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Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21), or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug delivery device. Results revealed a treatment effect for the memory composite for the 40 IU group compared with placebo (p < 0.05). This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-ε4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02). Significant treatment effects were also apparent for verbal working memory (p < 0.03) and visuospatial working memory (p < 0.04), reflecting improvement for subjects who received the high dose of intranasal insulin detemir. No significant differences were found for daily functioning or executive functioning. In conclusion, daily treatment with 40 IU insulin detemir modulated cognition for adults with AD or MCI, with APOE-related differences in treatment response for the primary memory composite. Future research is needed to examine the mechanistic basis of APOE-related treatment differences, and to further assess the efficacy and safety of intranasal insulin detemir.

Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer’s disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers.Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD.Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer’s Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers.Results: The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio.Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.

A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE ε4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial’s 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment. On delayed story memory, men and women showed cognitive improvement when taking 20 IU of intranasal insulin, but only men showed cognitive improvement for the 40 IU dose. The sex difference was most apparent for ApoE ε4 negative individuals. For the 40 IU dose, ApoE ε4 negative men improved while ApoE ε4 negative women worsened. Their ApoE ε4 positive counterparts remained cognitively stable. This sex effect was not detected in functional measures. However, functional abilities were relatively preserved for women on either dose of intranasal insulin compared with men. Unlike previous studies with young adults, neither men nor women taking intranasal insulin exhibited a significant change in weight over 4 months of treatment.

This study examines changes in leisure patterns across the transition to parenthood for dual-earner, working-class couples, as well as the relationship between leisure and marital quality. To this end, 147 heterosexual couples were interviewed across the transition to parenthood. Findings indicate that during the transition to parenthood, husbands and wives experience an initial decline in leisure, followed by a gradual incline after the wife's return to work. Overall, wives who reported more shared leisure prenatally also reported more marital love and less conflict 1 year later. Husbands with more independent leisure prenatally reported less love and more conflict 1 year later. Conclusions suggest leisure time is integral to well-functioning marriages, with effects lasting throughout the first year of parenthood.

This study examines the three facets of psychological resilience (i.e., perceived control, commitment to living, challenge versus stability) as predictors of depressive symptoms over time among spousal caregivers of persons with Alzheimer disease; these resilience factors were considered over and above dementia-related and socio-demographic control variables. A sample of 105 cohabiting spouses of persons diagnosed with probable or possible Alzheimer disease was recruited for this study. Multilevel modeling enabled us to examine baseline resilience, and the direction and magnitude of change in resilience over time, as distinct predictors of depressive symptoms one year later, and change in depressive symptoms between points of measurement. Both Time 1 control and challenge predicted lower levels of depressive symptoms one year later; furthermore, an increase in challenge over this interval predicted lower Time 2 depressive symptoms. In contrast, commitment did not emerge as a statistically significant predictor of caregiver depression. Findings of this study provide general support for the stress process model of caregiving; in particular, the central role of intra-psychic factors as significant predictors of depressive symptoms over time.

Existing cross-sectional research demonstrates an association between reminiscence functions and well-being in later life. The results of this study replicate and extend previous findings in separate participant samples above and below 70 years of age. Findings suggest a link between reminiscence functions and psychological well-being, and indirectly between reminiscence and well-being 16 months thereafter. Invariance analyses reveal few differences in association between reminiscence and well-being when young-old (n = 196) and older adults (n = 215) are compared. These findings suggest a direct positive association between self-positive reminiscence functions (identity, death preparation, and problem-solving) and a direct negative association between self-negative functions (boredom reduction, bitterness revival, and intimacy maintenance) and psychological well-being (life satisfaction, depressive, and anxiety symptoms). In contrast, prosocial reminiscence functions (conversation, teach/inform others) appear to have an indirect association with well-being (i.e., via self-positive and self-negative functions). These findings are discussed relative to evolving theory and research linking cognition and health.

In this study of 125 heterosexual long-wed couples, we examined both spouses' personality traits and relative differences in partner perceptions of personality as predictors of marital satisfaction, simultaneously for both husbands and wives. As hypothesized, each of the Big Five personality traits emerged as significantly associated with marital satisfaction though significant between-trait and between-sex differences were observed. Most notably, trait levels predicted marital satisfaction less consistently than positive reporting discrepancies (i.e., comparatively greater extraversion, openness to experience, agreeableness, conscientiousness, and lower neuroticism reported by spouses vis-à-vis their partners' self-descriptions). While previous research points to a central role of neuroticism, our findings suggest that conscientiousness is the trait most broadly associated with marital satisfaction in this sample of long-wed couples. These differences between study findings may reflect change over the course of married life, the degree to which neuroticism determines divorce, overreliance on younger samples in previous marital research, or some combination of these three.