%0 Journal Article %J J Alzheimers Dis %D 2017 %T Dynamics of Frailty and Cognition After Age 50: Why It Matters that Cognitive Decline is Mostly Seen in Old Age. %A Godin, Judith %A Armstrong, Joshua J %A Rockwood, Kenneth %A Andrew, Melissa K %X

BACKGROUND: Frailty has been considered an antecedent and, to a lesser extent, an outcome of cognitive impairment. Both frailty and cognitive impairment are multiply determined and each is strongly related to age, making it likely that the two interact, especially as people age. In consequence, understanding their interaction and co-occurrence can offer insight into pathophysiology, prevention, and management.

OBJECTIVE: To examine the nature of the relationship between frailty and cognitive impairment using longitudinal data from the Survey of Health Aging and Retirement in Europe (SHARE), assessing for bidirectionality.

METHODS: We conducted secondary analyses using data from the first two waves of SHARE. The sample (N = 11,941) was randomly split into two halves: one half for model development and one half for model confirmation. We used a 65 deficit Frailty Index and combined 5 cognitive deficits into a global cognitive impairment index. Cross-lagged path analysis within a structural equation modelling framework was used to examine the bi-directional relationship between the two measures.

RESULTS: After controlling for age, sex, social vulnerability, education, and initial cognitive impairment, each 0.10 increase in baseline frailty was associated with a 0.01 increase in cognitive impairment at follow-up (p < 0.001). Likewise, each 0.1 increase in baseline cognitive impairment was associated with a 0.003 increase frailty at follow-up (p < 0.01).

CONCLUSION: Our findings underscore the importance of considering cognitive impairment in the context of overall health. Many people with dementia are likely to have other health problems, which need to be considered in concert to achieve optimal health outcomes.

%B J Alzheimers Dis %V 58 %P 231-242 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/28387672?dopt=Abstract %R 10.3233/JAD-161280 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Effect Size Analyses of Souvenaid in Patients with Alzheimer's Disease. %A Cummings, Jeffrey %A Scheltens, Philip %A McKeith, Ian %A Blesa, Rafael %A Harrison, John E %A Bertolucci, Paulo H F %A Rockwood, Kenneth %A Wilkinson, David %A Wijker, Wouter %A Bennett, David A %A Shah, Raj C %X

BACKGROUND: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes.

OBJECTIVE: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm.

METHODS: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer's disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes. Effect size was determined by calculating Cohen's d statistic (or Cramér's V method for nominal data), number needed to treat and number needed to harm. Statistical calculations were performed for the intent-to-treat populations.

RESULTS: In patients with mild AD, effect sizes were 0.21 (95% confidence intervals: -0.06, 0.49) for the primary outcome in Souvenir II (neuropsychological test battery memory z-score) and 0.20 (0.10, 0.34) for the co-primary outcome of Souvenir I (Wechsler memory scale delayed recall). No effect was shown on cognition in patients with mild-to-moderate AD (S-Connect). The number needed to treat (6 and 21 for Souvenir I and II, respectively) and high number needed to harm values indicate a favorable harm:benefit ratio for Souvenaid versus control in patients with mild AD.

CONCLUSIONS: The favorable safety profile and impact on outcome measures converge to corroborate the putative mode of action and demonstrate that Souvenaid can achieve clinically detectable effects in patients with early AD.

%B J Alzheimers Dis %V 55 %P 1131-1139 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27767993?dopt=Abstract %R 10.3233/JAD-160745 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Changes in Frailty Predict Changes in Cognition in Older Men: The Honolulu-Asia Aging Study. %A Armstrong, Joshua J %A Godin, Judith %A Launer, Lenore J %A White, Lon R %A Mitnitski, Arnold %A Rockwood, Kenneth %A Andrew, Melissa K %X

BACKGROUND: As cognitive decline mostly occurs in late life, where typically it co-exists with many other ailments, it is important to consider frailty in understanding cognitive change.

OBJECTIVE: Here, we examined the association of change in frailty status with cognitive trajectories in a well-studied cohort of older Japanese-American men.

METHODS: Using the prospective Honolulu-Asia Aging Study (HAAS), 2,817 men of Japanese descent were followed (aged 71-93 at baseline). Starting in 1991 with follow-up health assessments every two to three years, cognition was measured using the Cognitive Abilities Screening Instrument (CASI). For this study, health data was used to construct an accumulation of deficits frailty index (FI). Using six waves of data, multilevel growth curve analyses were constructed to examine simultaneous changes in cognition in relation to changes in FI, controlling for baseline frailty, age, education, and APOE-ɛ4 status.

RESULTS: On average, CASI scores declined by 2.0 points per year (95% confidence interval 1.9-2.1). Across six waves, each 10% within-person increase in frailty from baseline was associated with a 5.0 point reduction in CASI scores (95% confidence interval 4.7-5.2). Baseline frailty and age were associated both with lower initial CASI scores and with greater decline across the five follow-up assessments (p < 0.01).

DISCUSSION: Cognition is adversely affected by impaired health status in old age. Using a multidimensional measure of frailty, both baseline status and within-person changes in frailty were predictive of cognitive trajectories.

%B J Alzheimers Dis %V 53 %P 1003-13 %8 2016 Jun 15 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27314525?dopt=Abstract %R 10.3233/JAD-151172