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Subjective cognitive decline is related to CSF biomarkers of AD in patients with MCI

Objective: To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD). Methods: We analyzed the multicenter baseline (cross-sectional) data of 245 patients with MCI. SCD was measured quantitatively with the Subjective Memory Decline Scale (SMDS) and qualitatively by assessing particular concerns associated with self-experienced worsening of memory. Logistic regression models were used to examine associations between SCD and abnormal CSF biomarkers, taking into account objective memory impairment, depressive symptoms, and education as covariates. Results: Abnormal CSF β-amyloid 1–42 (Aβ42) and more depressive symptoms were associated with higher SMDS scores and with the report of memory concerns. Risk of abnormal CSF Aβ42 increased by an estimated 57% for a 1-SD increase in SMDS scores and was doubled in patients who had SMDS scores >4 or who reported memory concerns, respectively. In addition, both SCD measures predicted risk of having a biomarker signature indicative of prodromal AD defined as presence of low CSF Aβ42 together with either high CSF tau or CSF phosphorylated tau 181 levels. Conclusions: In MCI, specific aspects of SCD severity and quality are related to CSF biomarkers indicative of AD. This extends findings in pre-MCI samples and calls for an improved operational assessment of SCD in MCI. This might be useful for sample enrichment strategies for increased likelihood of AD pathology.

Differential Risk of Incident Alzheimer’s Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline

BACKGROUND It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimers disease (AD) dementia. OBJECTIVE We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. METHODS We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. RESULTS Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. CONCLUSION These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Cognitive functioning in the general population: Factor structure and association with mental disorders—The neuropsychological test battery of the mental health module of the German Health Interview and Examination Survey for Adults (DEGS1‐MH)

The objective of this study is to obtain population level data about cognitive functions and their association with mental disorders. We here report factor analytic and psychometric findings of a neuropsychological test battery and examine the association of current and past mental disorders with cognitive function in a large nationwide population‐based sample of 18‐ to 79‐year‐old adults in Germany (n = 3,667) participating in the mental health module of the German Health Interview and Examination Survey for Adults 2008–2011. Confirmatory factor analysis confirmed verbal memory and executive function factors. Older age was strongly associated with lower verbal memory and executive function and with higher vocabulary scores. After adjustment for age, sex, and education, rather modest decrements were found for verbal memory (β = −.118, p = .002) and executive functions (β = −.191, p < .001) in participants with any current mental disorder (n = 442) compared to those without (n = 3,201). Small decrements in memory (β = −.064, p = .031) and executive function (β = −.111, p < .001) were found in participants with any mental disorder in the last 12 months but not in those with past (fully or partially remitted) mental disorders, compared to participants without a history of mental disorder. More fine‐grained analyses of these data will investigate the complex interplay between cognition, health behaviors, and specific mental and somatic diseases.

Prospective Associations between Single Foods, Alzheimer's Dementia and Memory Decline in the Elderly

Background: Evidence whether single “cognitive health” foods could prevent cognitive decline is limited. We investigated whether dietary intake of red wine, white wine, coffee, green tea, olive oil, fresh fish, fruits and vegetables, red meat and sausages, assessed by a single-food-questionnaire, would be associated with either incident Alzheimer’s dementia (AD) or verbal memory decline. Methods: Participants aged 75+ of the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) cohort were regularly followed over 10 years (n = 2622; n = 418 incident AD cases). Multivariable-adjusted joint modeling of repeated-measures and survival analysis was used, taking gender and Apolipoprotein E4 (APOE ε4) genotype into account as possible effect modifiers. Results: Only higher red wine intake was associated with a lower incidence of AD (HR = 0.92; P = 0.045). Interestingly, this was true only for men (HR = 0.82; P < 0.001), while in women higher red wine intake was associated with a higher incidence of AD (HR = 1.15; P = 0.044), and higher white wine intake with a more pronounced memory decline over time (HR = −0.13; P = 0.052). Conclusion: We found no evidence for these single foods to be protective against cognitive decline, with the exception of red wine, which reduced the risk for AD only in men. Women could be more susceptible to detrimental effects of alcohol.

Advance directives for future dementia can be modified by a brief video presentation on dementia care: An experimental study

Objectives To investigate whether life-sustaining measures in medical emergency situations are less accepted for an anticipated own future of living with dementia, and to test whether a resource-oriented, in contrast to a deficit-oriented video about the same demented person, would increase the acceptance of such life-saving measures. Design Experimental study conducted between September 2012 and February 2013. Setting Community dwelling female volunteers living in the region of Bonn, Germany. Participants 278 women aged 19 to 89 (mean age 53.4 years). Intervention Presentation of a video on dementia care focusing either on the deficits of a demented woman (negative framing), or focusing on the remaining resources (positive framing) of the same patient. Main outcome measures Approval of life-sustaining treatments in five critical medical scenarios under the assumption of having comorbid dementia, before and after the presentation of the brief videos on care. Results At baseline, the acceptance of life-sustaining measures in critical medical situations was significantly lower in subjects anticipating their own future life with dementia. Participants watching the resource-oriented film on living with dementia had significantly higher post-film acceptance rates compared to those watching the deficit-oriented negatively framed film. This effect particularly emerges if brief and efficient life-saving interventions with a high likelihood of physical recovery are available (eg, antibiotic treatment for pneumonia). Conclusions Anticipated decisions regarding life-sustaining measures are negatively influenced by the subjective imagination of living with dementia, which might be shaped by common, unquestioned stereotypes. This bias can be reduced by providing audio-visual information on living with dementia which is not only centred around cognitive and functional losses but also focuses on remaining resources and the apparent quality of life. This is particularly true if the medical threat can be treated efficiently. These findings have implications for the practice of formulating, revising, and supporting advance directives.

What Is Successful Aging? A Psychometric Validation Study of Different Construct Definitions

Background and Objectives We examined the validity of 5 successful aging (SA) operationalizations that assessed different facets of the SA construct (cognitive and physical health and disability; well-being; social engagement). Research Design and Methods A total of 2,478 participants (mean age = 82.5 years, standard deviation [SD] = 3.47) were studied. We used confirmatory factor analysis to investigate the relationships between facets and to determine the convergent validity as well as short-term (1.5 years) and long-term (4.5 years) predictive validity of the 5 SA operationalizations for measures of quality of life (QoL) and objective health outcomes. Results A general SA operationalization that included all SA facets but also allowed differences between them showed the best model fit and construct validity. A biomedical operationalization of SA that excluded either the well-being or the social engagement facet showed lower convergent and predictive validity for subjective measures (e.g., QoL) but higher associations with objective measures (e.g., health). A purely psychosocial SA operationalization that excluded the physiological facet did not allow good prediction of objective health outcomes. Discussion and Implications Our results suggest that a well-balanced SA operationalization should include measures assessing health, disability, well-being, and social engagement.

Prevalence of pain and its associated factors among the oldest-olds in different care settings – results of the AgeQualiDe study

BackgroundThe prevalence of pain is very common in the oldest age group. Managing pain successfully is a key topic in primary care, especially within the ageing population. Different care settings might have an impact on the prevalence of pain and everyday life.MethodsParticipants from the German longitudinal cohort study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) were asked to rate their severity of pain as well as the impairment with daily activities. Besides gender, age, education, BMI and use of analgesics we focused on the current housing situation and on cognitive state. Associations of the dependent measures were tested using four ordinal logistic regression models. Model 1 and 4 consisted of the overall sample, model 2 and 3 were divided according to no cognitive impairment (NCI) and mild cognitive impairment (MCI).ResultsResults show a decline in pain at very old age but nonetheless a high prevalence among the 85+ year olds. Sixty-three per cent of the participants report mild to severe pain and 69% of the participants mild to extreme impairment due to pain with daily activities. Use of analgesics, depression and living at home with care support are significantly associated with higher and male gender with lower pain ratings.ConclusionsSufficient pain management among the oldest age group is inevitable. Outpatient care settings are at risk of overlooking pain. Therefore focus should be set on pain management in these settings.

APOE-ε4 MODULATES LEVELS OF OMEGA-3 AND OMEGA-6 FATTY ACIDS IN ALZHEIMER’S DISEASE DEMENTIA

a clinical diagnosis of Alzheimer’s’ disease (AD). Here, we report on the data we obtained in a larger cohort of patients with clinically diagnosed AD or Frontotemporal Dementia (FTD). Methods: The Belgian cohorts comprised 1289 AD and 286 FTD patients, the control cohort 809 individuals. Targeted parallel sequencing of a multi-gene panel of the major dementia genes was used, to detect rare coding variants. Results:A total of 106 rare mutations (MAF <1%) was observed in 244 individuals, including 20 known pathogenic mutations in APP, PSEN1, GRN, MAPT, VCP and TARDBP in 26 patients (1.65%) and 1 control person (0.12%). Furthermore, we detected 30 rare VUS, absent from any mutation database, in 32 patients and 7 control individuals. Among these VUS, we observed a novel frameshift mutation in PSEN2 p.K82Ifs*42, in an FTD patient with pathologically confirmed Pick’s disease. Subsequent cDNA sequencing revealed the presence of the mutated transcript. We also identified a compound heterozygous patient, carrying the 2 mutations, p.P49L and p.G183V, in PSEN1. The patient was clinically diagnosed with AD, which was pathologically confirmed. Conclusions:Genetic screening of dementia genes in Belgian AD and FTD patient cohorts identified a novel PSEN2 frameshift mutation in a FTD patient, and compound heterozygous PSEN1mutations in a familial AD patient. Together with our previous findings, these findings underline the possibility of other rare genetic events contributing to neurodegenerative dementia.

A GENERIC LATENT VARIABLE APPROACH FOR MEASURING COGNITIVE RESERVE: PHENOTYPE VALIDATION AND GENETIC ASSOCIATION RESULTS

Cleveland, OH, USA; Harvard T.H. Chan School of Public Health, Boston, MA, USA; University of Washington, Seattle, WA, USA; National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA; National Institute on Aging/National Institutes of Health (NIA/NIH), Baltimore, MD, USA; Stanford University, Palo Alto, CA, USA; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€olndal, Sweden; Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Memory Clinic, Sk ane University Hospital, Malm€o, Sweden; Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Vanderbilt University, Nashville, TN, USA; Icahn School of Medicine at Mount Sinai, New York, NY, USA; Rush University Medical Center, Chicago, IL, USA. Contact e-mail: logan.c. dumitrescu@vanderbilt.edu

Computer-assisted prediction of clinical progression in the earliest stages of AD

Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression.