backward masking thresholds, which amounted to an average of 10.7 dB. No significant improvement was observed in the non-trained group. A nonsignificant trend of generalization occurred for the trained task to the untrained ear. No generalization was evident in the untrained condition (simultaneous masking). The data have important clinical and theoretical implications regarding the ability to train for auditory tasks in general, and for backward masking in particular.

Pitch discrimination: are professional musicians better than non-musicians?

Musicians are typically considered to exhibit exceptional auditory skills. Only few studies, however, have substantiated this in basic psychoacoustic tasks. The purpose of the present investigation was to expand our knowledge on basic auditory abilities of musicians compared to non-musicians. Specific goals were: (1) to compare frequency discrimination thresholds (difference limen for frequency [DLF]) of non-musical pure tones in controlled groups of professional musicians and non-musicians; (2) to relate DLF performance to musical background; and (3) to compare DLF thresholds obtained with two threshold estimation procedures: 2- and 3- interval forced choice procedures (2IFC and 3IFC). Subjects were 16 professional musicians and 14 non-musicians. DLFs were obtained for three frequencies (0.25, 1 and 1.5 kHz) using the 3IFC adaptive procedure, and for one frequency (1 kHz) also using the 2IFC. Three threshold estimates were obtained for each frequency, procedure and subject. The results of the present study support five major findings: (a) mean DLFs for musicians were approximately half the values of the non-musicians; (b) significant learning for both groups during the three threshold estimations; (c) classical musicians performed better than those with contemporary musical background; (d) performance was influenced by years of musical experience; and (e) both groups showed better DLF in a 2IFC paradigm compared to the 3IFC. These data highlight the importance of short-term training on an auditory task, auditory memory and factors related to musical background (such as musical genre and years of experience) on auditory performance.

Speech perception results--the first 10 years of a cochlear implant program.

Long-term speech perception test results for prelingually deaf children were compared with those of postlingually deafened adults, both groups having undergone cochlear implant at our Center. Average open-set score results of adults were similar to those of the children. However, some qualitative differences were demonstrated on the perception of phonological contrasts between the groups.

A test of the overconfidence phenomenon using audio signals.

The existence of the overconfidence phenomenon was examined using a signal detection paradigm. Fifty-five participants were asked to decide whether they heard a signal or noise only, and to rate how certain they were of their decisions. The results confirmed the existence of overconfidence as well as the "hard-easy" effect.

Hemochromatosis (HFE) gene sequence analysis of formalin-fixed, paraffin-embedded liver biopsy specimens.

BACKGROUND: Hereditary hemochromatosis (HH) is a common disease predominantly characterized by mutations of the HFE gene. METHODS AND RESULTS: We investigated the utility of HFE gene sequence analysis in the diagnosis of HH in 61 prospectively accrued formalin-fixed, paraffin-embedded liver biopsy specimens with clinical or histologic features suggestive of HH. Mutations in codons 63 or 282 of the HFE gene were identified by direct sequencing; in 21 of these samples, quantitative hepatic iron testing was also performed. Changes characteristic of HH were present in 16 (26%) of the cases, and 54% of the cases showed HFE gene mutations. The most common alteration was homozygous mutation of codon 282 (11 cases, 18%), followed by the combined 63 + 282 heterozygous mutation (3 cases, 5%). Two cases (3%) showed biallelic mutation of codon 63. The other 28 cases (46%) showed no sequence abnormalities. Weak iron staining did not exclude HH; intense staining did not reliably predict HH. CONCLUSION: When HH is clinically and/or histologically suspected, HFE gene sequencing of formalin-fixed, paraffin-embedded liver biopsy specimens is a rapid and cost-effective approach to genotypic diagnosis of HH.

Speech perception test for Arabic-speaking children.

The high incidence of hearing impairment in the Arabic-speaking population in Israel, as well as the use of advanced aural rehabilitation devices, motivated the development of Arabic speech assessment tests for this population. The purpose of this paper is twofold. The first goal is to describe features that are unique to the Arabic language and that need to be considered when developing such speech tests. These include Arabic diglossia (i.e., the sharp dichotomy between Literary and Colloquial Arabic), emphatization, and a simple vowel system. The second goal is to describe a new analytic speech test that assesses the perception of significant phonological contrasts in the Colloquial Arabic variety used in Israel. The perception of voicing, place, and manner of articulation, in both initial and final word positions, was tested at four sensation levels in 10 normally-hearing subjects using a binary forced-choice paradigm. Results show a relationship between percent correct and presentation level that is in keeping with articulation curves obtained with Saudi Arabic and English monosyllabic words. Furthermore, different contrasts yielded different articulation curves: emphatization was the easiest to perceive whereas place of articulation was the most difficult. The results can be explained by the specific acoustical features of Arabic.

Identification of the relative onset time of a two-tone complex: auditory sensitivity or language based?

Categorical perception occurs when equal physical differences on a continuum sometimes cause no changes in the identification of a stimulus, while at other points on the same continuum, that difference causes an abrupt change in perception. One of the unresolved issues regarding this phenomenon is what determines categorical perception: a special speech mode or "natural" psychophysical boundaries. One way to answer this question is by investigating categorical perception with non-speech stimuli. An example is the identification of the relative onset of a two-tone complex (TOT) analogous to voice-onset time (VOT), the acoustic cue to voicing in initial position. Studies in English found similar category boundaries for TOT and VOT (at +20 ms) supporting the non-speech specific theory. The purpose of this study was to investigate TOT in Hebrew-speaking listeners whose language uses very different VOT values from those reported in English. Twenty Hebrew-speaking young adults participated in this study. Stimuli consisted of a two-tone complex that varied in the relative onset time of the lower tone from a lead of -50 ms to a lag of +50 ms in 10 ms steps. Results show that: (1) All subjects were able to identify the lag conditions from the simultaneous ones but only half of them were also able to identify the lead from the simultaneous ones. This was explained in terms of prominent pitch cues available when shifting from simultaneous to lagging stimuli. (2) Hebrew category boundaries (CBs) for TOT are shorter than those of VOT, and both are shorter than the respective English ones. Nonetheless, all CBs fell into the range of 10 to 30 ms. The data support the hypothesis that "natural" psychophysical boundaries determine categorical perception but behavioral measures may be influenced by speech.

Age-related changes in the visual perception of phonologically significant contrasts.

The purpose of the present study was to determine whether the ability to speechread phonological contrasts is influenced by age. Forty-eight subjects were equally represented in three age groups: 8-9 years, 11-12 years and adults (20-29 years). The Hebrew version of the Speech Pattern Contrast (HeSPAC) test was administered by speechreading alone. Results showed that: age influenced performance; performance was contrast-dependent (place contrasts highly visible, manner and vowel height partially visible and voicing contrast invisible); hierarchy of contrast performance was similar for all age groups; Hebrew and English differ in the visual accessibility to speech contrasts in final voicing only; and females were found to be poorer speechreaders than males for the partially visible contrasts. The results suggest that speechreading at the phonological level follows a developmental course. The implications of these findings extend to recommendations provided to children in noisy listening conditions, speechreading training in hearing-impaired children and those with central auditory processing disorders (CAPD), and to the design of sensory aids.

Verb generation priming involves conceptual implicit memory.

Brain activation patterns differ and generation latencies are reduced when generating verbs to repeated nouns (Raichle et al., 1994). Amnesic participants show normal magnitude of priming (Seger et al., 1997). Despite its importance in neuropsychology, verb generation priming is not well characterized psychologically. Six behavioral studies found that verb generation priming was specific to the verb rather than to the noun or the noun-verb pair, was equivalent after overt or covert generation and after reading verbs or generating verbs, was affected by levels of processing, and transferred completely across languages in bilinguals. These results indicate that verb generation priming involves priming of particular responses and happens at a conceptual level. These findings provide new insights about the significance of brain imaging and neuropsychological studies involving verb generation priming.

The effect of partially restored hearing on speech production of postlingually deafened adults with multichannel cochlear implants.

The effect of auditory feedback on speech production was investigated in five postlingually deafened adults implanted with the 22-channel Nucleus device. Changes in speech production were measured before implant and 1, 6, and 24 months postimplant. Acoustic measurements included: F1 and F2 of vowels in word-in-isolation and word-in-sentence context, voice-onset-time (VOT), spectral range of sibilants, fundamental frequency (F0) of word-in-isolation and word-in-sentence context, and word and sentence duration. Perceptual ratings of speech quality were done by ten listeners. The significant changes after cochlear implantation included: a decrease of F0, word and sentence duration, and F1 values, and an increase of voiced plosives' voicing lead (from positive to negative VOT values) and fricatives' spectral range. Significant changes occurred until 2 years postimplant when most measured values fell within Hebrew norms. Listeners were found to be sensitive to the acoustic changes in the speech from preimplant to 1, 6, and 24 months postimplant. Results suggest that when hearing is restored in postlingually deafened adults, calibration of speech is not immediate and occurs over time depending on the age-at-onset of deafness, years of deafness, and perception skills. The results also concur with hypothesis that the observed changes of some speech parameters are an indirect consequence of intentional changes in other articulatory parameters.

The perception of phonologically significant contrasts using speech envelope cues.

The observation that many cochlear implantees demonstrate high levels of speech recognition, despite limited or distorted spectral information, has motivated research on the importance of temporal information for the perception of speech. The purpose of this study was to measure the recognition of speech contrasts via only the speech envelope before and after training. Test stimuli consisted of eight segmental and two suprasegmental contrasts of the Hebrew Speech Pattern Contrast test using a binary forced-choice paradigm. Multiplying the speech waveform with white noise eliminated spectral information. Results show that stress, intonation and manner of articulation were very well perceived using only temporal information, whereas voicing and place of articulation were perceived above chance levels. Results also show that vowels were more susceptible to the removal of spectral information than consonants. These findings help to better understand speech perception performance of hearing-impaired individuals, including cochlear implant users. They may also have practical implications for aural rehabilitation and sensory aids design for the Hebrew speaking population.

A brief medical necessity scale for mental disorders: reliability, validity, and clinical utility.

Managed care organizations (MCOs) use the concept of "medical necessity" to decide whether a prescribed treatment is warranted for a given medical condition. Because mental disorders lack the objective disease criteria common to medical illness, behavioral health administrators need a validated means to identify and quantify the severity of "medically important" aspects of mental disorders. The authors developed and tested a brief medical necessity scale for mental disorders in 205 patients presenting for initial evaluation. The scale had a factor structure with four subscales; good internal consistency, interrater reliability, and concurrent and predictive validity; and modest ability to identify patients requiring hospitalization and, in hospitalized patients, those requiring involuntary hospitalization. The authors propose use of the scale to better clarify decisions about level of care assignments and to better assess patient characteristics predictive of good outcome.