Preliminary Evidence that Memantine Enhances Prepulse Effects on Startle Magnitude and Latency in Patients with Alzheimer's Disease.

BACKGROUND: The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer's disease (AD); conceivably, its acute impact on PPI might be used to predict a patient's sensitivity to MEM's therapeutic effects. OBJECTIVE: To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients. METHODS: 18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency. RESULTS: Fifteen out of 18 participants exhibited reliable startle responses. MEM did not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p < 0.04; d = 0.40); this comparison reached a large effect size for the 60 ms interval (d = 0.62), where maximal MEM effects on PPI were previously detected. Prepulses reduced peak startle latency ("latency facilitation") and this effect was amplified after MEM (p = 0.03; d = 0.41; for 60 ms intervals, d = 0.69). No effects of MEM were detected on cognition, nor were MEM effects on startle associated with cognitive or clinical measures. CONCLUSION: MEM enhances prepulse effects on startle magnitude and latency in AD; these changes in PPI and latency facilitation with MEM suggest that these measures can be used to detect an AD patient's neural sensitivity to acute MEM challenge. Studies in progress will determine whether such a "biomarker" measured at the outset on treatment can predict sensitivity to MEM's therapeutic effects.

Using Biomarkers to Predict Memantine Effects in Alzheimer's Disease: A Proposal and Proof-Of-Concept Demonstration.

Memantine's benefits in Alzheimer's disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual's clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid). Study participation was well tolerated. Subgroups based on memantine sensitivity on specific laboratory measures differed in their clinical response to memantine, some by large effect sizes. It appears feasible to use biomarkers to predict clinical sensitivity to memantine.

Meaning in Life and Its Relationship With Physical, Mental, and Cognitive Functioning: A Study of 1,042 Community-Dwelling Adults Across the Lifespan.

OBJECTIVE: To examine the relationship of presence and search for meaning in life with age, physical and mental well-being, and cognitive functioning across the adult lifespan. METHODS: Cross-sectional data from 1,042 adults in the Successful AGing Evaluation (SAGE)-a multicohort study of adult community-dwelling residents of San Diego County, California-were analyzed. Presence of meaning ("Presence") and search for meaning in life ("Search") were assessed with the Meaning in Life Questionnaire. Physical and mental well-being were measured using the Short Form 36 Health Survey (SF-36). Telephone Interview for Cognitive Status-modified was employed to screen for overall cognitive function. Study data were collected from January 2013 to June 2014. RESULTS: Presence of meaning exhibited an inverted U-shaped relationship whereas Search showed a U-shaped relationship with age (with Presence peaking and Search reaching the lowest point around age 60). Statistical modeling using generalized estimating equations revealed that physical well-being (SF-36 physical composite score) correlated negatively with age (P < .001) and positively with Presence (P < .001), and there was an age group x Presence interaction (P = .018), such that the relationship was stronger in subjects over age 60. Mental well-being correlated positively with age (P < .001) and Presence (P < .001) and negatively with Search (P = .002). Cognitive function correlated inversely with age (P < .001) and with Search (P < .001). Significant covariates of Presence and Search had small effect sizes, except for a medium effect size for satisfaction with life and Presence in adults over age 60 (P < .001). CONCLUSIONS: Presence and search for meaning in life are important for health and well-being, though the relationships differ in adults younger and older than 60 years. Better understanding of the longitudinal relationships of meaning of life with well-being is warranted to design interventions to increase meaning of life and improve health and functioning.

Complex Clinical Intersection: Palliative Care in Patients with Dementia.

Because of the rapidly growing older population and increases in longevity, rates of dementia have been rising. Clinical challenges of treating dementia include limited resources and lack of curative therapies. Palliative care approaches improve quality of life and alleviate suffering for dementia patients at the end of life, although implementation may be limited by societal acceptance and feasibility. This review examines the published literature on pain assessments, pain and behavior interventions, tools for advanced care planning, and clinical concerns in dementia patients. Ultimately, modification of the traditional palliative care model may improve outcomes and functioning for dementia patients at all stages of their illness.

Effect of short-term research training programs on medical students' attitudes toward aging.

Strategies to build a larger workforce of physicians dedicated to research on aging are needed. One method to address this shortage of physician scientists in geriatrics is short-term training in aging research for early-stage medical students. The authors examined the effects of two summer research training programs, funded by the National Institutes of Health, on medical students' attitudes toward aging, using the Carolina Opinions on Care of Older Adults (COCOA). The programs combined mentored research, didactics, and some clinical exposure. In a sample of 134 participants, COCOA scores improved significantly after completion of the research training program. There was a significant interaction of gender, such that female students had higher baseline scores than males, but this gender difference in COCOA scores was attenuated following the program. Four of the six COCOA subscales showed significant improvement from baseline: early interest in geriatrics, empathy/compassion, attitudes toward geriatrics careers, and ageism.

Person-Centered Care for Older Adults With Serious Mental Illness and Substance Misuse Within a Program of All-Inclusive Care for the Elderly.

Providing person-centered care (PCC) to older adults with dual diagnosis, co-occurring serious mental illness (SMI), and substance misuse is complex and requires an interprofessional team. Older adults, who qualify for both Medicaid and Medicare (i.e., dual-eligibles) are overrepresented in the population of older adults with SMI and substance misuse. Programs of All-Inclusive Care for the Elderly (PACE) exist to support community living needs of nursing home-eligible older adults and are increasingly in a position to serve older adults with SMI and substance misuse issues. PACE programs provide integrated person-centered mental health care to address the serious medical, social, and emotional complications posed by having SMI and substance misuse disorders. The case study presented illustrates PCC provided to a dual-diagnosis PACE participant, illustrating the impact of recent and past trauma on current psychopathology and substance misuse. Finally, recommendations for addressing PCC of dual diagnosis within the PACE model are provided. [Journal of Gerontological Nursing, 42(5), 11-17.].