Objective: To examine the association between neuropsychiatric symptoms (NPS) with self-and caregiver-rated Quality of Life (QoL) for patients with Alzheimer's disease (AD) during a 5-year follow-up. Methods: The ALSOVA 5-year follow-up study included, at baseline, 236 patients with either very mild (Clinical Dementia Rating Scale (CDR) 0.5), or mild (CDR 1) AD, together with their caregivers from three Finnish hospital districts. QoL was evaluated using patient self-reported, and caregiver-rated, QoL in AD (QoL-AD) scores. NPS were assessed using the Neuropsychiatric Inventory (NPI), and AD severity was evaluated using the CDR, with cognition tested by the mini-mental state examination. The performance of daily activities was assessed using the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Results: Over the 5-year follow-up period, patient self-reported QoL-AD scores did not change significantly (p = 0.245), despite increases in their NPS. However, caregiver-rated patient QoL-AD scores declined significantly (p ≤ 0.001), as total NPI scores increased during follow-up. No NPS at baseline, and only apathy at follow-up, correlated significantly (p = 0.007) with patient self-rated QoL-AD scores. Caregiver-rated patient QoL-AD scores correlated significantly with most NPS, especially (p ≤ 0.001) apathy, agitation, anxiety, irritability, depression, and delusions at baseline, and delusions, hallucinations, apathy, appetite disturbances, and anxiety during follow-up. Conclusions: Patient rated QoL-AD scores are an unreliable tool with which to evaluate the success of therapy for NPS. Instead, caregiver-rated scores for patients correlated well with NPI scores, and health care professionals in the clinic should preferentially use these.

This work was aimed at improving the absorption of bisphosphonates by targeting carrier systems in the intestine and the intestinal peptide carrier system (hPEPT1), in particular. (14)C-Labeled pamidronate and alendronate as well as radiolabeled and "cold" peptidyl-bisphosphonates, Pro-[(3)H]Phe-[(14)C]pamidronate, and Pro-[(3)H]Phe-[(14)C]alendronate were synthesized. In situ single-pass perfusion studies revealed competitive inhibition of transport by Pro-Phe, suggesting peptide carrier-mediated transport. Prodrug transport in the Caco-2 cell line was significantly better than that of the parent drugs, and the prodrugs exhibited high affinity to the intestinal tissue. Oral administration of the dipeptidyl prodrugs resulted in a 3-fold increase in drug absorption following oral administration in rats, and the bioavailability of Pro-Phe-alendronate was 3.3 (F(TIBIA)) and 1.9 (F(URINE)) times higher than that of the parent drug. The results indicate that the oral absorption of bisphosphonates can be improved by peptidyl prodrugs via the hPEPT1; however, other transporters may also be involved.

Background Knee osteoarthritis (OA) worsens health-related quality of life (HRQoL) but the symptom pathway varies from person to person. We aimed to identify groups of people with knee OA or at its increased risk whose HRQoL changed similarly. Our secondary aim was to evaluate if patient-related characteristics, incidence of knee replacement (KR) and prevalence of pain medication use differed between the identified HRQoL trajectory groups. Methods Eight-year follow-up data of 3053 persons with mild knee OA or at increased risk were obtained from the public Osteoarthritis Initiative (OAI) database. Group-based trajectory modeling was used to identify patterns of experiencing a decrease of ≥10 points (Minimal Important Change, MIC) in the Quality of Life subscale of the Knee injury and Osteoarthritis Outcome Score compared to baseline. Multinomial logistic regression, Cox regression and generalized estimating equation models were used to study secondary aims. Results Four HRQoL trajectory groups were identified. Persons in the ‘no change’ group (62.9%) experienced no worsening in HRQoL. ‘Rapidly’ (9.5%) and ‘slowly’ worsening (17.1%) groups displayed an increasing probability of experiencing the MIC in HRQoL. The fourth group (10.4%) had ‘improving’ HRQoL. Female gender, higher body mass index, smoking, knee pain, and lower income at baseline were associated with belonging to the ‘rapidly worsening’ group. People in ‘rapidly’ (hazard ratio (HR) 6.2, 95% confidence interval (CI) 3.6–10.7) and ‘slowly’ worsening (HR 3.4, 95% CI 2.0–5.9) groups had an increased risk of requiring knee replacement. Pain medication was more rarely used in the ‘no change’ than in the other groups. Conclusions HRQoL worsening was associated with several risk factors; surgical and pharmacological interventions were more common in the poorer HRQoL trajectory groups indicating that HRQoL does reflect the need for OA treatment. These findings may have implications for targeting interventions to specific knee OA patient groups.

Neuropsychiatric symptoms of Alzheimer’s disease (AD) such as depression may be associated with pain, which according to the literature may be inadequately recognized and managed in this population. This study aimed to identify the factors associated with analgesic use in persons with AD; in particular, how AD severity, functional status, neuropsychiatric symptoms of AD, co-morbidities and somatic symptoms are associated with analgesic use. 236 community-dwelling persons with very mild or mild AD at baseline, and their caregivers, were interviewed over five years as part of the prospective ALSOVA study. Generalized Estimating Equations (GEEs) were used to estimate unadjusted and adjusted odds ratios (ORs) for the factors associated with analgesic use over a five year follow-up. The proportion of persons with AD using any analgesic was low (13.6%) at baseline and remained relatively constant during the follow-up (15.3% at Year 5). Over time, the most prevalent analgesic changed from non-steroidal anti-inflammatories (8.1% of persons with AD at Year 1) to acetaminophen (11.1% at Year 5). Depressive symptoms (measured by the Beck Depression Inventory, BDI) were independently associated with analgesic use, after effects of age, gender, education, AD severity, comorbidities and somatic symptoms were taken into account. For every one unit increase in BDI, the odds of analgesic use increased by 4% (OR = 1.04, 95% confidence interval CI = 1.02-1.07). Caregiver depressive symptoms were not statistically significantly associated with analgesic use of the person with AD. Depressive symptoms were significantly associated with analgesic use during the five year follow-up period. Possible explanations warranting investigation are that persons with AD may express depressive symptoms as painful somatic complaints, or untreated pain may cause depressive symptoms. Greater awareness of the association between depressive symptoms and analgesic use may lead to safer and more effective prescribing for these conditions.