Biomarker profiling beyond amyloid and tau: cerebrospinal fluid markers, hippocampal atrophy, and memory change in cognitively unimpaired older adults

Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n ¼ 99, 64e93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1e42 (Ab42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain b-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Ab42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline

Factors that influence the levels of cerebrospinal fluid biomarkers in memory clinic patients

Abstract Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer’s disease. The diagnostic power of these biomarkers has been reported to vary among different studies’ results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer’s dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic. Methods We included 257 patients from two memory clinics who had been assessed for dementia, including lumbar puncture. Results The mean age of the patients was 68.1 (SD: 8.0) years; 50.2% were women and 66.5% were APOE ε4 positive. Of these patients, 80.5% were diagnosed with AD or amnestic MCI. Both APOE ε4 and increasing age were associated with decreasing levels of Aβ, but not the levels of the tau proteins. In multiple regression analyses, disease stage, defined as a MMSE ≥25 or <25, influenced factors associated with the CSF biomarkers. Among those with MMSE score ≥ 25, age, APOE ε4 genotype, and MMSE score, in addition to a diagnosis of AD, were associated with Aβ level, with an explained variance of 0.43. When using P-tau or T-tau as a dependent variable, the presence of one or two APOE ε4 alleles, and MMSE score influenced the results, in addition to the diagnosis of AD. The explained variance was lower for P-tau (0.26) and for T-tau (0.32). Among those with MMSE <25, these variables explained very little of the variance. There were no gender differences. Conclusions We found that factors in addition to a diagnosis of AD, were associated with the levels of CSF biomarkers. Among those with MMSE ≥25, lower levels of Aβ were associated with several factors including increasing age. This is not reflected in clinical practice, where age-specific cutoffs exist only for T-tau. In this study, age was not associated with the levels of tau proteins

Factors that influence the levels of cerebrospinal fluid biomarkers in memory clinic patients

Abstract Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer’s disease. The diagnostic power of these biomarkers has been reported to vary among different studies’ results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer’s dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic. Methods We included 257 patients from two memory clinics who had been assessed for dementia, including lumbar puncture. Results The mean age of the patients was 68.1 (SD: 8.0) years; 50.2% were women and 66.5% were APOE ε4 positive. Of these patients, 80.5% were diagnosed with AD or amnestic MCI. Both APOE ε4 and increasing age were associated with decreasing levels of Aβ, but not the levels of the tau proteins. In multiple regression analyses, disease stage, defined as a MMSE ≥25 or <25, influenced factors associated with the CSF biomarkers. Among those with MMSE score ≥ 25, age, APOE ε4 genotype, and MMSE score, in addition to a diagnosis of AD, were associated with Aβ level, with an explained variance of 0.43. When using P-tau or T-tau as a dependent variable, the presence of one or two APOE ε4 alleles, and MMSE score influenced the results, in addition to the diagnosis of AD. The explained variance was lower for P-tau (0.26) and for T-tau (0.32). Among those with MMSE <25, these variables explained very little of the variance. There were no gender differences. Conclusions We found that factors in addition to a diagnosis of AD, were associated with the levels of CSF biomarkers. Among those with MMSE ≥25, lower levels of Aβ were associated with several factors including increasing age. This is not reflected in clinical practice, where age-specific cutoffs exist only for T-tau. In this study, age was not associated with the levels of tau proteins

Driver diagnostics in general practitioners\u92 daily work with older patients : a Finnish-Swedish comparison of general practitioners´activities, knowledge and attitudes

I Sverige och Finland används olika metoder för att identifiera de äldre förare som av medicinska skäl inte borde fortsätta att köra bil. Svenska läkare är skyldiga att rapportera olämpliga förare, men inga medicinska undersökningar krävs för att förlänga ett körkorts giltighet. I Finland upphör körkortet att gälla vid 70 års ålder. De som önskar fortsätta köra bil måste, i samband med ansökan om ett nytt körkort, genomgå en medicinsk kontroll som omfattar det allmänna hälsotillståndet och synförmågan. Syftet med föreliggande undersökning var att jämföra finska och svenska allmänläkares aktiviteter, kunskaper och attityder beträffande åldrande och bilkörning, med avsikten att utvärdera effekterna av de bägge ländernas olika körkortspolicy. Hypotesen var att de finska allmänläkarna, p g a erfarenheten från de obligatoriska hälsokontrollerna, skulle vara bättre informerade och mera aktiva när det gäller att hantera frågan om körlämpligheten med sina äldre patienter än de svenska, som saknar denna typ av erfarenhet. Ett slumpmässigt urval av 3 000 svenska och finska allmänläkare tillfrågades i en postenkät om sina aktiviteter, kunskaper och attityder angående patienter som var aktiva förare och 65 år och däröver. Resultaten visade att den strikta finska policyn för förnyandet av körkortet för äldre förare inte medförde att allmänläkarna var bättre informerade eller mer aktiva när gällde att ta tag i körrelaterade frågor med de äldre patienterna. Skillnaderna var små mellan svenska och finska allmänläkares aktivitetsgrad och kunskapsnivå. De svenska läkarna var emellertid något mer aktiva och visste mer om demens som en riskfaktor. Icke desto mindre hade de finska läkarna en större tilltro till sin förmåga att bedöma körförmågan hos äldre patienter. Deras attityder var också mer restriktiva. Sålunda framkom inget i undersökningen som stödde hypotesen. Det finska systemet ger inte allmänläkarna bättre förutsättningar att hantera frågor om åldrande och bilkörning än de svenska allmänläkarna. Systemet kan till och med motverka sitt eget syfte genom att det hos de finska allmänläkarna skapar en illusorisk tilltro till sin förmåga att bedöma körlämpligheten.In Sweden and Finland, different methods are used for identifying elderly drivers who should not continue to drive a car for medical reasons. Although Swedish doctors are obliged to report unsuitable drivers, no medical examinations are required for extending a driving licence. In Finland, however, a driver aged 70 or over must produce a medical certificate together with a certificate of continued driving ability when renewing his licence. The main purpose of the survey was to investigate whether the Finnish system had led to doctors having greater knowledge of traffic medicine and a more active approach compared with doctors in the Swedish system, since all Finnish doctors come into contact with mandatory medical examinations for driving licences during the course of their training as well as in clinical work. A random sample of 3,000 Swedish and Finnish general practitioners was given a postal questionnaire concerning their activities, knowledge and attitudes in regard to car drivers aged 65 and over. The results showed that the differences in activity and attitudes between Swedish and Finnish doctors regarding elderly people and car driving were small. The Swedish doctors were somewhat more active, and knew more about dementia as a risk factor. The Finnish doctors, however, had greater confidence in their own capability to assess the driving ability of elderly patients. The Finnish system thus does not lead to more knowledgeable or active doctors, but can create a somewhat illusory self-confidence among doctors