Neuropsychiatric symptoms concerning mood are common in Alzheimer's disease (AD), but it is unclear if they are etiologically related to AD pathophysiology or due to factors considered to be non-pathogenic, such as small vessel cerebrovascular disease. New generation clinical trials for AD often enroll participants with evidence of AD pathophysiology, indexed by amyloid PET scanning, but who are cognitively asymptomatic. We used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study to examine the extent to which depressive symptoms are associated with amyloid pathophysiology and small vessel cerebrovascular disease, in the form of white matter hyperintensities (WMH).

The A4 study randomizes cognitively healthy older adults with evidence of amyloid pathophysiology on PET scanning. We used screening data, which included amyloid status (positive, negative) by visual read, amyloid PET standard uptake value ratio (SUVR) in cortical regions, and MRI data acquired in a subset (n=1,197, mean age 71.6 +/- 4.8 years, 57% women) to quantitate total WMH volume. Depressive symptoms were evaluated with the 15-item Geriatric Depression Scale, which we used both as a continuous variable and to define 'depressed' and 'non-depressed' groups, based on a cut score of > 5. We examined whether 1) depressive symptoms and proportion of depressed individuals differed between amyloid positive and negative groups, 2) there is a relationship between amyloid SUVR and depressive symptoms that differs as a function of amyloid positivity status, and 3) there is a relationship between WMH volume and depressive symptoms that differs as a function of amyloid positivity status.

Although depressive symptom severity did not differ between groups (t=0.14, p=0.88), a greater proportion of individuals were classified as depressed in the amyloid negative group than the amyloid positive group (3.5% vs. 1.9%, X2=4.60, p=0.032). Increased amyloid SUVR was associated with increased GDS scores among amyloid positive individuals (r=0.117, p=0.002) but not among amyloid negative individuals (r=0.006, p=0.68, Positivity Status x SUVR interaction on GDS: ß=0.817, p=0.029). Increased WMH was associated with higher GDS scores (ß=0.105, p=0.017) but not differentially in amyloid positive and negative participants (Positivity Status x WMH interaction on GDS: ß=-0.010, p=0.243).

These analyses have several implications. First, individuals who are screened to participate in a clinical trial but do not have evidence of amyloidosis may be misattributing concerns about underlying AD pathophysiology to depressive symptoms. Second, the severity of AD pathophysiology, indexed by amyloid PET SUVR, may drive a small increase in depressive symptomatology among individuals over visual diagnostic thresholds. Third, small vessel cerebrovascular changes are additionally associated with depressive symptoms but in a manner that is independent of AD pathophysiology. Overall, depressive symptoms and depression are likely multiply determined among prospective clinical trial participants for preclinical AD.

Assess clinical and functioning treatment outcomes of risperidone long-acting injection (RLAI) versus oral antipsychotics for patients participating in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain.

e-STAR is a 2-year, multi-national, prospective, observational study of patients with schizophrenia who were initiated on RLAI or an oral antipsychotic. Data were collected retrospectively (1-year) and prospectively every three months (2 years). Outcomes included clinical effectiveness measured by Clinical Global Impression of Illness Severity (CGI-S) and patient functioning assessed by Global Assessment of Functioning (GAF) scale. Clinical and functional outcomes are analyzed using a linear mixed model controlling for age, gender, disease duration, baseline hospitalization status and antipsychotic treatment patterns. Results presented are based on the complete e-STAR data from Spain.

1,622 patients (63.6% male, mean age 38.4±11.2 years) participated in e-STAR from Spain, 1,345 were initiated on RLAI and 277 on oral antipsychotics. RLAI treated patients had significantly longer disease duration (12.6±9.5 years vs. 10.9±9.7, p<0.01) than those treated with oral antipsychotics. During the 2-year study, clinical symptoms and functioning improved in both groups. As revealed by the mixed-model regression, RLAI patients, compared to oral patients, had significantly greater improvement on CGI-S scores (-1.10 vs. -0.88, p<0.02) and GAF scores (16.4 vs. 14.6, p<0.03). Baseline hospitalization status and disease duration were significant explanatory variables in the mixed model regression.

This 2-year, prospective, observational study showed that compared to oral antipsychotics, RLAI treatment was associated with greater improvement in clinical symptoms and functioning in patients with schizophrenia.

The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice.

Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n = 1345) or a new oral antipsychotic (AP) (n = 277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review.

At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p < 0.0001) and reduction in Clinical Global Impression Severity scores (−1.14 for RLAI versus −0.94 for APs, p = 0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p < 0.05) and days (18.74 versus 13.02, p < 0.01) of hospitalizations at 24 months than oral AP patients.

This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

Evaluate impact of risperidone long-acting injection (RLAI) versus oral antipsychotics on hospitalization outcomes for patients in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain.

e-STAR is a 2-year, multi-national, prospective, observational study of patients with schizophrenia who initiated on RLAI or an oral antipsychotic. Hospitalization outcomes including number of hospitalizations and number of days in hospital were collected retrospectively (1-year) and prospectively (2 years). Changes in hospital stays and days in hospital were compared between RLAI and oral patients using linear mixed model controlling for age, gender, disease duration, and baseline antipsychotic use patterns.

1,622 patients (63.6% male, mean age 38.4±11.2 years) participated in e-STAR from Spain, 1,345 initiated on RLAI and 277 on oral antipsychotics. RLAI patients had significantly longer disease duration (12.6±9.5 years vs. 10.9±9.7 in oral patients, p<0.01). Average hospital stay at baseline was 5 days longer for RLAI than oral patients. During the study, both treatments showed reductions in mean number of hospitalizations and mean number of days in hospital. Based on the mixed-model regression, RLAI patients, compared to oral patients, had a significantly greater reduction in mean number of hospitalizations (-0.28 vs. -0.18 in followup-year1 and -0.37 vs. -0.20 in followup-year2, p<0.05) and mean number of days in hospital (-17.23 vs. -12.96 in followup-year1 and -18.75 vs. -12.99 in followup-year2, p<0.01).

This 2-year, prospective, observational study showed that compared to oral antipsychotics, RLAI treatment was associated with greater reduction in hospital stays and days in hospital in patients with schizophrenia.