Aakre, Jeremiah A.

AbstractIntroductionWe investigated the association of the area deprivation index (ADI) with cognitive decline, mild cognitive impairment (MCI), and dementia in older adults (≥50 years old). ADI is a neighborhood socioeconomic disadvantage measure assessed at the census block group level.MethodsThe study included 4699 participants, initially without dementia, with available ADI values for 2015 and at least one study visit in 2008 through 2018. Using logistic regression and Cox proportional hazards models with age as the time scale, we assessed the odds for MCI and the risk for dementia, respectively.ResultsIn cognitively unimpaired (CU) adults at baseline, the risk for progression to dementia increased for every decile increase in the ADI state ranking (hazard ratio = 1.06, 95% confidence interval (1.01–1.11), P = .01). Higher ADI values were associated with subtly faster cognitive decline.DiscussionIn older CU adults, higher baseline neighborhood socioeconomic deprivation levels were associated with progression to dementia and slightly faster cognitive decline.Highlights The study used area deprivation index, a composite freely available neighborhood deprivation measure. Higher levels of neighborhood deprivation were associated with greater mild cognitive impairment odds. Higher neighborhood deprivation levels were associated with higher dementia risk.

AbstractBackgroundNeocortical tau can be present in over half of patients with Lewy body disease at autopsy, and may influence the timing of when a diagnosis of Dementia with Lewy bodies (DLB) can be made. We examined whether the core features, onset age and latency of probable DLB diagnosis differ by pathological subgroups.MethodAll patients (n=176) met clinical criteria for probable DLB, underwent autopsy and were classified as transitional or diffuse Lewy body disease (TLBD, DLBD). The TLBD and DLBD groups were further subdivided based on the absence of neocortical tangles represented by a low (L) Braak NFT stage of 0‐III or by the presence of neocortical tangles represented by a high (H) Braak NFT stage of IV‐VI. Onset age and latency from cognitive symptom onset to probable DLB were compared for TLBD‐L (n=30), DLBD‐L (n=47), DLBD‐H (n=78) and TLBD‐H (n=21).ResultThe TLBD‐H group met criteria for DLB at an older age (median 76 years) compared to TLBD‐L, DLBD‐L or DLBD‐H groups (median age 70 years, p<0.001). The latency to probable DLB from cognitive onset was shortest for TLBD‐L and DLBD‐L (median < 1 year), which was shorter than DLBD‐H (median 2 years; p=0.016), each of which were shorter than TLBD‐H (median 7.3 years; p<0.001). RBD was more common in men (79% men vs. 40% women, p<0.001) and in patients without neocortical tangles (86% vs. 57%, p<0.001). Patients with RBD met criteria for probable DLB at a younger age than those without a history of RBD (median 69 years vs. 76 years, p<0.001). Men had a shorter latency to probable DLB than women (median 1.0 year vs. 2.8 years, p<0.01), but this was related to RBD status that was more common in men.ConclusionPresence of RBD in both sexes led to a younger onset age and shorter latency to diagnosis of probable DLB. Patients with more widespread tau relative to α‐synuclein pathology (TLBD‐H) were older when probable DLB was diagnosed compared to those with so‐called pure Lewy body disease (TLBD‐L, DLBD‐L) or those with diffuse α‐synuclein and tau pathology (DLBD‐H).

AbstractIntroductionWe examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB).MethodsIn 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209).ResultsREM sleep behavior disorder (RBD) developed before the other core features in men and women. Men were more likely to have RBD and were diagnosed with probable DLB earlier than women. Visual hallucinations developed after the other core features in men, but in women, they appeared earlier and concurrently with fluctuations and parkinsonism. Women were older and more cognitively impaired at first visit, were less likely to have RBD, more likely to be diagnosed with probable DLB later than men, and more likely to have neocortical tangles.DiscussionAn earlier latency to probable DLB was associated with men, RBD, and Lewy body disease without neocortical tangles.

Background: The modifying effect of sex on the relation between marital status and dementia has yet to be determined. Objective: To examine if sex modifies the association between marital status and incident dementia. Methods: Population-based samples from the Mayo Clinic Study of Aging (MCSA, N = 3,471) and the Gothenburg H70 Birth Cohort Study (H70-study, N = 913) were used. A multiplicative interaction term was used to analyze the modifying effect of sex on the relation between marital status (married versus not married) and incident dementia using Cox regression models. Further, risk of dementia by marital status was also evaluated in models separated by sex. Results: In the MCSA, there was an interaction between marital status and sex in relation to dementia (p = 0.015). In contrast, in the H70-study, no significant interaction was observed (p = 0.28). Nevertheless, in both studies, not married men had increased risk of dementia compared to married men in models adjusted for age, education, and number of children (H70-study: 1.99; 1.06–3.76, MCSA: 1.43; 1.08–1.89). Associations remained similar after additional adjustment for depression, BMI, hypertension, dyslipidemia, and diabetes mellitus (H70-study: 2.00; 1.05–3.82, MCSA: 1.32; 0.99–1.76). Further, no significant association was observed between marital status and dementia in women (H70-study: 1.24; 0.82–1.89, MCSA: 0.82; 0.64–1.04). Conclusion: Sex had a modifying effect on the association between marital status and incident dementia. In analyses separated by sex, not married men had an increased risk of dementia compared to married men, while no significant association was observed between marital status and risk of dementia in women.

AbstractIntroductionThe prognostic utility of cerebrospinal fluid (CSF) phosphorylated tau 217 (p‐tau217) and p‐tau181 is not understood.MethodsAnalyses included 753 Mayo Clinic Study on Aging participants (median age = 71.6; 57% male). CSF amyloid beta (Aβ)42 and p‐tau181 were measured with Elecsys immunoassays. CSF p‐tau181 and p‐tau217 were also measured with Meso Scale Discovery (MSD). We used Cox proportional hazards models for risk of mild cognitive impairment (MCI) and linear mixed models for risk of global and domain‐specific cognitive decline and cortical thickness. Analyses were stratified by elevated brain amyloid based on CSF Aβ42 or amyloid positron emission tomography for those with imaging.ResultsCSF p‐tau217 was superior to p‐tau181 for the diagnosis of Alzheimer's disease (AD) pathology. CSF MSD p‐tau181 and p‐tau217 were associated with risk of MCI among amyloid‐positive individuals. Differences between CSF p‐tau measures predicting cortical thickness were subtle.DiscussionThere are subtle differences for CSF p‐tau217 and p‐tau181 as prognostic AD markers.

AbstractBackgroundA previous study demonstrated that cerebrospinal fluid (CSF) phosphorylated tau 217 (pTau217), compared to phosphorylated tau 181 (pTau181), correlated more strongly with Tau PET and was better able to distinguish between AD and non‐AD neurodegenerative diseases. The aim of this study was to compare these two CSF tau markers for cognitive progression.MethodWe included 666 cognitively unimpaired (CU) and 89 mild cognitive impairment (MCI) Mayo Clinic Study on Aging community‐based participants (mean age of 71.6 years) with CSF amyloid and tau measurements. CSF amyloid‐beta 42 (Aβ42) was measured with automated electrochemiluminescence Elecsys immunoassays (Roche Diagnostics); a cut‐off of <1026 pg/ml was considered amyloid positive (A+). CSF pTau181 and pTau217 were measured with the Mesoscale discovery platform (MSD). Cutoffs of pTau181≥217 pg/ml and pTau217≥288 pg/ml were considered tau positive (T+). Cox proportional hazards models with time as the time scale were used to examine the relationship between the CSF markers and progression from CU to MCI and MCI to dementia. Covariates included age, sex, education, and APOE.ResultTau positivity (T+) based on pTau217 (HR = 2.45, 95% CI: 1.45, 4.11) was a greater risk factor for incident MCI compared to pTau181 (HR = 2.07, 95% CI: 1.19, 3.61). Among individuals who were A+T+, T+ based on pTau217 (HR = 3.01, 95% CI: 1.66‐5.45) was a greater risk factor of incident MCI than pTau181 (2.80, 95% CI: 1.48, 5.31). Among the 89 MCI participants, T+ based on pTau217 was a much greater risk factor for dementia (HR = 4.92, 95% CI: 1.37, 17.61) than pTau181 (HR = 1.55, 95% CI: 0.43‐5.55).ConclusionCSF pTau217 is a better marker of cognitive progression, especially from MCI to dementia, compared to CSF pTau181.

AbstractBackgroundDementia with Lewy Bodies (DLB) is the second most common cause of degenerative dementia but the evolution of the core clinical features of DLB has not been clearly defined. The objective of this study was to identify the temporal relationship between each core feature from the estimated onset of cognitive symptoms.MethodParticipants include 485 patients with probable DLB who were evaluated at the Mayo Clinic Alzheimer Disease Research Center with neurologic and neurocognitive assessment. Each core clinical feature was compared using Kaplan‐Meier (KM) curves with the sentinel event representing age at which each core feature developed, or time from estimated cognitive onset.ResultThe sample was disproportionately male (76%). Patients were followed longitudinally, with 84% followed until death. Mean MMSE at the last evaluation was 18.3 ± 7.8. KM curves for age of onset and cumulative incidence for DLB core features as time from cognitive onset are provided. REM‐sleep behavior disorder (RBD) developed earliest and in 77% of our sample with a median KM survival estimate of 69 years (95% CI: 67.6–70.8). RBD was present in greater than 50% of patients at cognitive symptom onset. The median KM survival estimate for cognitive symptom onset was 70.2 years (95% CI: 69.3‐71.0). Parkinsonism developed in 89% with a median KM survival estimate of 73.7 years (95% CI: 72.7‐74.7). 76% had fluctuations with a similar median KM survival estimate of 74.6 years (95% CI: 73.7‐75.8). Visual hallucinations (VH) were present in 70% emerging at a median KM survival estimate of 80.2 years (95% CI: 79.5‐ 81.3). Cumulative incidence estimates for median time from cognitive onset to parkinsonism, fluctuations and VH were 2 years (95% CI: 2.0‐2.5), 2.3 years (95% CI: 2.0‐3.2) and 4.3 years (95% CI: 4.0‐4.8 years), respectively.ConclusionIn this DLB cohort, RBD was most likely to precede cognitive onset. The evolution of the other core features after cognitive onset was parkinsonism and fluctuations and then VH. While VH occur about 4 years after cognitive symptom onset, parkinsonism and fluctuations occur within the first 2 years.

Introduction: We examined the association between androgen deprivation therapy (ADT) use and the risk of mild cognitive impairment (MCI) among prostate cancer patients. Methods: We included 241 cognitively unimpaired men, aged 70 to 90, with a history of prostate cancer before enrollment in the population-based Mayo Clinic Study of Aging. Using the Rochester Epidemiology Project medical records-linkage system, ADT use and length of exposure were abstracted. Follow-up visits occurred every 15 months and MCI diagnoses were made based on clinical consensus. Cox proportional hazards models, with age as the timescale, were used to examine the association between ADT use (yes/no) and length of exposure with the risk of MCI adjusting for education, apolipoprotein E, depression, and the Charlson Index score. Results: There was no association between any ADT use (27.8% of participants) and the risk of MCI in the multivariable model [hazard ratio (HR), 1.25; 95% confidence interval (CI), 0.75-2.10]. Although not significant, there was an ADT dose-response relationship for risk of MCI: <5 years versus no use (HR, 1.08; 95% CI, 0.60-1.96) and ≥5 years versus not use (HR, 1.89; 95% CI, 0.83-4.27). Conclusion: ADT use among prostate cancer patients was not associated with an increased risk of developing MCI.