Investigation of potential cognitive tests for use with older adults in audiology clinics.

BACKGROUND: Cognitive declines in working memory and processing speed are hallmarks of aging. Deficits in speech understanding also are seen in aging individuals. A clinical test to determine whether the cognitive aging changes contribute to aging speech understanding difficulties would be helpful for determining rehabilitation strategies in audiology clinics. PURPOSE: To identify a clinical neurocognitive test or battery of tests that could be used in audiology clinics to help explain deficits in speech recognition in some older listeners. RESEARCH DESIGN: A correlational study examining the association between certain cognitive test scores and speech recognition performance. Speeded (time-compressed) speech was used to increase the cognitive processing load. STUDY SAMPLE: Two hundred twenty-five adults aged 50 through 75 years were participants in this study. Both batteries of tests were administered to all participants in two separate sessions. DATA COLLECTION AND ANALYSIS: A selected battery of neurocognitive tests and a time-compressed speech recognition test battery using various rates of speech were administered. Principal component analysis was used to extract the important component factors from each set of tests, and regression models were constructed to examine the association between tests and to identify the neurocognitive test most strongly associated with speech recognition performance. RESULTS: A sequencing working memory test (Letter-Number Sequencing [LNS]) was most strongly associated with rapid speech understanding. The association between the LNS test results and the compressed sentence recognition scores (CSRS) was strong even when age and hearing loss were controlled. CONCLUSIONS: The LNS is a sequencing test that provides information about temporal processing at the cognitive level and may prove useful in diagnosis of speech understanding problems, and in the development of aural rehabilitation and training strategies.

Development of vaccines and passive immunotherapy against SARS coronavirus using mouse and SCID-PBL/hu mouse models.

We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD-SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The M DNA vaccine enhanced CTL activity and proliferation in the presence of M peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL activity (IFN-gamma production by recombinant N protein or N protein-pulsed autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice. These results, demonstrate that SARS M and N DNA vaccines induced human CTL and human T-cell proliferative responses. On the other hand, we have developed SARS DNA vaccines that induce human neutralizing antibodies and human monoclonal antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor (angiotensin converting enzyme 2) are also under development. These vaccines are expected to induce immune responses specific for SARS CoV in human and should provide useful tool for development of protective vaccines.

Sequencing versus nonsequencing working memory in understanding of rapid speech by older listeners.

The goal of this study was to identify specific neurocognitive deficits that are associated with older listeners' difficulty understanding rapid speech. Older listeners performed speech recognition tests comprised of time-compressed sentences with and without context, and on a neurocognitive battery aimed specifically at testing working memory, processing speed, and attention. A principle component analysis identified three main cognitive components as follows: a sequencing working memory (WM-S) component, a nonsequencing working memory (WM-NS) component, and a processing speed (PS) component. Each of the cognitive component scores was divided into high, mid, and low categories. Sentence performance of the cognitive subgroups was compared within each component. The results showed that, with hearing loss and age accounted for, the cognitive score groups differed similarly on the sentence condition scores also at 50 and 60% time compression, particularly on the subgroups of the WM-S component. The results suggest that deficits in a separate working memory function identified as sequencing were associated with differences in ability to understand time-compressed speech in this study.

Novel recombinant BCG and DNA-vaccination against tuberculosis in a cynomolgus monkey model.

We have developed two novel tuberculosis (TB) vaccines: a DNA vaccine combination expressing mycobacterial heat shock protein 65 (Hsp65) and interleukin-12 (IL-12) by using the hemagglutinating virus of Japan (HVJ)-liposome (HSP65+IL-12/HVJ) and a recombinant BCG harboring the 72f fusion gene (72f rBCG). These vaccines provide remarkable protective efficacy in mouse and guinea pig models, as compared to the current by available BCG vaccine. In the present study, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis, to evaluate the HSP65+IL-12/HVJ and 72f rBCG vaccines. Vaccination with HSP65+IL-12/HVJ as well as 72f rBCG vaccines provided better protective efficacy as assessed by the Erythrocyte Sedimentation Rate, chest X-ray findings and immune responses than BCG. Most importantly, HSP65+IL-12/HVJ resulted in an increased survival for over a year. This is the first report of successful DNA vaccination and recombinant BCG vaccination against M. tuberculosis in the monkey model.

The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice.

We have investigated to develop novel vaccines against SARS CoV using cDNA constructs encoding the structural antigen; spike protein (S), membrane protein (M), envelope protein (E), or nucleocapsid (N) protein, derived from SARS CoV. Mice vaccinated with SARS-N or -M DNA using pcDNA 3.1(+) plasmid vector showed T cell immune responses (CTL induction and proliferation) against N or M protein, respectively. CTL responses were also detected to SARS DNA-transfected type II alveolar epithelial cells (T7 cell clone), which are thought to be initial target cells for SARS virus infection in human. To determine whether these DNA vaccines could induce T cell immune responses in humans as well as in mice, SCID-PBL/hu mice was immunized with these DNA vaccines. As expected, virus-specific CTL responses and T cell proliferation were induced from human T cells. SARS-N and SARS-M DNA vaccines and SCID-PBL/hu mouse model will be important in the development of protective vaccines.

Time-expanded speech and speech recognition in older adults.

Speech understanding deficits are common in older adults. In addition to hearing sensitivity, changes in certain cognitive functions may affect speech recognition. One such change that may impact the ability to follow a rapidly changing speech signal is processing speed. When speakers slow the rate of their speech naturally in order to speak clearly, speech recognition is improved. The acoustic characteristics of naturally slowed speech are of interest in developing time-expansion algorithms to improve speech recognition for older listeners. In this study, we tested younger normally hearing, older normally hearing, and older hearing-impaired listeners on time-expanded speech using increased duration and increased intensity of unvoiced consonants. Although all groups performed best on unprocessed speech, performance with processed speech was better with the consonant gain feature without time expansion in the noise condition and better at the slowest time-expanded rate in the quiet condition. The effects of signal processing on speech recognition are discussed.