Christianson, Teresa J.

Abstract Objective Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain‐specific cognitive trajectories. Methods In this longitudinal study conducted in the setting of the population‐based Mayo Clinic Study of Aging, 5081 community‐dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI‐Q), and Beck Depression and Anxiety Inventories (BDI‐II, BAI). Global and domain‐specific (memory, language, attention, and visuospatial skills) cognitive performance was assessed through neuropsychological testing every 15 months. Associations between baseline NPS and trajectories for individual yearly change in cognitive z‐scores were calculated using linear mixed‐effect models. Results Cognition declined regardless of NPS status over the median follow‐up of 4.5 years. Presence of NPS was associated with increased cognitive decline. Differences in annualized change in global cognition z‐scores for participants with NPS compared to without NPS ranged from −0.018 (95% CI −0.032, −0.004; p = 0.011) for irritability to −0.159 (−0.254, −0.065; p = 0.001) for hallucinations. Associations between NPS and annual decline in global cognition were significant for most NPI‐Q‐assessed NPS and clinical depression (BDI‐II≥13). Participants with NPI‐Q‐assessed depression, apathy, nighttime behavior, and clinical depression had greater decline in all domain‐specific z‐scores; presence of delusions and anxiety was associated with more pronounced decline in language, attention and visuospatial skills. Conclusion NPS were associated with a more accelerated cognitive decline. Clinical assessment and potential treatment of NPS is warranted even in a community setting as NPS may impact cognitive decline in nondemented individuals.

AbstractBackgroundPractice effects can obscure interpretation of longitudinal cognitive performance. Reliable change indices (RCIs) provide data for determining a significant change, typically for a single repeat assessment, but multiple follow‐up visits are common clinically and in research cohorts. Further, regression‐based or linear mixed effects models improve prediction of future cognitive decline and have higher correlations with neuroimaging biomarkers than RCI approaches. We present norms for change for the Auditory Verbal Learning Tests (AVLT) with conditional normative z‐scores for up to 7 repeat assessments, and demonstrate application of this method to individuals with preclinical Alzheimer’s disease (AD).MethodNormative Sample: Robust conditional norms were derived from 1001 adults ages 50‐90 from the Mayo Clinic Study of Aging (MCSA) who completed the AVLT across 4‐8 visits approximately 15 months apart and remained cognitively unimpaired (CU) across all available visits. Linear mixed effects models were used to compute a conditional normative z‐score for AVLT 30‐minute recall and sum of trials. Models included adjustment for baseline performance, number of prior test exposures, demographic factors (age, sex, education), and interactions (baseline*time; sex*time). Test Sample: We used a preclinical AD sample with positive amyloid and tau imaging (n= 27 CU A+T+; Jack et al. 2017) expected to have a higher rate of intra‐individual cognitive decline relative to CU A‐T‐ individuals (n = 268) to compare mean performances of conditional normative z‐scores to typical age‐corrected Mayo’s Older Americans Normative Studies (MOANS) norms. Participants had at least 1 and up to 4 follow‐up visits, with their most recent AT data used for classification.ResultAVLT performance based on typical norms did not differ across A+T+ and A‐T‐ groups. Specifically, across 2‐4 follow‐up visits, the typical norms mean z‐score was similar across groups (p=0.945; see Table 1). However, the conditional norms mean z‐score that accounts for practice effects and typical trajectories of AVLT performance was lower in the A+T+ relative to the A‐T‐ group for 30‐minute recall (p=0.055) and sum of trials (p=0.060).ConclusionConditional normative methods that account for practice effects are more sensitive to preclinical AD than typical norms, and show promise for identifying transitional cognitive decline.

AbstractBackgroundNeuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. However, the association between NPS and global and domain‐specific cognitive trajectories among older adults free of dementia remains unclear.MethodWe conducted a longitudinal study derived from the population‐based Mayo Clinic Study of Aging, including individuals aged ≥ 50 years who were free of dementia. Participants completed the Neuropsychiatric Inventory Questionnaire at baseline and underwent neuropsychological testing assessing four cognitive domains (i.e., memory, language, attention, visuospatial skills) every 15 months. We calculated linear mixed‐effect models with random subject‐specific intercepts and slopes to examine the association between presence of twelve different NPS (i.e., delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor behavior, nighttime behavior, appetite) at baseline and trajectories for individual yearly change in global and domain‐specific cognitive z‐scores. The models were adjusted for age, sex, education, and whether or not this was the first time the cognitive battery had been administered.ResultThe sample included 5081 persons (51% males; 4439 cognitively unimpaired, 642 with MCI). The median [IQR] age was 74 [67, 81] years, and the median [IQR] education was 14 [12, 16] years. Regardless of NPS status, participants declined in cognition over time, on average. However, presence of NPS was significantly associated with an increased decline in cognition, i.e., the annualized change in global cognition z‐scores for participants with compared to without the given NPS ranged from ‐0.018 (p = 0.011) for irritability to ‐0.16 (p = 0.001) for hallucinations. These associations between NPS and annual decline in global cognition were significant for all NPS except euphoria and disinhibition. Similar results were seen for the individual cognitive domains, e.g., participants with depression, apathy and nighttime behavior had a greater longitudinal decline in all domain specific z‐scores, whereas presence of delusions and anxiety was associated with a more pronounced decline in language, attention and visuospatial skills.ConclusionNeuropsychiatric symptoms are associated with greater longitudinal decline of both global and domain‐specific cognitive functions in community‐dwelling older adults free of dementia. More research is needed to confirm these preliminary findings.

We examined the associations between baseline neuropsychiatric symptoms (NPS) and longitudinal changes in functional performance among 5,394 non-demented individuals aged ≥50 years (2,729 males; median age 74.2 years; 4,716 cognitively unimpaired, 678 mild cognitive impairment). After adjusting for age, sex, education, and medical comorbidities, NPS assessed by the Neuropsychiatric Inventory Questionnaire, clinical depression (Beck Depression Inventory score ≥13) and anxiety (Beck Anxiety Inventory score ≥10) were significantly associated with an increase in the Functional Activities Questionnaire score, indicating functional decline over time. This association may vary depending on the degree of cognitive impairment at baseline.

Abstract If the observed dramatic increase in VTE incidence with advancing age is due to increased VTE risk factor exposure (i.e., secondary VTE), the incidence of idiopathic VTE should not vary with age or calendar year. Objective: To estimate the incidence of idiopathic and secondary VTE by age and by calendar year. Methods: Using the resources of the Rochester Epidemiology Project, we identified the inception cohort of Olmsted County, MN, residents with a first lifetime VTE during the 30-year period, 1966–1995 (n=2761). For each case, we reviewed the complete medical records in the community for 48 baseline clinical characteristics that are commonly-accepted risk factors for VTE. We categorized VTE cases as idiopathic (n=305) if no such characteristics were present; the remaining cases were categorized as secondary. Age- and sex-specific incidence rates were calculated using idiopathic or secondary VTE cases as the numerator, and age-, sex- and calendar year-specific estimates of the population of Olmsted County as the denominator. Results: The incidence of both idiopathic and secondary VTE increased exponentially with age for both men and women (p<0.001). Over the 30-year study period, the age-adjusted incidence of idiopathic VTE was essentially constant among men (from 19.0 to 17.1 per 100,000 men-years for 1966–70 and 1990–95, respectively), but decreased markedly among women (from 18.5 to 3.6 per 100,000 woman-years for 1966–70 and 1990–95, respectively; p=0.005 for the interaction). Conclusions: The dramatic increase in VTE incidence with age likely reflects the biology of aging, although as yet unidentified VTE risk factors cannot be excluded. The reason for the decreased incidence of idiopathic VTE over the last 30 years among women is unclear.

Abstract If the incidence of VTE varies by season, then the etiology of VTE could be related to seasonal exposures. However, the few studies that estimated VTE incidence by season reached conflicting conclusions. Objective: To estimate the incidence of VTE by month and by season of the year. Methods: Using the resources of the Rochester Epidemiology Project, we identified the inception cohort of Olmsted County, MN, residents with a first lifetime VTE over the 30-year period, 1966–1995 (n=2761). For each case, we reviewed the complete medical records in the community for the date of VTE onset, date of birth, gender and 48 baseline clinical characteristics commonly accepted as risk factors for VTE. We categorized cases as idiopathic (n=305) if no such characteristics were present; remaining cases were categorized as secondary. Incidence rates were calculated using the number of overall, idiopathic or secondary VTE cases by month of onset as the numerator, and age- and sex-specific estimates of the monthly population of Olmsted County as the denominator (yearly population estimates divided by 12). Results: The incidence of VTE did not vary appreciably by month of the year for overall, idiopathic or secondary VTE (all p-values >0.2). However, the overall incidence of VTE was higher in the 3 summer months (June, July, August) compared to the 3 winter months (December, January, February; 132.6 vs. 116.9 per 100,000 person-years, respectively, both age- and sex-adjusted to year 2000 U.S. Whites; p-value = 0.026). The same general pattern was true for both idiopathic and secondary VTE, but separately neither was statistically significant (p-value=0.48 and 0.15, respectively). Conclusions: The incidence of VTE is higher in the summer compared to the winter months, suggesting the hypothesis that vector-borne (e.g., mosquito, tick) and/or enteroviral infection may play a role in the etiology of VTE.