Cognitive impairment in people with physical frailty using the phenotype model: A systematic review and meta analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to study the relationship between cognitive functioning and phenotypic frailty status. METHODS: We searched Pubmed, Cochrane Library and Epistemonikos from 2000 until March 2022, and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Samples included both sexes, age ≥55 years, assessed with standardized measures of the different cognitive domains and the frailty phenotype model and analyzing the relationship between the frailty subtypes pre-frail, frail and robust and specific cognitive function. RESULTS: Eleven studies published from 2008 until March 2022 fulfilled the inclusion criteria, and 10 were included in our meta-analyses. Sample sizes varied from 104 to 4649 individuals. Mean Mini-Mental State Examination (MMSE) scores ranged from 17.0 to 27.6, with mean difference (MD) of -2.55 (95% confidence interval [CI] -3.32, -1.78) in frail compared to robust, MD -1.64 (95% CI -2.21, -1.06) in frail compared to prefrail and MD -0.68 (95% CI -0.94, -0.43) in prefrail compared to robust. In subgroup analyses, frail persons had lower scores in the memory domain with standardized mean difference (SMD) -1.01 (95% CI -1.42, -0.59). CONCLUSION: MMSE scores were significantly lower in frail compared to robust and prefrail persons and in prefrail compared to robust persons. Subgroup analysis of memory revealed significantly poorer scores in frail compared to robust. The results indicate a strong relationship between physical frailty and cognitive impairment suggesting incorporation of cognitive function in frailty assessments.

Carotid Atherosclerosis and Longitudinal Changes of MRI Visual Rating Measures in Stroke Survivors: A Seven-Year Follow-Up Study.

OBJECTIVES: We aimed to assess longitudinal changes in MRI measures of brain atrophy and white matter lesions in stroke and transient ischemic attack (TIA) survivors, and explore whether carotid stenosis predicts progression of these changes, assessed by visual rating scales. MATERIALS AND METHODS: All patients with a first-ever stroke or TIA admitted to Bærum Hospital, Norway, in 2007/2008, were invited in the acute phase and followed for seven years. Carotid ultrasound was performed during the hospital stay. Carotid stenosis was defined as ≥50% narrowing of lumen. MRI was performed one and seven years after the index event and analyzed according to the visual rating scales Fazekas scale (0-3), Medial Temporal Lobe Atrophy (MTLA) (0-4) score, and Global Cortical Atrophy (GCA) scale (0-3). Patients with MRI scans at both time points were included in this sub-study. RESULTS: Of 227 patients recruited, 76 had both MRI examinations. Mean age 73.9±10.6, 41% women, and 9% had ≥50% carotid stenosis. Mean Fazekas scale was 1.7±0.9 and 1.8±1.0, mean MTLA score 1.0 ±1.0 and 1.7±1.0, and mean GCA scale score 1.4±0.7 and 1.4±0.6 after one and seven years, respectively. 71% retained the same Fazekas scale score, while 21% showed progression. Deterioration in GCA scale was seen in 20% and increasing MTLA score in 57%. Carotid stenosis was not associated with progression on Fazekas score, MTLA score or GCA scale. CONCLUSIONS: Three out of five showed progression on the MTLA score. Carotid stenosis was not associated with longitudinal change of visual rating scales.

Alzheimer's disease ­ diagnosis and treatment. / Alzheimers sykdom ­ diagnostikk og behandling.

Alzheimer's disease is the most common cause of dementia globally. Its prevalence will increase considerably in the years to come, in pace with the increasing proportion of older people. No disease-modifying treatment is currently available. Measures to mitigate risk in mid-life may potentially prevent or postpone up to 40 % of dementia cases at group level.

No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study.

BACKGROUND: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-ß peptide (Aß42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke. METHODS: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aß42 levels were assessed using linear regression. RESULTS: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aß42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort. CONCLUSIONS: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

Predictors for Favorable Cognitive Outcome Post-Stroke: A-Seven-Year Follow-Up Study.

BACKGROUND AND PURPOSE: Knowledge of the burden and development of post-stroke cognitive impairments (CIs) in the long-term after the first event is limited. We aimed to assess the prevalence of mild CI (MCI) and dementia 7 years after first-ever stroke or transient ischemic attack (TIA), to subclassify the impairments, and to identify predictors for a favorable cognitive outcome. MATERIALS AND METHODS: During 2007 and 2008, 208 patients with first-ever stroke or TIA without preexisting CI were included. After 1 and 7 years, survivors were invited to a follow-up. Transitions of cognitive status from 1 to 7 years were recorded based on the 3 categories dementia, MCI, or none. Etiologic subclassification was based on clinical cognitive profile, magnetic resonance imaging (MRI) findings, and biomarkers at both time points. Favorable outcome was defined as normal cognitive function or MCI after 7 years with exclusion of those who had progression from normal to MCI. RESULTS: Eighty patients died during follow-up, 12 patients refused further participation. After 7 years, 109 completed follow-up of whom 40 (37%) were diagnosed with MCI and 24 (22%) with dementia. Of the 64 patients diagnosed with CI, 9 were subclassified with degenerative cognitive disease, 13 with vascular disease, and 42 had mixed cognitive disease. In all, 65 patients (60%) had a favorable outcome. In multivariable logistic regression analysis, lower age and lower medial temporal lobe atrophy (MTLA) grade on MRI at 12 months were independently associated with a favorable outcome, adjusted OR (95% CI), 0.94 (0.86-0.92), and 0.55 (0.35-0.85), respectively. CONCLUSIONS: Sixty percent of stroke survivors have a favorable cognitive outcome. Lower age and lower MTLA grade on MRI were associated with favorable outcome.

Effect on anxiety and depression of a multifactorial risk factor intervention program after stroke and TIA: a randomized controlled trial.

OBJECTIVES: Depression and anxiety related to stroke are caused by vascular lesions and psychological reactions. Treatment of vascular and modifiable behavioral risk factors reduces the risk of stroke and may also reduce the risk of emotional changes after stroke. We aimed to investigate whether a multifactorial risk factor intervention program in patients with first-ever stroke or transient ischemic attack (TIA) can influence post-stroke anxiety and depressive symptoms in patients one year post-stroke. METHOD: The study population consisted of first-ever stroke and TIA patients allocated in a randomized, evaluator-blinded, controlled trial to care as usual or a structured and multidisciplinary follow-up including intensive treatment of vascular risk. The primary endpoint (cognition) has previously been reported. The secondary endpoint, reported here, was changes in the Hospital Anxiety and Depression Scale (HADS) from baseline to 12-month follow-up. RESULTS: One hundred and ninety-five patients were randomized. The estimated difference between treatment groups, in changes in HADS, from baseline to 12 months was -1.32 (95% confidence interval: -2.61, -0.04; P = 0.044) in favor of the intervention group. One year post-stroke, 4/85 (4.7%) patients in the intervention group and 12/89 (13.5%) in the control group suffered from depression (P = 0.045), while 7/85 (8.2%) patients in the intervention group and 13/89 (14.6%) patients in the control group suffered from anxiety (P = 0.19). CONCLUSION: A structured, multidisciplinary, multifactorial risk factor program including vascular risk factor management may be associated with reduced HADS scores and a lower prevalence of depressive symptoms one year after stroke.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Overtime reliability of medial temporal lobe atrophy rating in a clinical setting.

BACKGROUND: Medial temporal lobe atrophy (MTA) is one of the first magnetic resonance imaging (MRI) signs in patients with Alzheimer's disease (AD) and used as a measure of disease progression. Visual assessment of MTA is easy to perform but the reliability of MTA rating over time has not been studied. PURPOSE: To investigate what happens to the MTA rating scores if two radiologists rate the same MRI scans six times over a period of 1 year. MATERIAL AND METHODS: One hundred outpatients were included in this study. All patients underwent MRI with a protocol and sequences used for geriatric patients, according to local clinical standards. One neuroradiologist and one general radiologist independently of each other performed retrospective visual assessments of MTA six times, using the same scans, over a period of 1 year. RESULTS: Intra-rater kappa varied between κ 0.65 and 0.84 for the neuroradiologist and κ 0.38 and 0.74 for the general radiologist. Intra-rater weighted kappa (wκ) values showed almost perfect agreement for both investigators (wκ 0.83-0.94). Inter-rater reliability showed fair to moderate agreement, with the kappa value varying from κ 0.29 to 0.48 and weighted kappa values ranging from wκ 0.72 to 0.84. There was a statistically significant difference in rating between the two investigators. CONCLUSION: Visual assessment of MTA repeated over time has a high grade of reproducibility when performed by an experienced investigator. The reproducibility drops when assessment is rarely performed. Inter-rater reliability is low when two investigators not working together are compared.

Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population.

BACKGROUND: It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. PURPOSE: To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. MATERIAL AND METHODS: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and ≥87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. RESULTS: Significant correlation (r(s) = -0.32, P < 0.001, sin; and r(s) = -0.26, P < 0.001, dx) was found between hippocampal volume measurements and vaMTA. In normal ageing, almost 95% of ≤66-year-olds had a medial temporal lobe atrophy (MTA) score ≤1, with possible scores ranging from 0 to 4. Subjects aged 72, 78, and 81 years scored ≤2, while the two oldest age groups had scores ≤3. CONCLUSION: There was a highly significant correlation between volumetric measurements of the hippocampus and MTA scoring. In normal ageing, there is increasing MTA score. For non-demented elderly individuals ≤70 years, an MTA score of 0-1 may be considered normal, compared with MTA ≤2 for 70-80-years and MTA 3 for >80-year-old individuals.

Cohort profile: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) - a national research and quality registry with a biomaterial collection.

PURPOSE: The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data. PARTICIPANTS: The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009-2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders. FINDINGS TO DATE: All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources. FUTURE PLANS: The finish date of NorCog was originally in 2029. In 2021, the registry's legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.

Validity of the quantitative EEG statistical pattern recognition method in diagnosing Alzheimer's disease.

AIMS: To evaluate the use of quantitative EEG (qEEG) statistical pattern recognition in diagnosing Alzheimer's disease (AD). METHODS: qEEG was performed on 104 patients referred to a memory clinic. The qEEG results were compared to the clinical diagnosis made without access to the EEG results. RESULTS: Of 30 patients with a clinical diagnosis of AD, 22 were test positive. Of the 74 patients without AD, 34 were test negative. The qEEG result was found to correlate with atrophy of the medial temporal lobe demonstrated on cerebral MRI (p = 0.002) and with scores on neuropsychological tests. CONCLUSION: The qEEG was poor at diagnosing AD, as it produced many false-positive results.

Incidence and subtypes of MCI and dementia 1 year after first-ever stroke in patients without pre-existing cognitive impairment.

BACKGROUND: Post-stroke dementia is defined as any dementia occurring after stroke, and includes vascular, degenerative and mixed dementia. The aim of this study was to assess the incidence of dementia and mild cognitive impairment (MCI) one year after stroke in a population free from pre-stroke cognitive decline, and to investigate the different aetiological subtypes of post-stroke dementia and MCI, using a novel method of subclassification in order to separate vascular causes of MCI or dementia from a neurodegenerative disease. METHODS: All patients with a first-ever stroke and TIA admitted to the stroke unit of Asker and Bærum Hospital were invited. After 12 months, dementia and MCI were diagnosed. Sub-classification was made using MRI findings, the results of biomarkers in cerebrospinal fluid and the patients' clinical cognitive profile. RESULTS: 36 (19.6%) patients developed dementia during the first year after stroke and 69 (37.5%) developed MCI. Fourteen (13.3%) were diagnosed as suffering from degenerative cognitive disease, 34 (32.4%) from vascular cognitive disease, and 57 (54.3%) from mixed disease. CONCLUSION: Fifty-seven percent suffered from cognitive impairment one year after stroke and only one third from isolated vascular cognitive disease. Post-stroke cognitive impairment is complex with a high coexistence of vascular and degenerative changes.

[Clinical neurological examination of the geriatric patient]. / Klinisk nevrologisk undersøkelse av den geriatriske pasient.

BACKGROUND: Numerous physiological changes occur in the nervous system with increasing age. On clinical neurological examination, such changes may be misinterpreted as pathology in the nervous system. The objective of this article is to provide a review of the clinical neurological findings that may be caused by normal ageing. MATERIAL AND METHODS: The present manuscript is based on a non-systematic search in PubMed as well as on the clinical experience of the authors. RESULTS: Cognitive functions are usually fairly well preserved in old age, apart from executive functioning, psychomotor speed and episodic memory, which are reduced with increasing age. Physiological changes related to increasing age include, in particular, vertical eye movements (upwards), vibration sense, Achilles reflexes, primitive reflexes and motor speed. Muscle power is reduced by 20-40% in healthy individuals aged over 70 years. INTERPRETATION: A correct diagnosis based on findings in the neurological examination cannot be made without knowledge of how ageing affects the physiology of the nervous system. However, the evidence regarding physiological changes in the nervous system is limited, and more research is needed in this field.

Gait and balance one year after stroke; relationships with lesion side, subtypes of cognitive impairment and neuroimaging findings-a longitudinal, cohort study.

OBJECTIVES: The aims of this study are to investigate impairments of balance and gait in various types of dementia and cognitive impairment, and neuroimaging correlates in patients one year after first-ever stroke or transient ischemic attack. DESIGN: This is a longitudinal cohort study. PARTICIPANTS: 180 participants were included and a total of 156 participated in the assessments at the one-year follow-up. MAIN OUTCOME MEASURES: Measurements of balance and gait comprised the Berg Balance Scale (BBS) and the 10meter walk test (10MWT). Dementia was diagnosed with the International Classification of Diseases 10th revision. Magnet Resonance Imaging assessed vascular and degenerative changes in the brain. Multivariate linear regressions were conducted regarding associations between the motoric test performances, white matter lesions, lesion of the stroke and cognition. RESULTS: Cognitive impairment was significant associated with BBS (ß=-7.28, P=0.005) and MWS (ß=1.89, P=0.046) in the linear regression analyses. An association between 10MWT to living arrangements (ß=1.58, P=0.049) and lesion side of the stroke (ß=-1.50, P=0.037) was also observed. Pairwise associations with Mann-Whitney U test showed that participants with mixed pathology differed significantly from degenerative pathology (P=0.04, z=-2.1) with more impaired balance measured by BBS. CONCLUSIONS: Impaired balance and gait are associated with cognitive impairment, and a lesion in the right hemisphere is related to impaired gait in this cohort of stroke survivors.

Long-term effects on survival after a 1-year multifactorial vascular risk factor intervention after stroke or TIA: secondary analysis of a randomized controlled trial, a 7-year follow-up study.

BACKGROUND: Stroke and coronary heart disease share the same risk factors, and a multifactorial intervention after stroke may potentially result in the same reduction in cardiovascular mortality as seen after coronary events. We aimed to evaluate the effect on survival 7 years after a 1-year multifactorial risk factor intervention, and identify clinical predictors for long-term survival in a hospital-based cohort of patients with first-ever stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: We performed a secondary analysis of a randomized controlled trial including patients between February 2007 and July 2008 comparing an intensive risk factor intervention vs usual care the first year poststroke to prevent cognitive impairment. From February 2014 to July 2016, all patients were invited to a follow-up. For patients dying throughout the follow-up period, date of death was obtained from the medical record. Examination at baseline and 1-year follow-up included extensive assessment of vascular risk factors and cognitive assessments. RESULTS: A total of 195 patients were randomized. Mean (SD) age was 71.6 (12.5) years, 53.3% were male, mean (SD) body mass index (BMI) was 25.6 (4.1) kg/m2. During follow-up, 35 patients in the intervention group and 41 in the control group died. Kaplan-Meier survival estimates show no significant difference in intention-to-treat (ITT) population or complete case (CC) population (log-rank P=0.29 vs log-rank P=0.07). In multivariable Cox proportional hazards regression analyses, lower age and higher BMI was independently associated with long-term survival, adjusted HR (95% CI) 1.08 (1.05-1.11) per year and 0.91 (0.85-0.97) per kg/m2. CONCLUSION: In this post hoc analysis, we found no significant effect on survival after 7 years of a multifactorial risk factor program given during the first year after first-ever stroke or TIA. Higher BMI was an independent predictor for long-term survival in this cohort.

Impact of white matter lesions on cognition in stroke patients free from pre-stroke cognitive impairment: a one-year follow-up study.

BACKGROUND/AIM: Post-stroke cognitive impairment and dementia may be caused by pure vascular, pure degenerative or mixed disease. The relation between post-stroke cognitive impairment and the combination of vascular pathology and degenerative changes is less evaluated. We aimed to evaluate the associations between white matter lesions (WMLs) and patient performance 1 year after stroke on tests of executive functioning, memory and visuospatial function, adjusted for the effects of lifestyle and disease-related factors, including medial temporal lobe atrophy (MTLA). METHODS: Patients with a first-ever stroke or transient ischemic attack were invited to participate in the study. The associations between the cognitive test performances and WMLs were studied using linear regression [Trail Making Test B (TMT B) and 10-word test] and logistic regression (Clock Drawing Test). RESULTS: In total, 199 patients completed the follow-up. The TMT B (p = 0.029) and the 10-word test (p = 0.014) were significantly associated with WMLs; however, the Clock Drawing Test (p = 0.19) was not. The TMT B (p = 0.018) and the 10-word test (p ≤ 0.001) were both significantly associated with MTLA. CONCLUSION: Impaired executive functioning and memory are significantly associated with WMLs and MTLA. The mechanisms explaining post-stroke cognitive impairment are multifactorial, including different types of vascular pathology and coexisting vascular and degenerative changes.

Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer's disease.

OBJECTIVES: Cholesterol has been linked to Alzheimer's disease (AD) and plasma 24S-hydroxycholesterol (24OHC) has been suggested as a surrogate marker for brain cholesterol metabolism. This study investigates the relation of 24OHC as well as markers of extracerebral cholesterol homeostasis (lanosterol, lathosterol, cholesterol, LDL-C, HDL-C and 27-hydroxycholesterol) with brain volumes in memory clinic patients. METHODS: 96 patients (33 with subjective cognitive impairment--SCI; 36 with mild cognitive impairment--MCI; 27 with AD) referred to the Memory Clinic at Karolinska University Hospital, Sweden. Plasma assessments were done by isotope dilution-mass spectrometry. MRI measurements were done using custom-made software BMAP (imaging laboratory, Karolinska Institutet), running on HERMES platform. RESULTS: Ratios of 24-hydroxycholesterol, 27-hydroxycholesterol, lanosterol and lathosterol to cholesterol (R_24OHC, R_27OHC, R_lanosterol and R_lathosterol) were significantly lower in patients with AD. In the whole population, after controlling for age, sex, APOE genotype and statins, R_24OHC was positively related to gray matter (GM) fraction. However, when groups were considered separately, the relation to GM volume, GM and parenchymal fractions was significant in the SCI group only (p<0.05). There was a significant positive association between cholesterol and white matter (WM) volume, WM and parenchymal fractions in patients with AD. CONCLUSIONS: Plasma R_24OHC was lower in patients with AD, but R_24OHC was significantly related to brain volumes in the control group only. One reason may be the previously demonstrated abnormal expression of cholesterol 24S-hydroxylase in astrocytes in AD, which may limit the usefulness of this plasma marker in this specific disease. The findings on cholesterol agree with previous reports of decreasing plasma cholesterol levels in AD patients, suggesting a CNS-mediated effect on extracerebral cholesterol homeostasis.

[Genetic aspects of Alzheimer disease]. / Arvelige forhold ved Alzheimers sykdom.

BACKGROUND: To supply relevant information about the genetics of Alzheimer's disease. MATERIALS AND METHODS: Data from the literature (Medline) and personal experiences. RESULTS: Two well-known risks for developing Alzheimer's disease are established: advanced age and genetic factors. Mutations linked to autosomal dominant familial Alzheimer's disease are known in chromosomes 21, 14 and 1. A non-mendelian Alzheimer's disease with complex aetiology is linked to the apolipoprotein E in chromosome 19. INTERPRETATION: Children of patients with Alzheimer's disease have a three to four fold increased risk of developing the disease compared to a person without a parent with Alzheimer's disease. The diagnostic benefit of apolipoprotein E genotyping is still uncertain.