Effect of a computerized brain exercise program on cognitive performance in older adults.

OBJECTIVES: Research indicates an association between stimulating mental activities and better memory performance as people age, but studies on computerized mental stimulation programs are limited. We explored whether computerized brain training exercises improved cognitive performance in older adults. METHODS: In local retirement communities, a convenience sample was randomized into an intervention group (N = 36), who used a computer program 5 days a week for 20-25 minutes each day, or a wait-list control group (N = 33). All were older adults without dementia (mean age: 81.8 years; SD: 6.1; 67% female). Neuropsychological testing was completed at baseline (Time 1), 2 months (Time 2), and 6 months (Time 3). Three cognitive domains (Immediate Memory, Delayed Memory, Language) were compared in the two groups as a function of time using mixed models. RESULTS: The intervention group used the computerized program (Brain Fitness, Dakim Inc., Santa Monica, CA) for an average of 43 (SD: 4.4) sessions by Time 2 and 81 (SD: 37.5) sessions by Time 3. Mixed models examining cognitive domains as function of time revealed significant group differences in Delayed Memory (F(2,72) = 4.7, p = 0.01) but not Immediate Memory and Language; no significant improvements were noted for the control group. Among all participants, anyone playing at least 40 sessions over the 6 months improved in all three domains (Immediate Memory, Delayed Memory, and Language). CONCLUSION: Participating in a computerized brain exercise program over 6 months improves cognitive abilities in older adults. These results extend literature indicating the benefit of training exercises, whether in a classroom format or via a computerized self-paced program.

Self-reported memory impairment and brain PET of amyloid and tau in middle-aged and older adults without dementia.

BACKGROUND: Whether perceived changes in memory parallel changes in brain pathology is uncertain. Positron emission tomography (PET) scans using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) can measure levels of amyloid plaques and tau neurofibrillary tangles in vivo. Here we investigate whether degree of self-reported memory impairment is associated with FDDNP-PET binding levels in persons without dementia. METHODS: Fifty-seven middle-aged and older adults without dementia (mean age ±standard deviation = 66.3 ± 10.6 years), including 25 with normal aging and 32 with mild cognitive impairment (MCI), were assessed. The outcome measures were the four factor scores of the Memory Functioning Questionnaire (MFQ) (frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use) and FDDNP-PET binding levels in medial temporal, lateral temporal, posterior cingulate, parietal, frontal, and global (overall average) regions of interest. RESULTS: After controlling for age, higher reported frequency of forgetting was associated with greater medial temporal (r = -0.29, p = 0.05), parietal (r = -0.30, p = 0.03), frontal (r = -0.35, p = 0.01), and global FDDNP-PET binding levels (r = -0.33, p = 0.02). The remaining MFQ factor scores were not significantly associated with FDDNP-PET binding levels, and no significant differences were found between normal aging and MCI subjects. Item analysis of the frequency of forgetting factor revealed five questions that yielded similar results as the full 32-question scale (r = -0.52, p = 0.0002). CONCLUSIONS: These findings suggest that some forms of memory self-awareness, in particular the reported frequency of forgetting, may reflect the extent of cerebral amyloid and tau brain pathology.

Differential FDDNP PET patterns in nondemented middle-aged and older adults.

OBJECTIVE: The authors explored whether positron emission tomography (PET) with 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl) amino]-2-naphthyl} ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, might identify homogeneous subgroups of persons in middle-aged and older persons with mild cognitive impairment (MCI) or normal cognition. PARTICIPANTS: Fifty-six subjects (MCI, N = 29; normal cognition, N = 27). MEASUREMENTS: FDDNP-PET scans were performed. Logan parametric images were produced using cerebellum as a reference region, and relative distribution volumes were obtained for regions of interest (ROIs) known to accumulate plaques and tangles in Alzheimer disease (AD). Cluster analysis was used to identify subgroups of subjects according to FDDNP signal distribution. Once the FDDNP clusters were identified, the authors then characterized the clusters also with respect to diagnosis and cognitive test performances and conducted analyses on cluster differences in these variables. RESULTS: The authors identified three FDDNP clusters: high signal in lateral temporal and posterior cingulate ROIs (high temporal-posterior cingulate HT/PC); low signal in all ROIs (low global [LG] cluster); high frontal and parietal signal with intermediate temporal and posterior cingulate signal (HF/PA). Most MCI subjects belonged to the HT/PC and HF/PA clusters, whereas most cognitively normal subjects were in the LG cluster. On cognitive tests, the HT/PC and the HF/PA clusters performed significantly worse than LG but did not significantly differ from each other. CONCLUSIONS: This approach may be useful in identifying potential high-risk imaging cluster patterns. Longitudinal follow-up would be performed to determine the association of these subgroups with diagnostic and functional outcome.

The role of cytoprotective cytokines in cardiac ischemia/reperfusion injury.

The mechanism(s) underlying the beneficial effects of adult mesenchymal stem cells (MSCs) after myocardial infarction (MI) is poorly understood. One possible explanation is the ability of MSCs to secrete cytokines, which modulate cardiomyocyte survival and function. MSCs express at least two cytoprotective cytokines, hepatocyte growth factor (HGF) and stromal cell-derived factor-1 alpha (CXCL12). The aim of our study was to compare the effects of these two cytokines administered acutely post-MI. We subjected adult male Lewis rats to myocardial ischemia/reperfusion injury. Immediately upon reperfusion, polymers saturated with HGF or CXCL12 were placed onto the infarcted anterior wall and the rats were allowed to recover. Echocardiographic analysis at 4 wk post-MI to assess left ventricular (LV) function revealed that LV ejection fraction was increased in the HGF treated group compared with the phosphate-buffered saline (PBS) control group. Likewise, LV end diastolic dimension was reduced in the HGF treated group compared with the PBS control group. Similarly, invasive hemodynamics at 12 wk showed improved contractility and relaxation in the HGF treated group compared with the PBS control group. In contrast, no significant effect on LV function was seen in the CXCL12 treated group. To determine the potential mechanism for this effect, infarct size (IFS) at 72 h was determined. IFS was decreased 4.2-fold in the HGF treated group compared with the PBS control group. Thus, HGF acutely post-MI using polymer delivery reduces IFS, leading to beneficial effects on post-MI LV remodeling.

Anxiety and verbal memory performance in APOE-4 carriers and noncarriers aged 50 years and above.

AIMS: The current study sought to explore the relationship between state and trait anxiety and delayed verbal memory performance in APOE-4 carriers and noncarriers who were aged 50 years and above. MATERIALS #ENTITYSTARTX00026; METHODS: The study was a retrospective analysis of 267 participants aged 50 years and above who had completed genetic testing for APOE status, the State-Trait Anxiety Inventory, and a comprehensive neuropsychological battery that included three delayed verbal memory measures (Wechsler Memory Scale - 3rd Edition, Logical Memory and Verbal Pairs subtests and the Buschke Selective Reminding Test). RESULTS: An inverse relationship was found between state anxiety and delayed verbal memory performance. No difference in level of anxiety was found between APOE-4 carriers versus noncarriers. CONCLUSION: State anxiety, but not trait anxiety, was found to have an inverse relationship with delayed verbal memory performance. For example, as self-reported state anxiety increased, delayed verbal memory scores decreased. This relationship did not appear to be influenced by the presence or absence of the APOE-4 allele.

Prediction of cognitive decline by positron emission tomography of brain amyloid and tau.

OBJECTIVE: To determine whether 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) brain regional values in individuals without dementia predict and correlate with future cognitive change. DESIGN: Two-year, longitudinal follow-up study. SETTING: A university research institute. PARTICIPANTS: Volunteer sample of 43 middle-aged and older persons (median age, 64 years), including 21 with mild cognitive impairment (MCI) and 22 with normal aging. MAIN OUTCOME MEASURES: Longitudinal [(18)F]FDDNP positron emission tomography (PET) binding values in the medial and lateral temporal, posterior cingulate, parietal, frontal, and global (mean) regions of interest; neuropsychological test battery measuring 5 cognitive domains, including memory, language, attention (and information-processing speed), executive functioning, and visuospatial ability. RESULTS: For the entire study group (MCI and normal aging), increases in frontal, posterior cingulate, and global binding at follow-up correlated with progression of memory decline (r = -0.32 to -0.37, P = .03 to .01) after 2 years. Moreover, higher baseline [(18)F]FDDNP binding was associated with future decline in most cognitive domains, including language, attention, executive, and visuospatial abilities (r = -0.31 to -0.56, P = .05 to .002). For the MCI group, frontal and parietal [(18)F]FDDNP binding yielded the greatest diagnostic accuracy in identifying converters to Alzheimer disease vs nonconverters after 2 years, with an area under the receiver operating characteristic curve of 0.88 (95% CI, 0.72-1.00) compared with 0.68 (95% CI, 0.45-0.91) for medial temporal binding. CONCLUSIONS: [(18)F]FDDNP PET regional binding patterns are consistent with known neuropathologic patterns of plaque and tangle brain accumulation, spreading from the medial temporal to other neocortical regions as disease progresses. Because binding patterns predict future cognitive decline and increase over time along with clinical decline, [(18)F]FDDNP PET scanning may have practical utility in identifying people at risk for future cognitive decline and in tracking the effectiveness of novel interventions designed to prevent or delay neurodegeneration and cognitive decline.

Comparing isoflurane with tribromoethanol anesthesia for echocardiographic phenotyping of transgenic mice.

Cardiac phenotyping of transgenic mice typically requires anesthesia. Chemical-grade tribromoethanol (TBE) is commonly used for this purpose due to its relatively short duration of action, modest cardiodepressive effects, and its noncontrolled status. In the present study, we used both genders of C57BL/6;C3H-Tg(Slc8a1)hKdp transgenic (TG) mice and C57BL/6;C3H wild-type (WT) mice to evaluate isoflurane (ISF) as a pharmaceutical-grade alternative to TBE for echocardiography and electrocardiography. Baseline target physiologic heart rates (beats per minute) were established by use of telemetry as 544 +/- 10 in WT mice and 580 +/- 21 in TG mice. TG and WT animals were anesthetized with either 0.8% to 1% inhalational ISF or 250 mg/kg intraperitoneal TBE. The following parameters were measured or calculated according to the previously defined physiologic heart rates: end diastolic and systolic dimensions; posterior wall and ventricular septal thicknesses; left ventricular mass, aortic ejection times; left ventricular fractional shortening; velocity of circumferential fiber shortening; and left ventricular ejection fraction. No significant difference between anesthetics was found for any measured cardiac parameters. However, the time required for data acquisition was significantly shorter for ISF (10 min) than for TBE (14 min). This study demonstrates that comparable echocardiographic results can be obtained at higher throughput by use of pharmaceuticalgrade ISF than with chemical-grade TBE.