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Objective: Type 2 diabetes is associated with increased risks of cognitive dysfunction and brain abnormalities. The extent to which risk factor modification can mitigate these risks is unclear. We investigated the associations between incident dementia, cognitive performance, and brain abnormalities among individuals with type 2 diabetes, according to the number of risk factors on target, compared with control subjects without diabetes.Research Design and Methods: Prospective data were from UK Biobank of 87,856 individuals (n = 10,663 diabetes, n = 77,193 control subjects; baseline 2006-2010), with dementia follow-up until February 2018. Individuals with diabetes were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking; guideline-recommended levels of glycated hemoglobin, blood pressure, BMI, albuminuria, physical activity, and diet). Outcomes were incident dementia, domain-specific cognitive performance, white matter hyperintensities, and total brain volume.Results: After a mean follow-up of 9.0 years, 147 individuals (1.4%) with diabetes and 412 control subjects (0.5%) had incident dementia. Among individuals with diabetes, excess dementia risk decreased stepwise for a higher number of risk factors on target. Compared with control subjects (incidence rate per 1,000 person-years 0.62 [95% CI 0.56; 0.68]), individuals with diabetes who had five to seven risk factors on target had no significant excess dementia risk (absolute rate difference per 1,000 person-years 0.20 [-0.11; 0.52]; hazard ratio 1.32 [0.89; 1.95]). Similarly, differences in processing speed, executive function, and brain volumes were progressively smaller for a higher number of risk factors on target. These results were replicated in the Maastricht Study.Conclusions: Among individuals with diabetes, excess dementia risk, lower cognitive performance, and brain abnormalities decreased stepwise for a higher number of risk factors on target. [ABSTRACT FROM AUTHOR]

Background: Reductions in memory practice effects have gained interest as risk factor for future cognitive decline. Practice effects vary with age and can be moderated by factors such as individual variability in arousal or stress experience acting as an additional cognitive load.Objective: In the current pilot study, we examined whether sympathetic nervous system activation moderates the relationship between age and practice effects.Methods: Thirty cognitively healthy individuals aged 40-70 years performed a mnemonic discrimination task twice. Salivary alpha amylase (sAA) samples were obtained at different time points as a proxy of sympathetic activity. Spearman correlations examined the relation between practice effects and sAA. Subsequently, age by sAA interactions on practice scores were explored with bootstrapped linear regression models. Additionally, participants were divided in learners (exhibiting practice effects) and non-learners based on the difference in mnemonic discrimination performance.Results: Higher age and baseline SNS activity were independently related to lower practice effects. The non-learners showed significantly higher sAA scores at all time points compared to learners. Among the learners, baseline-adjusted lower levels of sAA after encoding were associated with greater practice effects, particularly in middle-aged individuals. No such interaction was observed for non-learners.Conclusion: These results show that higher baseline sympathetic activation is associated with worse practice effects independently of age. Additionally, in a subgroup of middle-aged learners practice effects were observed when sympathetic activity remained low during learning. These findings suggest that elevated sympathetic nervous system activation may be a promising indicator of imminent cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have identified several subgroups (ie, latent trajectories) with distinct disease progression among people with dementia. However, the methods and results were not always consistent. This study aims to perform a coordinated analysis of latent trajectories of cognitive and functional progression in dementia across two datasets.Methods: Included and analyzed using the same statistical approach were 1628 participants with dementia from the US National Alzheimer's Coordinating Center (NACC) and 331 participants with dementia from the Dutch Clinical Course of Cognition and Comorbidity study (4C-Study). Trajectories of cognition and instrumental activities of daily living (IADL) were modeled jointly in a parallel-process growth mixture model.Results: Cognition and IADL tended to decline in unison across the two samples. Slow decline in both domains was observed in 26% of the US sample and 74% of the Dutch sample. Rapid decline in cognition and IADL was observed in 7% of the US sample and 26% of the Dutch sample. The majority (67%) of the US sample showed moderate cognitive decline and rapid IADL decline.Conclusions: Trajectories of slow and rapid dementia progression were identified in both samples. Despite using the same statistical methods, the number of latent trajectories was not replicated and the relative class sizes differed considerably across datasets. These results call for careful consideration when comparing progression estimates in the literature. In addition, the observed discrepancy between cognitive and functional decline stresses the need to monitor dementia progression across multiple domains. [ABSTRACT FROM AUTHOR]

Background: Differences in dementia risk across the gradient of socioeconomic status (SES) exist, but their determinants are not well understood.Objective: This study investigates whether health conditions and lifestyle-related risk factors explain the SES inequalities in dementia risk.Methods: 6,346 participants from the English Longitudinal Study of Ageing were followed up from 2008/2009 until 2014/2015. We used Cox regression adjusted for age, gender, wealth/education, and clustering at the household level to examine the association between SES markers (wealth, education) and time to dementia in a structural equation model including potential mediation or effect modification by a weighted compound score of twelve modifiable risk and protective factors for dementia ('LIfestyle for BRAin health' (LIBRA) score).Results: During a median follow-up of 6 years, 192 individuals (3.0%) developed dementia. LIBRA scores decreased with increasing wealth and higher educational level. A one-point increase in the LIBRA score was associated with a 13% increase in dementia risk (hazard ratio (HR) = 1.13, 95% confidence interval 1.07-1.19). Higher wealth was associated with a decreased dementia risk (HR = 0.58, 0.39-0.85). Mediation analysis showed that 52% of the risk difference between the highest and lowest wealth tertile was mediated by differences in LIBRA (indirect effect: HR = 0.75, 0.66-0.85). Education was not directly associated with dementia (HR = 1.05, 0.69-1.59), but was a distal risk factor for dementia by explaining differences in wealth and LIBRA scores (indirect effect high education: HR = 0.92, 0.88-0.95).Conclusion: Socioeconomic differences in dementia risk can be partly explained by differences in modifiable health conditions and lifestyle factors. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether self- and proxy-reported cognitive decline in older adults reflect an actual objective cognitive dysfunction in the clinical sense, and if these are predictive for developing dementia.Objective: The aim of the present study is to investigate the cross-sectional and longitudinal relation between subjective cognitive decline and objective cognitive performance, depressive symptoms, and to determine the predictive value for development of dementia.Methods: We included 405 patients without dementia at first visit from the Maastricht memory clinic participating in a longitudinal cohort study. Subjective cognitive decline was measured using a self- and proxy-report questionnaire. All patients underwent a standardized neuropsychological assessment. Follow-up assessments were performed yearly for three consecutive years, and once after five years.Results: Subjective cognitive decline was associated with lower cognitive performance and more depressive symptoms. When comparing self- (n = 342, 84%) and proxy-reported decline (n = 110, 27%), it was shown that proxy reports were associated with a more widespread pattern of lower cognitive performance. In participants without cognitive impairment proxy-reported decline was not associated with depressive symptoms. In contrast, self-reported decline was associated with a stable course of depressive symptoms at follow-up. Proxy-reported cognitive decline (HR = 1.76, 95% CI = 1.12- 2.78), and mutual complaints (HR = 1.73, CI:1.09- 2.76) predicted incident dementia while self-reported decline did not reach statistical significance (HR = 1.26, 95% CI = 0.65- 2.43).Conclusion: Proxy-reported cognitive decline was consistently associated with lower cognitive performance and conversion to dementia over 5 years. Self-reported cognitive decline in patients without cognitive impairment might indicate underlying depressive symptoms and thus deserve clinical attention as well. [ABSTRACT FROM AUTHOR]

Measures of amyloid-β (Aβ) and phosphorylated tau (p-tau) concentrations in cerebrospinal fluid are extensively used for diagnostic and research purposes in Alzheimer's disease (AD) as correlates of cortical thinning and cognitive outcomes. The present study investigated the relationship of Aβ and p-tau with hippocampal subfield volumes Cornu Ammonis (CA) 1-4, dentate gyrus (DG), and subiculum. Subfields were segmented from T1-weighted images from the ADNI-population using FreeSurfer v6. Linear and polynomial regression models revealed distinct associations of Aβ and p-tau with subfield volumes. Aβ had a quadratic relationship with all hippocampal subfield volumes and the inflection point was higher than the validated cut-off for Aβ. For p-tau the relationships were linear, except for CA3, in which it was quadratic. For the CA1 and CA3, these quadratic relationships with Aβ were only observed when p-tau was low. Amyloid and p-tau contributed equally to the explained variance in CA4 and DG volume. Subicular volume was best explained by Aβ alone. These biomarker relationships with hippocampal subfield volumes seem to mirror the hippocampal-specific topography of Aβ and tau reported in neuropathological staging models. In addition, using continuous values of Aβ reveals positive patterns with imaging markers for individuals around the positivity threshold that would be masked when using dichotomized biomarker groups, which can be important for early detection and accurate inclusion of potential participants at risk for AD in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Promoting adaptation, improving well-being and maintaining an optimal quality of life (QOL) is an important aspect in dementia care. The purpose of this study was to identify determinants of QOL in young onset dementia, and to assess differences in QoL domains between people with Alzheimer's disease (AD) and frontotemporal dementia (FTD). Methods: In total 135 persons with AD and 58 persons with FTD were included from two prospective cohort studies. QOL was assessed with the proxy reported quality of life in Alzheimer's disease questionnaire (QoL-AD). Possible determinants were explored using multiple linear regression and included sociodemographic variables, diagnosis, dementia severity, disease awareness, neuropsychiatric symptoms, met and unmet needs and hours of personal and instrumental care. Differences between QOL domains in people with AD and FTD were calculated using Mann-Whitney U tests. Results: Lower QOL was associated with more depressive symptoms, lower disease awareness, and a higher amount of needs, both met and unmet. People with AD scored lower on the memory and higher on the friends' subscale. No differences were found for the other items. Conclusion: This study demonstrates a unique set of determinants of QOL in AD and FTD. Interventions directed towards these specific factors may improve QOL. [ABSTRACT FROM AUTHOR]

Background/Aims: Knowledge about neuropsychiatric symptoms in young-onset Alzheimer's disease (YO-AD) is scarce, but essential to establish a prognosis and plan care for YO-AD patients. The aim of this study is to assess frequency parameters of neuropsychiatric symptoms in YO-AD over 2 years and investigate whether there are differences compared with late-onset Alzheimer's disease (LO-AD). Methods: 98 YO-AD and 123 LO-AD patients and caregivers from two prospective cohort studies were included and assessed every 6 months for 2 years, using the Neuropsychiatric Inventory to evaluate neuropsychiatric symptoms. Results: Over the course of 2 years, the incidence, prevalence and persistence of neuropsychiatric symptoms were in general lower in YO-AD than in LO-AD, specifically for delusions, agitation, depression, anxiety, apathy, irritability and aberrant motor behavior. Frequency of individual symptoms showed large variability in both groups. Within the group of YO-AD patients, apathy was the most prevalent symptom. Conclusion: Neuropsychiatric symptoms, notably apathy, should be paid appropriate attention to in the diagnosis and treatment of YO-AD patients. Further research is needed to gain insight into the mechanisms underlying the differences in neuropsychiatric symptoms between YO-AD and LO-AD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Data on the prevalence and clinical value of primitive reflexes (PRs) in dementia are controversial, mainly due to a lack of standardization of the methods by which these signs are elicited and scored. A standardized protocol was used to investigate eight PRs in 20 patients with Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 20 control subjects for each group. Both patient groups showed considerably more PRs than the control groups. The prevalence of PRs was related to the severity of dementia. No single reflex or combination of PR pathognomonic for dementia could be distinguished. The PR profile of AD and VD patients were similar. [ABSTRACT FROM PUBLISHER]

Objectives With the lack of a cure for Alzheimer disease (AD), the identification of comorbidity is important to reduce the possibility of excess disability. Although comorbidity in patients with late-onset AD (LO-AD) is common, for people with young-onset AD (YO-AD), it is unclear how often comorbidity occurs. Furthermore, it is uncertain whether comorbidity in patients with YO-AD differs from that in patients with LO-AD. The aim of this study was to explore the prevalence, types of morbidity, and morbidity profiles in patients with YO-AD compared with those of patients with LO-AD. Design Explorative cohort study from 2 separate Dutch cohorts (Needs in Young-onset Dementia [NeedYD] and the Clinical Course of Cognition and Comorbidity–Dementia Study [4C-Dementia study]). Setting Participants were recruited in 2007 and 2008 from (1) the memory clinics of 3 Dutch Alzheimer centers, (2) the memory clinics of general hospitals, (3) mental health services in the southern part of the Netherlands, and (4) young-onset dementia specialized day care facilities. A comparison group of community-dwelling, elderly patients with AD was selected from the 4C-Dementia study. Patients in this study were recruited in 2010 and 2011 from the aforementioned Alzheimer centers. Measurements The prevalence rates of comorbidity were compared between 177 patients with YO-AD and 155 patients with LO-AD. Comorbidity was classified using the International Classification of Diseases, 10th Revision (ICD-10). The total amount of comorbidity was established by counting the number of existing diseases (ICD categories or chapters) and comorbidity was also dichotomized as present or absent. Furthermore, a hierarchical cluster analysis was performed to study clusters of comorbidity. Results Compared with LO-AD, patients with YO-AD showed less ( P < .001) overall comorbidity (58.2% vs 86.5%) and had lower prevalence rates of diabetes, obesity, and circulatory diseases; however, the prevalence rates of diseases of the nervous system in YO-AD (6.2%) were higher compared with those of patients with LO-AD (4.5%). The cluster analysis revealed a distinctive group of patients with YO-AD with either no comorbidity or with a disease of the nervous system. Endocrine, nutritional, and metabolic diseases and diseases of the circulatory system were present in 34% of the patients with YO-AD. Conclusion Comorbidity is less common in YO-AD than in LO-AD. However, general practitioners should be aware that approximately one-third of the patients with YO-AD suffer from or have endocrine, nutritional, and metabolic diseases and/or diseases of the circulatory system. Treatment should therefore not only focus on dementia but also on comorbidity. This attention may slow the functional decline in AD. These exploratory analyses suggested a higher prevalence of nervous system diseases in YO-AD compared with LO-AD. However, the finding did not reach statistical significance and in combination with the exploratory nature of the analyses justifies further investigation. If verified, this finding may help to decrease the time to diagnosis of AD and, subsequently, support in young patients with a neurological disease. Further investigation is needed to gain more insight into the association between comorbidity and AD in younger people. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the time from symptom onset to institutionalization in persons with young-onset dementia (YOD) and compare these findings with late-onset dementia (LOD), and to determine which factors predict institutionalization in persons with YOD compared with LOD. Design/Setting: Longitudinal study of community-dwelling patients with YOD and LOD and their caregivers. Participants: A total of 226 patients with YOD and 102 with LOD and their informal caregivers were recruited through memory clinics and health care facilities. Measurements: Cox proportional hazard models were used to relate covariates with time to institutionalization. The main outcome was time from symptom onset to institutionalization. Key predictors were cohort (YOD or LOD), neuropsychiatric symptoms, caregiver distress caused by neuropsychiatric symptoms, and caregivers’ sense of competence (Short Sense of Competence Questionnaire total score). Results: The time from symptom onset to institutionalization was nearly 9 years for patients with YOD compared with approximately 4 years for patients with LOD. In the YOD group, apathy significantly predicted time of institutionalization. Furthermore, the caregiver’s competence in caring for the person with dementia significantly predicted institutionalization in both groups. Conclusions: Patients with YOD are cared for at home for a longer period than patients with LOD. The results of this study underline the importance of a timely diagnosis for these patients and their families to facilitate the initiation of appropriate care and support. Support programs aimed at enhancing the caregivers’ sense of competence and ability to deal with neuropsychiatric symptoms, especially apathy, may postpone the institutionalization of the patient. [Copyright &y& Elsevier]