The five-items memory screen-extended variant: A tool for assessing memory.

BACKGROUND AND PURPOSE: The detection of memory impairment is an important part of dementia screening. However, the scope of memory measures in current screening batteries is limited. There is a need for a short yet sensitive instrument for early detection of memory impairment that could serve as a complement to existing globally oriented screening tests, for example, Mini-Mental State Examination (MMSE). To that end, the current study investigates the sensitivity and psychometric properties of the memory screening instrument The Five-Items Memory Screen -Extended Variant (FIMS-XV). METHODS: Hundred and forty-five participants included in the Gothenburg Mild Cognitive Impairment Study-27 patients with subjective cognitive impairment (SCI), 73 with mild cognitive impairment (MCI), and 45 with mild dementia-underwent cognitive screening including the MMSE and FIMS-XV. Ninety participants also underwent extensive neuropsychological testing. RESULTS: The FIMS-XV showed high internal consistency and strong correlations with established neuropsychological memory tests. Both the FIMS-XVdelayed recall score and the FIMS-XV total score differentiated mild dementia patients from patients with SCI and MCI. CONCLUSIONS: The FIMS-XV shows promise as a sensitive tool for screening for memory impairment in all putative phases of dementia.

Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels.

BACKGROUND/AIMS: The prognostic accuracy of mild cognitive impairment (MCI) in clinical settings is debated, variable across criteria, cut-offs, subtypes, and follow-up time. We aimed to estimate the prognostic accuracy of MCI and the MCI subtypes for dementia using three different cut-off levels. METHODS: Memory clinic patients were followed for 2 (n = 317, age 63.7 ± 7.8) and 4-6 (n = 168, age 62.6 ± 7.4) years. We used 2.0, 1.5, and 1.0 standard deviations (SD) below the mean of normal controls (n = 120, age 64.1 ± 6.6) to categorize MCI and the MCI subtypes. Prognostic accuracy for dementia syndrome at follow-up was estimated. RESULTS: Amnestic multi-domain MCI (aMCI-md) significantly predicted dementia under all conditions, most markedly when speed/attention, language, or executive function was impaired alongside memory. For aMCI-md, sensitivity increased and specificity decreased when the cut-off was lowered from 2.0 to 1.5 and 1.0 SD. Non-subtyped MCI had a high sensitivity and a low specificity. CONCLUSION: Our results suggest that aMCI-md is the only viable subtype for predicting dementia for both follow-up times. Lowering the cut-off decreases the positive predictive value and increases the negative predictive value of aMCI-md. The results are important for understanding the clinical prognostic utility of MCI, and MCI as a non-progressive disorder.

High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment.

BACKGROUND/AIMS: Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimer's disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment). METHODS: Memory clinic patients (SCI: n = 90; age: 59.8 ± 7.6 years; MCI: n = 160; age: 63.7 ± 7.0 years) included in the Gothenburg MCI study were examined at baseline. Variables were analyzed using logistic regression with SCI as dependent variable. RESULTS: Stress was more prevalent in SCI (51.1%) than MCI (23.1%); p < 0.0005. SCI patients had more previous depressive symptoms (p = 0.006), but showed no difference compared to MCI patients considering current depressive symptoms. A positive CSF AD profile was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001). Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a negative CSF AD profile (p = 0.036) predicted allocation to the SCI group. CONCLUSION: Psychosocial stress is more prevalent in SCI than previously acknowledged. The high prevalence and long-term occurrence of stress/depressive symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers strengthens the notion that AD is not the most likely etiology of SCI.

Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls.

INTRODUCTION: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737. METHODS: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate. Models were performed in a clinical sample of Swedish patients with BD (N = 114) and sex- and age-matched population controls (N = 104). RESULTS: No significant associations (regardless of correction for multiple testing) between the BDNF and CACNA1C risk variants and cognitive functioning were found in either patients or controls. CONCLUSIONS: Our results do not support that the common genetic risk variants in rs6265 and rs1006737 are associated with cognitive dysfunction.

Polymorphisms of dopamine pathway genes NRG1 and LMX1A are associated with cognitive performance in bipolar disorder.

OBJECTIVES: LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder. METHODS: In total, four SNPs were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient (IQ) score were run using risk variants of LMX1A (rs11809911, rs4657412, rs6668493) and NRG1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104). RESULTS: The risk variants of the rs11809911 SNP in LMX1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG1 were positively associated with IQ score (adjusted R(2) = 0.17, Q = 0.006) and memory/learning (adjusted R(2) = 0.24, Q = 0.001). The risk variants of the rs35753505 SNP in NRG1 were positively associated with language (adjusted R(2) = 0.11, Q = 0.006), visuospatial functions (adjusted R(2) = 0.23, Q = 0.001), and attention/speed (adjusted R(2) = 0.25, Q = 0.001). Results could not be replicated in controls. CONCLUSIONS: The risk variants of the rs35753505 SNP were associated with increased performance in several cognitive domains and IQ, whereas the risk variants of the rs11809911 SNP in LMX1A was associated with reduced IQ and memory/learning.

Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q)--a research tool discriminating between subjectively cognitively impaired patients and healthy controls.

BACKGROUND: Subjective cognitive impairment (SCI) is a potential early marker for actual cognitive decline. The cognitive manifestation of the SCI stage is, however, largely unknown. Self-report instruments developed especially for use in the SCI population are lacking, and many SCI studies have not excluded mild cognitive impairment and dementia. We developed and tested a patient-based questionnaire on everyday cognitive function aiming to discriminate between patients with subjective, but not objective, cognitive impairment and healthy controls. METHODS: Individuals experiencing cognitive impairment were interviewed to generate a pool of items. After condensing to 97 items, we tested the questionnaire in 93 SCI patients seeking care at a memory clinic (age M = 64.5 years, Mini-Mental State Examination (MMSE) M = 29.0) and 50 healthy controls (age M = 69.6 years, MMSE M = 29.3). Further item reduction was conducted to maximize that remaining items would discriminate between SCI patients and controls, using a conservative α level and requiring medium to high effect sizes. Internal consistency reliability and convergent validity was subsequently examined. RESULTS: Forty-five items discriminated between the groups, resulting in the Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q). Internal consistency was high and correlations to a single question on memory functioning were of medium to large sizes. Most remaining items were related to the memory domain. CONCLUSION: The SASCI-Q discriminates between SCI patients and healthy controls and demonstrates satisfying psychometric properties. The instrument provides a research method for examining SCI and forms a foundation for future examining which SCI symptoms predict objective cognitive decline. The cognitive manifestation of the SCI stage is mostly related to experiences of memory deficits.

Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-ß Protein Precursor ß in the Subcortical Small Vessel Type of Dementia.

BACKGROUND: The subcortical small vessel type of dementia (SSVD) is a common subtype of vascular dementia, but there is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers. OBJECTIVE: We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid-ß protein precursor α (sAßPPα), sAßPPß, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD), and mixed dementia (combined AD and SSVD). METHODS: This was a mono-center study of patients with SSVD (n = 38), AD (n = 121), mixed dementia (n = 62), and controls (n = 96). The CSF biomarkers were measured using immunoassays, and their independent contribution to the separation between groups were evaluated using the Wald test. Then, the area under the receiver operating characteristics curve (AUROC) and 95% confidence intervals (CIs) were calculated. RESULTS: Elevated neurofilament light chain (NFL) and decreased sAßPPß independently separated SSVD from controls, and sAßPPß also distinguished SSVD from AD and mixed dementia. The combination of NFL and sAßPPß discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sAßPPß combined with the core AD biomarkers (amyloid-ß42, total tau, and phosphorylated tau181) had a high ability to separate SSVD from AD (AUROC 0.886, 95% CI: 0.830-0.942) and mixed dementia (AUROC 0.903, 95% CI: 0.838-0.968). CONCLUSIONS: The high accuracy of NFL and sAßPPß to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sAßPPß in combination with the core AD biomarkers.

Monte Carlo feature selection and rule-based models to predict Alzheimer's disease in mild cognitive impairment.

The objective of the present study was to evaluate a Monte Carlo feature selection (MCFS) and rough set Rosetta pipeline for generating rule-based models as a tool for comprehensive risk estimates for future Alzheimer's disease (AD) in individual patients with mild cognitive impairment (MCI). Risk estimates were generated on the basis of age, gender, Mini-Mental State Examination scores, apolipoprotein E (APOE) genotype and the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phospho-tau(181) (P-tau) and the 42 amino acid form of amyloid ß (Aß42) in two sets of longitudinally followed MCI patients (n = 217 in total). The predictive model was created in Rosetta, evaluated with the standard tenfold cross-validation approach and tested on an external set. Features were ranked and selected by the MCFS algorithm. Using the combined pipeline of MCFS and Rosetta, it was possible to predict AD among patients with MCI with an area under the receiver operating characteristics curve of 0.92. Risk estimates were produced for the individual patients and showed good correlation with actual diagnosis in cross validation, and on an external dataset from a new study. Analysis of the importance of attributes showed that the biochemical CSF markers contributed the most to the predictions, and that added value was gained by combining several biochemical markers. Despite a correlation with the biochemical markers, the genetic marker APOE ε4 did not contribute to the predictive power of the model.

Low cerebrospinal fluid sulfatide predicts progression of white matter lesions: The LADIS study.

BACKGROUND/AIMS: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. METHODS: CSF from elderly individuals with WML was analyzed for amyloid markers, total τ, hyperphosphorylated τ, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). RESULTS: 37 subjects (age 73.6 ± 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). CONCLUSION: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.

Response burden and questionnaire length: is shorter better? A review and meta-analysis.

BACKGROUND: Response burden is often defined as the effort required by the patient to answer a questionnaire. A factor that has been proposed to affect the response burden is questionnaire length, and this burden is manifested in, for example, response rate. Even though response burden is frequently mentioned as a reason for abridging questionnaires, evidence to support the notion that shorter instruments are preferable is limited. OBJECTIVES: This study aimed to accumulate, analyze, and discuss evidence regarding the association between response burden, as measured by response rate, and questionnaire length. METHODS: A systematic literature review and meta-analysis of studies reporting response rates in relation to questionnaire length was performed. A Cochran-Mantel-Haenszel test stratified by study using the Breslow-Day test was undertaken to investigate homogeneity of the odds ratios. RESULTS: Thirty-two reports were identified, of which 20 were eligible for inclusion in the meta-analysis. Three studies used patient input as main outcome when evaluating response burden. In the meta-analysis, a general association between response rate and questionnaire length was found (P ≤ 0.0001). Response rates were lower for longer questionnaires, but because the P value for test of homogeneity was P = 0.03, this association should be interpreted with caution because it is impossible to separate the impact of content from length of the questionnaires. CONCLUSION: Given the inherently problematic nature of comparing questionnaires of various lengths, it is preferable to base decisions on use of instruments on the content rather than the length per se.

Regional lithium prescription rates and recurrence in bipolar disorder.

BACKGROUND: Lithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes. AIMS: To estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden. METHOD: Data from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately. RESULTS: Lithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately. CONCLUSIONS: The advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.

Two-year outcome of MCI subtypes and aetiologies in the Göteborg MCI study.

OBJECTIVE: The objective was to study the 2-year outcome of subjects diagnosed as having mild cognitive impairment (MCI). METHODS: Two hundred and nine subjects diagnosed as having MCI were examined with a comprehensive neuropsychological test battery and followed up after 2 years. RESULTS: After 2 years, 34 subjects (16%) were lost for follow-up. Those subjects did not differ significantly in terms of MCI subclassification, MMSE score or age and education. Of the 175 subjects followed up, eight (4.5%) had improved to normal, two with amnestic MCI, one from multiple domains MCI, three with single domain MCI and two without any significant impairment at baseline. Forty-four subjects (25%) had progressed to dementia. Of these, 35 were from the multidomain amnestic group and nine from the multidomain non-amnestic group. The combination of Alzheimer-typical biomarkers (total-tau and amyloid beta) and multidomain amnestic MCI was the strongest predictor of progression to Alzheimer's disease, while vascular disease and multidomain amnestic MCI preceded mixed and vascular dementia. CONCLUSION: The results suggest that memory impairment alone, or impairment in any one cognitive domain alone, is a rather benign condition. Impairment in several cognitive domains is associated with a more severe outcome over 2 years. Also, 20% of the subjects who progressed to dementia, including Alzheimer's disease, did not show memory impairment at baseline, which suggests that memory impairment is not always the first symptom of even the most common dementia disorders.

Cognitive profiles of incipient dementia in the Goteborg MCI study.

OBJECTIVE: To study which cognitive profiles of incipient dementia strongest predict the conversion to Alzheimer's disease (AD) and mixed dementia (MD)/vascular dementia (VaD). METHODS: 260 subjects with mild cognitive impairment (MCI) were included in the study and 209 (79%) were followed up after 2 years. At baseline, the subjects were assessed with a neuropsychological battery covering the cognitive domains speed/attention, memory, visuospatial, language and executive functions. RESULTS: After 2 years, 9 subjects were considered normal, 148 had stationary MCI and 47 (23%) had converted to dementia. Twenty subjects were diagnosed with AD, 15 with MD and 9 with VaD. The others were 2 with unspecified dementias and 1 with primary progressive aphasia. Dementia converters had a high proportion of impairment in all cognitive domains. The profiles of incipient AD and MD/VaD differed, with memory, visuospatial and language symptoms preceding AD, and executive and speed/attention symptoms preceding MD/VaD. CONCLUSIONS: The risk of converting to dementia is increased when domains in addition to memory are impaired. The incipient AD and MD/VaD profiles differed quite clearly. Considering that the vascular group consisted of a majority of patients with MD, the differences are convincing - vascular disease seems to have an essential impact on cognition.

Characteristic Biomarker and Cognitive Profile in Incipient Mixed Dementia.

BACKGROUND: Research has shown that mixed dementia is more common than previously believed but little is known of its early stages. OBJECTIVE: To examine if incipient mixed dementia can be differentiated from incipient Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SVD) using neuropsychological tests, cerebrospinal fluid (CSF) markers, and magnetic resonance imaging markers. METHODS: We included 493 patients and controls from the Gothenburg MCI study and used the dementia groups for marker selection (CSF total-tau (T-tau), phospho-tau (P-tau), and amyloid-ß42 (Aß42), 11 neuropsychological tests, and 92 regional brain volumes) and to obtain cut-off values which were then applied to the MCI groups. RESULTS: Incipient mixed dementia was best differentiated from incipient AD by the Word fluency F-A-S test and the Trail making test A. CSF T-tau, P-tau, and Aß42 differentiated incipient mixed dementia from incipient SVD. CONCLUSION: Incipient mixed dementia is characterized by an AD-like biomarker profile and an SVD-like cognitive profile. Incipient mixed dementia can be separated from incipient AD and incipient SVD using CSF markers and cognitive testing.

Latent Cognitive Profiles Differ Between Incipient Alzheimer's Disease and Dementia with Subcortical Vascular Lesions in a Memory Clinic Population.

BACKGROUND: It is unclear if latent cognitive profiles can distinguish between dementia with subcortical vascular lesions and Alzheimer's disease (AD) at the incipient stage, and if they differ in performance from the Petersen subtypes. OBJECTIVE: To identify latent cognitive profiles in a naturalistic population of patients from a memory clinic sample, and investigate the derived classes not only in terms of conversion to AD, but also in terms of conversion to dementia with subcortical vascular lesions. Another objective was to compare the derived classes to the Petersen subtypes. METHODS: We performed a latent profile analysis (LPA) on standardized neuropsychological test scores from 476 memory clinic patients (age 64±8) without dementia, and analyzed progression to dementia after 2 years. RESULTS: The LPA resulted in two classes with impaired cognition (Amnestic and Slow/Dysexecutive) and two classes with normal cognition (Normal-Low and Normal-High cognition). Belonging to the Amnestic class predicted progression to all-cause dementia and to AD; belonging to the Slow/Dysexecutive class predicted progression to all-cause dementia, AD, and dementia with subcortical vascular lesions. Of the Petersen MCI subtypes, only amnestic multi-domain MCI predicted progression to all-cause dementia, AD, and dementia with subcortical vascular lesions. CONCLUSION: Latent cognitive profiles separated between AD and dementia with subcortical vascular lesions, while the Petersen subtypes did not. However, similar to the Petersen subtypes, LPA classes work better for ruling out progression to dementia than for case finding.

Subcortical vascular dementia biomarker pattern in mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is an etiologically unclear disorder. Cerebrospinal fluid (CSF) biomarkers are potentially useful for the differentiation between various MCI etiologies. AIM: The aim of the study was to assess whether baseline CSF hyperphosphorylated tau (P-tau), total tau (T-tau), amyloid beta 1-42 (Abeta(42)) and neurofilament light (NF-L) in patients with MCI could predict subcortical vascular dementia (SVD) and Alzheimer's disease (AD) at follow-up. METHODS: Biomarker levels were assessed by Luminex xMAP technology and ELISA. RESULTS: Increased baseline concentrations of NF-L significantly separated MCI-SVD from stable MCI. The MCI-SVD patients were inseparable from stable MCI but separable from patients developing AD (MCI-AD) on the basis of Abeta(42,) T-tau and P-tau(181) levels. CONCLUSION: A combination of the biomarkers Abeta(42), T-tau, P-tau(181) and NF-L has the potential to improve the clinical separation of MCI-SVD patients from stable MCI and MCI-AD patients.

Episodic memory and speed/attention deficits are associated with Alzheimer-typical CSF abnormalities in MCI.

UNLABELLED: Mild cognitive impairment (MCI) is regarded as the prodromal stage of dementia disorders, such as Alzheimer's disease (AD). OBJECTIVE: To compare the neuropsychological profiles of MCI subjects with normal concentrations of total tau (T-tau) and Abeta42 in CSF (MCI-norm) to MCI subjects with deviating concentrations of the biomarkers (MCI-dev). MCI-norm (N = 73) and MCI-dev (N = 73) subjects were compared to normal controls (N = 50) on tests of speed/attention, memory, visuospatial function, language and executive function. RESULTS: MCI-norm performed overall better than MCI-dev, specifically on tests of speed and attention and episodic memory. When MCI-dev subjects were subclassified into those with only high T-tau (MCI-tau), only low Abeta42 (MCI-Abeta) and both high T-tau and low Abeta42 (MCI-tauAbeta), MCI-tauAbeta tended to perform slightly worse. MCI-tau and MCI-Abeta performed quite similarly. CONCLUSIONS: Considering the neuropsychological differences, many MCI-norm probably had more benign forms of MCI, or early non-AD forms of neurodegenerative disorders. Although most MCI-dev performed clearly worse than MCI-norm on the neuropsychological battery, some did not show any deficits when compared to age norms. A combination of CSF analyses and neuropsychology could be a step toward a more exact diagnosis of MCI as prodromal AD.

Similar pattern of atrophy in early- and late-onset Alzheimer's disease.

INTRODUCTION: Previous research on structural changes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have reported inconsistent findings. METHODS: In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer. Study participants (N = 145) included 63 patients with AD, (24 patients with EOAD [aged ≤65 years], 39 patients with LOAD [aged >65 years]), 25 healthy controls aged ≤65 years, and 57 healthy controls aged >65 years. RESULTS: Hippocampal atrophy is the most prominent feature of both EOAD and LOAD compared with controls. Direct comparison between EOAD and LOAD showed that the differences between the groups did not remain after correcting for age. DISCUSSION: Structurally, EOAD and LOAD does not seem to be different nosological entities. The difference in brain volumes between the groups compared with controls is likely due to age-related atrophy.

Better prognostic accuracy in younger mild cognitive impairment patients with more years of education.

INTRODUCTION: Age and years of education influence the risk of dementia and may impact the prognostic accuracy of mild cognitive impairment subtypes. METHODS: Memory clinic patients without dementia (N = 358, age 64.0 ± 7.9) were stratified into four groups based on years of age (≤64 and ≥65) and education (≤12 and ≥13), examined with a neuropsychological test battery at baseline and followed up after 2 years. RESULTS: The prognostic accuracy of amnestic multi-domain mild cognitive impairment for dementia was highest in younger patients with more years of education and lowest in older patients with fewer years of education. Conversely, conversion rates to dementia were lowest in younger patients with more years of education and highest in older patients with fewer years of education. DISCUSSION: Mild cognitive impairment subtypes and demographic information should be combined to increase the accuracy of prognoses for dementia.

Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years.

This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau(181) (P-tau(181)) and amyloid-beta(1-42) (Abeta(1-42)). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau(181) levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p<0.01), while baseline Abeta(1-42) levels were lower (p<0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.