Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-ADmini randomized controlled trial.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (ßLifestyle×Time = 1.11, P = 0.038; ßLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

Evaluating the effect of rapamycin treatment in Alzheimer's disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol.

BACKGROUND: Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The "Evaluating Rapamycin Treatment in Alzheimer's Disease using Positron Emission Tomography" (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer's disease. METHODS: ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer's disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. DISCUSSION: The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer's disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06022068, date of registration 2023-08-30.

Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients.

BACKGROUND: Neuroinflammation is a hallmark of the Alzheimer's disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates. METHOD: 134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales. RESULT: Higher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales. CONCLUSION: This study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD.

CSF protein ratios with enhanced potential to reflect Alzheimer's disease pathology and neurodegeneration.

BACKGROUND: Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer's disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates. METHOD: We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins. RESULTS: The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aß42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort. CONCLUSIONS: Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.

Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia.

AIMS: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition. METHODS: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions. RESULTS: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress. CONCLUSIONS: The associations between SLEs and cognition depend on the period during which SLEs occur, but seem independent of late-life cortisol dysregulation.

Association of Sarcopenia and Its Defining Components with the Degree of Cognitive Impairment in a Memory Clinic Population.

BACKGROUND: Sarcopenia and cognitive impairment are two leading causes of disabilities. OBJECTIVE: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. METHODS: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. RESULTS: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). CONCLUSION: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients.

Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aß) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up. Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education. Results: Higher AL was associated with lower CSF Aß1-42 levels (ß = -0.175, p = 0.025), reflecting higher brain levels of Aß1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (ß = -0.030, p = 0.682) and P-tau level (ß = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years. Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.

Cortisol, cognition and Alzheimer's disease biomarkers among memory clinic patients.

Objective: This study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer's disease (AD) biomarkers in memory clinic patients. Method: Memory clinic patients were recruited from Karolinska University Hospital in Sweden (n=155). Diurnal cortisol patterns were assessed using five measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime levels (AM/PM ratio) and total daily output. Cognition was measured in five domains: memory, working memory, processing speed, perceptual reasoning and overall cognition. AD biomarkers Aß42, total tau and phosphorylated tau were assessed from cerebrospinal fluid (CSF). Cognition was measured at follow-up (average 32 months) in a subsample of participants (n=57). Results: In assessing the associations between cortisol and cognition, higher awakening cortisol levels were associated with greater processing speed at baseline. No relationship was found between diurnal cortisol patterns and change in cognition over time or CSF AD biomarkers in the total sample. After stratification by CSF Aß42 levels, higher awakening cortisol levels were associated with worse memory performance in amyloid-positive participants. In amyloid-negative participants, higher bedtime cortisol levels and a lower AM/PM ratio were associated with lower overall cognition, greater awakening cortisol levels were associated with better processing speed, and a higher AM/PM ratio was associated with better perceptual reasoning. Additionally, higher awakening cortisol levels were associated with lower CSF Aß42 levels in amyloid-positive participants, while higher bedtime cortisol levels and a lower AM/PM ratio were associated with higher CSF total tau in amyloid-negative participants. Conclusions: Our findings suggest that diurnal cortisol patterns are associated with cognitive function and provide new insights into the association between diurnal cortisol patterns and AD-related CSF biomarkers. Further research is needed to examine the complex relationship between cortisol, cognition and brain pathology.

ß-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population.

BACKGROUND AND OBJECTIVES: ATN (ß-amyloid [Aß], tau, neurodegeneration) system categorizes individuals based on their core Alzheimer disease (AD) biomarkers. An important potential future use for ATN is therapeutic decision-making in clinical practice once disease-modifying treatments (e.g., anti-amyloid), become widely available. In this cross-sectional study, we applied ATN and estimated potential eligibility for anti-amyloid treatment in a real-life memory clinic with biomarker assessments integrated into the routine diagnostic procedure and all specialized resources available for the implementation of novel treatments. METHODS: We included all consecutive patients at the Karolinska University Hospital Memory clinic in Solna, Stockholm, Sweden, who had their first diagnostic visit in April 2018-February 2021, informed consent for the clinic research database, and available clinical and biomarker (CSF and imaging) data. ATN classification was based on CSF Aß42 (or Aß42/40; A), CSF phosphorylated tau (T), and medial temporal lobe atrophy (N). For CSF markers, we applied laboratory cutoffs and data-driven cutoffs for comparison (determined with Gaussian mixture modeling). Eligibility for anti-amyloid treatment was assessed following the published recommendations for aducanumab (AD dementia or mild cognitive impairment [MCI] with no evidence of non-AD etiology, appropriate level of cognition, and AD-consistent CSF profile). RESULTS: The study population consisted of 410 patients (52% subjective cognitive impairment, 23% MCI, and 25% any dementia; age 59 ± 7 years, 56% women). Regardless of biomarker cutoffs, most patients were A-T-N- (54%-57%). A+ prevalence was 17%-30% (higher with data-driven cutoffs). Up to 13% of all patients (27% of those with MCI and 28% of those with dementia) were potentially eligible for anti-amyloid treatment when AD-consistent CSF was defined as any A+ profile. When A+T+ profile was required, treatment was targeted more to the dementia than MCI stage (eligibility up to 14% in MCI and 22% in dementia). The opposite applied to earlier-stage intervention (A+T-N-; eligibility up to 12% in MCI and 2% in dementia). DISCUSSION: In a memory clinic setting with all necessary infrastructure and national guidelines in place for dementia diagnostic examination (best-case scenario), most of the patients did not meet the eligibility criteria for anti-amyloid treatment. Continuing the development of disease-modifying treatments with different mechanisms of action is a priority.

Gait and dynamic balance in adults with spina bifida.

BACKGROUND: Spina bifida (SB) is a complex congenital malformation, often causing impaired gait performance depending on the level and extent of malformation. Research regarding gait and balance performance in adults with SB, has not been sufficiently described yet. RESEARCH QUESTION: What are the characteristics of spatiotemporal gait parameters and balance performance in adults with SB? Further, do persons with muscle function (MF) level 3 differ regarding gait and balance performance from those with MF level 1-2? METHODS: Cross-sectional observational study at an outpatient clinic. 41 adults with SB (18-65 years), who walked regularly. Spatiotemporal parameters of gait was assessed with the APDM system and balance performance with the Mini Balance Evaluation Systems Test (Mini-BESTest). Muscle strength in the legs was assessed with 0-5 manual muscle test, and participants were classified according to level of MF into groups MF1, MF2, and MF3. Two-sided t-test was used for parametric independent variables, and Cohen's d was used for effect sizes. The Mann-Whitney U test was used for non-parametric independent data and effect size was calculated by the z value (r = z/√n). RESULTS: Mean gait speed was 0.96 (SD 0.20) m/s and mean stride length 1.08 m (SD 0.17), individuals with MF3 showed significantly slower gaitspeed and shorter stride length (p < 0.05). Lumbar rotation was 21° (SD 11), and thoracic lateral sway 15° (IQR 15) with significantley difference (p < 0.001 and p < 0.05) for individuals in MF3. Mini-BESTest showed a mean score of 11.3 (SD 6.9), and individuals with MF3 showed significantly lower scores (p ≤ 0.001). SIGNIFICANCE: Gait and balance performance was reduced compared to normative data in almost all parameters, especially in persons with less muscle function. Increased knowledge from advanced gait analysis may help healthcare professionals to design rehabilitation programmes, in order to achieve and maintain a sustainable gait and balance performance.

The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors.

BACKGROUND: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. METHODS: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. RESULTS: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. CONCLUSION: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

Adults with spina bifida: ambulatory performance and cognitive capacity in relation to muscle function.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Describe and compare ambulatory performance and cognitive capacity in relation to muscle function in an adult cohort with spina bifida. Also, explore factors associated with ambulation in participants with muscle function level 3. SETTING: Specialist clinic for adults with spinal cord disorders in Stockholm, Sweden. METHODS: A total regional cohort of adults (n = 219) with spina bifida was invited, 196 (104 women, mean age 35 years, SD 13 years) participated. Mode of mobility, cognitive capacity and muscle function were investigated. For participants with muscle function level 3, factors associated with ambulation were investigated using multivariate logistic regression analysis. RESULTS: In all, 84 participants (42%) were community ambulators, 22 (12%) household ambulators and 90 (46%) wheelchair users. There was a linear association between the lower degree of muscle function and scoliosis (P < 0.001). Mode of mobility varied despite similar muscle prerequisites in participants with muscle function level 3 (n = 58). Factors associated with ambulation in participants with muscle function level 3 were the absence of scoliosis, lower BMI and higher cognitive capacity. CONCLUSIONS: Cognitive capacity and mode of mobility varied widely across the cohort. However, in participants with muscle function level 3, despite similar muscular prerequisites, a large variation in the mode of mobility was found, suggesting that other factors were involved. It is important to prevent scoliosis, support a healthy lifestyle, as well as offer cognitive screening and support to promote ambulatory function and optimise independence in the everyday lives of adults with spina bifida.

Cognitive function and performance of everyday activities in adults with spina bifida.

BACKGROUND AND OBJECTIVE: Individuals with spina bifida often have cognitive impairments leading to dif-ficulties in education and daily activities. The aims of this study were to explore cognitive impairments in adults with spina bifida and to consider associations between impairments, educational outcome and per-formance of daily activities, comparing individuals with and without intellectual disability. METHODS: Data were collected on 35 adults with spina bifida via cognitive tests and Assessment of Motor and Process Skills (AMPS). Participants were divided into 3 groups: individuals without intellectual disability who completed compulsory education (NID-C); those without intellectual disability, who failed to successfully pass compulsory education (NID-F); and those with intellectual disability failed to successfully pass compulsory education (ID-F). RESULTS: All individuals with intellectual disability failed to successfully pass compulsory education (group ID-F) and had poorer scores across almost all measures than group NID-F and significantly poorer scores than group NID-C. All except 6 individuals scored below cut-off levels for effort and safety on both AMPS motor and process scales; more significant associations were seen between the cognitive tests and the motor rather than process scale. CONCLUSION: Cognitive impairments, irrespective of intellectual disability, impact on the performance of eve-ryday activities and on educational achievement, and thus need to be considered in assessments and inter-ventions to improve outcomes and promote independence in people with spina bifida.

The Executive Checklist (EC-10) - a new rating instrument for clinicians assessing dysexecutive behavior.

Assessment of executive functions (EF) is often criticized for its lack of ecological validity. As a consequence, several self- and partner rating scales for EF have been developed, while rating scales designed for clinicians are lacking. We therefore developed the Executive Checklist (EC-10), a new rating scale for clinicians assessing dysexecutive behavior during neuropsychological assessment and examined its psychometric properties. Consecutive referrals from a memory clinic with subjective cognitive impairment (SCI; n = 27), mild cognitive impairment (MCI; n = 29), dementia (DEM; n = 16), as well as 11 healthy controls were assessed with the EC-10 while performing common neuropsychological tests. Results showed that the EC-10 had excellent inter-rater reliability, good internal consistency and modest relations to cognitive laboratory measures. The EC-10 increased the classification rate above and beyond the influence of neuropsychological tests when comparing patients with SCI and MCI or between cognitively impaired and non-impaired patients. Conclusively, the present study demonstrates that clinical observations can be quantified using the EC-10 and that this rating provides valuable information. As executive deficits are common in many neurological and neuropsychiatric disorders, validating the EC-10 in broader patient groups should be an important avenue for future research.

Cognitive challenges in persons with spina bifida: Bearing on urological dysfunctions?

AIM: To evaluate if adult persons with spina bifida (SB) who have urinary tract complications have cognitive difficulties that can be identified by neuropsychological tests. METHODS: All individuals with SB ≥ 18 years of age registered at a regional outpatient clinic (n = 219) were invited, of which, 154 persons were included. Neuropsychological assessment of their cognitive status was performed with Wechsler Adult Intelligence Scale®-Fourth Edition: Coding, Block design, Arithmetic's, FAS (word generation), Rey Auditory Verbal Test for learning, and delayed recall 30 min. Bladder and bowel function were assessed with questions used by the Nordic Spinal Cord Injury Registry (NSCIR) in structured interviews, by questionnaires, and by chart reviews. RESULTS: Average neuropsychological test results for this SB population was shown to be approximately 1 SD under the median for the general population. The Coding test showed significantly lower test results as compared with the whole SB group in persons with urinary tract complications, especially urinary tract infections, reduced kidney function, dependent emptying of the bladder, and the bowel and accidental bowel leakage. The Arithmetic's test showed a significant difference between subgroups in all parameters except reduced kidney function whereas the other neuropsychological tests were significantly correlated with some but not all urological parameters. CONCLUSION: We propose neuropsychological testing with primarily two tests to find those persons with SB who, due to cognitive challenges, might need extra support to minimize urological complications.

Adults with spina bifida: A cross-sectional study of health issues and living conditions.

OBJECTIVE: To describe health issues and living conditions in a cohort of adults living with Spina bifida. MATERIAL AND METHODS: A cross-sectional study was conducted by a multidisciplinary team. Adults with spina bifida (n = 219) were invited to participate. One-hundred-and-ninety-six persons (104 women and 92 men; 18-73 years, median age 33 years) were included. Structured interviews, questionnaires, and clinical assessments for medical, social, physical, and cognitive functions were used. RESULTS: There was large variation among participants as regards the consequences of their spina bifida. Individuals < 46 years seemed to have more secondary conditions such as hydrocephalus, Chiari II malformation, tethered cord symptoms, and latex allergy. A higher proportion of the individuals >46 years and older was able to walk, and they had performed better in primary school and on tests of psychomotor speed and executive function. CONCLUSIONS: This study demonstrates that adults with spina bifida have a complex set of physical, cognitive, and social needs that need to be addressed in order to improve their health issues and living conditions. The high prevalence of urinary and fecal incontinence, pain, and overweight underline that these issues need much attention during follow-up. The future generations of older adults may need more attention in many ways, since they at a younger age do have more complex medical conditions, lower physical and cognitive functions, and lower prerequisites for independent living and participation in society than those > 46 years today. This elucidates that adults with spina bifida need systematic follow-up services and social support throughout life.

Progression to dementia in memory clinic patients with mild cognitive impairment and normal ß-amyloid.

BACKGROUND: Determination of ß-amyloid (Aß) positivity and likelihood of underlying Alzheimer's disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aß within the normal range may still have a substantial risk of developing dementia, primarily of Alzheimer type. Their prognosis, as well as predictors of clinical progression, are not fully understood. The aim of this study was to explore the associations of cerebrospinal fluid (CSF) biomarkers (Aß42, total tau, phosphorylated tau) and other characteristics, including modifiable vascular factors, with the risk of progression to dementia among patients with MCI and normal CSF Aß42. METHODS: Three hundred eighteen memory clinic patients with CSF and clinical data, and at least 1-year follow-up, were included. Patients had normal CSF Aß42 levels based on clinical cut-offs. Cox proportional hazard models with age as time scale and adjusted for sex, education, and cognition (Mini-Mental State Examination) were used to investigate predictors of progression to dementia and Alzheimer-type dementia. Potential predictors included CSF biomarkers, cognitive performance (verbal learning and memory), apolipoprotein E (APOE) ε4 genotype, medial temporal lobe atrophy, family history of dementia, depressive symptoms, and vascular factors, including the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score. Predictive performance of patient characteristics was further explored with Harrell C statistic. RESULTS: Lower normal Aß42 and higher total tau and phosphorylated tau were associated with higher dementia risk, and the association was not driven by Aß42 values close to cut-off. Additional predictors included poorer cognition, APOE ε4 genotype, higher systolic blood pressure, and lower body mass index, but not the CAIDE dementia risk score. Aß42 individually and in combination with other CSF biomarkers improved the risk prediction compared to age and cognition alone. Medial temporal lobe atrophy or vascular factors did not increase the predictive performance. CONCLUSIONS: Possibility of underlying AD pathology and increased dementia risk should not be ruled out among MCI patients with CSF Aß42 within the normal range. While cut-offs may be useful in clinical practice to identify high-risk individuals, personalized risk prediction tools incorporating continuous biomarkers may be preferable among individuals with intermediate risk. The role of modifiable vascular factors could be explored in this context.

Lifestyle Factors and Subjective Cognitive Impairment in Patients Seeking Help at a Memory Disorder Clinic: The Role of Negative Life Events.

BACKGROUND/AIMS: A large proportion of patients at memory disorders clinics are classified as having subjective cognitive impairment (SCI). Previous research has investigated whether particular lifestyle factors known to affect cognition can be useful in differentiating patients who do not show objective evidence of memory decline. There may also exist subgroups of patients with respect to lifestyle factors that could help clinicians to understand the patient group that presents to memory clinics. These may differ in diagnostic outcome. Very little is known about potential subgroups; however, but such information may help guide interventions and potentially eliminate unnecessary diagnostic procedures. The current study investigated patterns of lifestyle-related variables, including stress, sleep, sensory sensitivity, depression, and negative life events in patients presenting to a memory disorders clinic. The aim was to determine whether subgroups existed and whether it was possible to distinguish those with objectively impaired cognition. METHODS: One hundred and seventy-eight patients (mean age 58 years) from a University Hospital Memory Disorders Clinic. RESULTS: Cluster analysis identified three groups of lifestyle-related variables. Strong determinants of clusters were negative life events and age. Patients with a high number of negative life events also tended to have highest self-reported memory complaint, higher levels of stress, depression, and sensory sensitivity. However, they did not perform the worst on memory testing. In contrast, individuals who performed the worst on memory tests were older, tended to have the least memory complaints, and less negative lifestyle factors; this group also included the highest proportion of patients with mild cognitive impairment and had the lowest median amyloid A-beta 42 (Aß42). The group with the best cognitive performance were younger, included the highest proportion of patients with SCI and the highest median Aß42. On lifestyle variables, their ratings fell in between the other groups. CONCLUSIONS: Lifestyle subgroups of patients were determined by stress, emotional problems, and age. The groups were significantly associated with Aß42 and diagnostic outcome. This pattern may confound the differentiation between objective and subjective memory problems. Asking about lifestyle variables, in conjunction with neuropsychological testing, could potentially identify individuals who are not likely to have objective memory impairment and guide interventions.

Lifestyle Factors Are Important Contributors to Subjective Memory Complaints among Patients without Objective Memory Impairment or Positive Neurochemical Biomarkers for Alzheimer's Disease.

BACKGROUND/AIMS: Many patients presenting to a memory disorders clinic for subjective memory complaints do not show objective evidence of decline on neuropsychological data, have nonpathological biomarkers for Alzheimer's disease, and do not develop a neurodegenerative disorder. Lifestyle variables, including subjective sleep problems and stress, are factors known to affect cognition. Little is known about how these factors contribute to patients' subjective sense of memory decline. Understanding how lifestyle factors are associated with the subjective sense of failing memory that causes patients to seek a formal evaluation is important both for diagnostic workup purposes and for finding appropriate interventions and treatment for these persons, who are not likely in the early stages of a neurodegenerative disease. The current study investigated specific lifestyle variables, such as sleep and stress, to characterize those patients that are unlikely to deteriorate cognitively. METHODS: Two hundred nine patients (mean age 58 years) from a university hospital memory disorders clinic were included. RESULTS: Sleep problems and having much to do distinguished those with subjective, but not objective, memory complaints and non-pathological biomarkers for Alzheimer's disease. CONCLUSIONS: Lifestyle factors including sleep and stress are useful in characterizing subjective memory complaints from objective problems. Inclusion of these variables could potentially improve health care utilization efficiency and guide interventions.