Undetected dementia in community-dwelling older people: the Canadian Study of Health and Aging

OBJECTIVE: To estimate the frequency and correlates of undetected dementia in community-dwelling older people. DESIGN: Secondary analysis of data from the Canadian Study of Health and Aging (CSHA) prevalence survey of dementia. SETTING: All 10 provinces of Canada excluding Indian reserves and military units. PARTICIPANTS: A total of 252 community-dwelling older adults diagnosed with dementia in the CSHA survey. MAIN OUTCOME MEASURE: Undetected dementia, defined as occurring in persons who meet standard diagnostic criteria for dementia but who report never having seen a doctor for memory problems. RESULTS: Of the 252 subjects, 64% had undetected dementia. Subjects with mild functional impairment were significantly more likely to have undetected dementia (odds ratio = 2.4, 95% confidence interval 1.2, 5.0). Older subjects and those with mild cognitive impairment showed a trend toward undetected dementia, although the results did not achieve statistical significance. Educational level, number of comorbid conditions, and degree of social support were not significantly associated with undetected dementia. CONCLUSIONS: A large number of older persons are living in the community with undetected dementia. These older people may be at significant risk for delirium, motor vehicle accidents, medication errors, and financial difficulties. As preventive strategies are developed and new cognitive enhancing therapies emerge, we need to reexamine our current guidelines about screening for cognitive impairment in older adults.     

Mixed functional characteristics correlating with TCR‐ligand koff‐rate of MHC‐tetramer reactive T cells within the naive T‐cell repertoire

The low frequency of antigen‐specific naïve T cells has challenged numerous laboratories to develop various techniques to study the naïve T‐cell repertoire. Here, we combine the generation of naïve repertoire‐derived antigen‐specific T‐cell lines based on MHC‐tetramer staining and magnetic‐bead enrichment with in‐depth functional assessment of the isolated T cells. Cytomegalovirus (CMV) specific T‐cell lines were generated from seronegative individuals. Generated T‐cell lines consisted of a variety of immunodominant CMV‐epitope‐specific oligoclonal T‐cell populations restricted to various HLA‐molecules (HLA‐A1, A2, B7, B8, and B40), and the functional and structural avidity of the CMV‐specific T cells was studied. Although all CMV‐specific T cells were isolated based on their reactivity toward a specific peptide‐MHC complex, we observed a large variation in the functional avidity of the MHC‐tetramer positive T‐cell populations, which correlated with the structural avidity measured by the recently developed Streptamer k_off‐rate assay. Our data demonstrate that MHC‐tetramer staining is not always predictive for specific T‐cell reactivity, and challenge the sole use of MHC‐tetramers as an indication of the peripheral T‐cell repertoire, independent of the analysis of functional activity or structural avidity parameters.     

Dynamic Effects of Depressive Symptoms on Osteoarthritis Knee Pain

Objective

To estimate the dynamic causal effects of depressive symptoms on osteoarthritis (OA) knee pain.

Methods

Marginal structural models were used to examine dynamic associations between depressive symptoms and pain over 48 months among older adults (n = 2,287) with radiographic knee OA (Kellgren/Lawrence grade 2 or 3) in the Osteoarthritis Initiative. Depressive symptoms at each annual visit were assessed (threshold ≥16) using the Center for Epidemiologic Studies Depression Scale. OA knee pain was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, rescaled to range from 0 to 100.

Results

Depressive symptoms at each visit were generally not associated with greater OA knee pain at subsequent time points. Causal mean differences in WOMAC pain score comparing depressed to nondepressed patients ranged from 1.78 (95% confidence interval [95% CI] ?0.73, 4.30) to 2.58 (95% CI 0.23, 4.93) within the first and fourth years, and the depressive symptoms by time interaction were not statistically significant (P = 0.94). However, there was a statistically significant dose‐response relationship between the persistence of depressive symptoms and OA knee pain severity (P = 0.002). Causal mean differences in WOMAC pain score comparing depressed to nondepressed patients were 0.89 (95% CI ?0.17, 1.96) for 1 visit with depressive symptoms, 2.35 (95% CI 0.64, 4.06) for 2 visits with depressive symptoms, and 3.57 (95% CI 0.43, 6.71) for 3 visits with depressive symptoms.

Conclusion

The causal effect of depressive symptoms on OA knee pain does not change over time, but pain severity significantly increases with the persistence of depressed mood.