Neurological soft signs and brain morphology in people living with HIV.

Neurological soft signs (NSS) are a common feature of severe psychiatric disorders such as schizophrenia but are also prevalent in organic brain diseases like HIV-associated neurocognitive disorder (HAND) or Alzheimer's disease. While distinct associations between NSS, neurocognition, and cerebral regions were demonstrated in schizophrenia, these associations still have to be elucidated in HIV. Therefore, we investigated 36 persons with HIV of whom 16 were neurocognitively healthy and 20 were diagnosed with HAND. NSS were assessed using the Heidelberg scale. NSS scores were correlated with gray matter (GM) using whole brain voxel-based morphometry. Results showed significantly elevated NSS in the HAND group when compared to the neurocognitively healthy with respect to NSS total score and the subscores "orientation" and "complex motor tasks". While the two groups showed only minor, non-significant GM differences, higher NSS scores (subscales "motor coordination", "orientation") were significantly correlated with GM reduction in the right insula and cerebellum (FWE-corrected). Our results corroborate elevated NSS in HIV+ patients with HAND in contrast to cognitively unimpaired patients. In addition, cerebral correlates of NSS with GM reductions in insula and cerebellum were revealed. Taken together, NSS in this patient group could be considered a marker of cerebral damage and neurocognitive deficits.

Neurological soft signs and cognition in the late course of chronic schizophrenia: a longitudinal study.

Neurological soft signs (NSS) are minor ('soft') neurological abnormalities in sensory and motor performances, which are frequently reported in patients with schizophrenia at any stage of their illness. It has been demonstrated that NSS vary in the clinical course of the disorder: longitudinally NSS decrease in parallel with remission of psychopathological symptoms, an effect which mainly applies to patients with a remitting course. These findings are primarily based on patients with a first episode of the disorder, while the course of NSS in patients with chronic schizophrenia and persisting symptoms is rather unknown. Therefore, we investigated NSS twice in 21 patients with chronic schizophrenia (initial mean duration of illness: 23 ± 11 years) with a mean follow-up interval of 7 years. NSS were evaluated by the Heidelberg Scale, established instruments were used to rate neuropsychological performance and psychopathological symptoms. NSS showed significant increases on the subscales "motor coordination" and "integrative functions", while positive and negative symptoms, including apathy, showed only minor, non-significant changes. Verbal memory, verbal fluency, and cognitive flexibility along with severity of global cognitive deficits demonstrated a significant deterioration. Regression analyses identified executive dysfunction (cognitive flexibility and verbal fluency) at baseline as significant predictors of NSS increase at follow-up. Our findings indicate that NSS deteriorate in the long-term course of chronic schizophrenia. This effect may be accounted for by a decrease of executive functions and logical memory, which can be attributed to premature brain aging.

[Dental treatment in old age-When and what is indicated?] / Zahnärztliche Therapie im Alter ­ Wann ist was indiziert?

In the past few years the oral health of seniors has improved and more seniors retain their natural teeth until old age; however, the prevalence of oral diseases among seniors is still very high and a serious problem. Good oral health is, however, relevant for seniors as it influences the chewing function, the nutritional status and general satisfaction. In addition, diseases of the oral cavity show interactions with general health. The current article therefore provides an evidence-based overview of the oral health of seniors and highlights important relationships (nutritional status, oral health-related quality of life, general health). It also gives advice on when dental treatment may be indicated. Furthermore, instruments for assessing oral health, chewing function and oral health-related quality of life are presented and explained.

Is compromised oral health associated with a greater risk of mortality among nursing home residents? A controlled clinical study.

AIM: The objective of this controlled clinical study was to evaluate the association between oral health and 1-year mortality among nursing home residents with or without oral health intervention. METHODS: This research was part of a multidisciplinary intervention study (EVI-P) performed in 14 nursing homes in Germany. Two-hundred and nineteen nursing home residents were included in the study and assigned to an intervention group, for which dental health education was offered and ultrasonic baths were used for denture cleaning (n = 144), or to a control group (n = 75). Before the intervention, each participant was examined, and dental status, plaque control record (PCR), Denture Hygiene Index, and results from the Revised Oral Assessment Guide were recorded. Amount of care needed and dementia were also assessed, by use of the Barthel Index and the Mini Mental State Examination, respectively. Participant mortality was determined after 12 months, and bivariate analysis and logistic regression models were used to evaluate possible factors affecting mortality. RESULTS: Bivariate analysis detected a direct association between greater mortality and being in the control group (p = .038). Participants with higher PCR were also more likely to die during the study period (p = .049). For dentate participants, the protective effect of being in the intervention group was confirmed by multivariate analysis in which covariates such as age and gender were considered. CONCLUSION: Oral hygiene and oral health seem to affect the risk of mortality of nursing home residents. Dental intervention programs seem to reduce the risk of 1-year mortality among nursing home residents having remaining natural teeth. Further studies, with larger sample sizes and evaluation of the causes of death, are necessary to investigate the reasons for these associations.

The European DTI Study on Dementia - A multicenter DTI and MRI study on Alzheimer's disease and Mild Cognitive Impairment.

The European DTI Study on Dementia (EDSD) is a multicenter framework created to study the diagnostic accuracy and inter-site variability of DTI-derived markers in patients with manifest and prodromal Alzheimer's disease (AD). The dynamically growing database presently includes 493 DTI, 512 T1-weighted MRI, and 300 FLAIR scans from patients with AD dementia, patients with Mild Cognitive Impairment (MCI) and matched Healthy Controls, acquired on 13 different scanner platforms. The imaging data is publicly available, along with the subjects' demographic and clinical characterization. Detailed neuropsychological information, cerebrospinal fluid information on biomarkers and clinical follow-up diagnoses are included for a subset of subjects. This paper describes the rationale and structure of the EDSD, summarizes the available data, and explains how to gain access to the database. The EDSD is a useful database for researchers seeking to investigate the contribution of DTI to dementia diagnostics.

Hippocampal formation alterations differently contribute to autobiographic memory deficits in mild cognitive impairment and Alzheimer's disease.

Autobiographical memory (AM) is part of declarative memory and includes both semantic and episodic aspects. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. Previous MRI studies in AD patients have showed that deficits in semantic and episodic AM are associated with hippocampal alterations. However, the question which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits of AM in individuals with mild cognitive impairment (MCI) and AD patients has not been investigated so far. Hundred and seven participants (38 AD patients, 38 MCI individuals and 31 healthy controls [HC]) underwent MRI at 3 Tesla. AM was assessed with a semi-structured interview (E-AGI). FreeSurfer 5.3 was used for hippocampal parcellation. Semantic and episodic AM scores were related to the volume of 5 hippocampal subfields and cortical thickness in the parahippocampal and entorhinal cortex. Both semantic and episodic AM deficits were associated with bilateral hippocampal alterations. These associations referred mainly to CA1, CA2-3, presubiculum, and subiculum atrophy. Episodic, but not semantic AM loss was associated with cortical thickness reduction of the bilateral parahippocampal and enthorinal cortex. In MCI individuals, episodic, but not semantic AM deficits were associated with alterations of the CA1, presubiculum and subiculum. Our findings support the crucial role of CA1, presubiculum, and subiculum in episodic memory. The present results implicate that in MCI individuals, semantic and episodic AM deficits are subserved by distinct neuronal systems.

Poor dental hygiene and periodontal health in nursing home residents with dementia: an observational study.

Poor oral health conditions are well documented in the institutionalized elderly, but the literature is lacking research on relationships between dementia and periodontal health in nursing home residents. The purpose of this cohort study, therefore, was to assess whether dementia is associated with poor oral health/denture hygiene and an increased risk of periodontal disease in the institutionalized elderly. A total of 219 participants were assessed using the Mini Mental State Examination (MMSE) to determine cognitive state. According to the MMSE outcome, participants scoring ≤20 were assigned to dementia group (D) and those scoring >20 to the non-dementia group (ND), respectively. For each of the groups D and ND, Gingival Bleeding Index (GBI) and Denture Hygiene Index (DHI) linear regression models were used with the confounders age, gender, dementia, number of comorbidities and number of permanent medications. To assess the risk factors for severe periodontitis as measured by the Community Index of Periodontal Treatment Needs, a logistic regression analysis was performed. Statistical analysis revealed no significant differences of GBI as well of DHI for demented and healthy subjects (p > 0.05). Severe periodontitis was detected in 66 % of participants with dementia. The logistic regression showed a 2.9 times increased risk among demented participants (p = 0.006). Oral hygiene, denture hygiene and periodontal health are poor in nursing home residents. The severity of oral problems, primarily periodontitis, seems to be enhanced in subjects suffering from dementia. Longitudinal observations are needed to clarify the cause-reaction relationship.

Changes of tooth color in middle and old age: A longitudinal study over a decade.

OBJECTIVE: To evaluate changes in tooth color for 2 age cohorts (younger cohort, YC: 1950-1952; older cohort, OC: 1930-1932) over a mean observation period of 8 years. MATERIAL AND METHODS: Sixty-one participants with 106 upper central incisors were subjected to baseline and follow-up examinations (YC: n = 46/OC: n = 15). International Commission on Illumination color coordinates of 1 or 2 unrestored test teeth for each participant were recorded by use of a spectrophotometer (VITA Easyshade 1) during both measurement times. Changes of color coordinates during the study period were evaluated by use of generalized linear mixed models with the variable "participant" as random effect. ΔEab and E2000 color differences were calculated between baseline and follow-up. RESULTS: Significant changes in color coordinates were observed, with the exception of lightness in OC. The direction of the changes depended on the cohort. A decrease of lightness (value) was observed in YC (ΔL = 4.0; P < .001) whereas in OC chroma increased (ΔC = -3.3; P < .001). For both groups, a significant shift to more reddish tooth colors was observed. In almost all cases, color differences between baseline and follow-up exceeded the 50:50 acceptability thresholds for color differences (ΔE = 2.7) in both YC (≈90%) and OC (≈80%). CONCLUSIONS: For both quinquagenarians and septuagenarians, clinically relevant changes in tooth color were observed after a decade; these could affect the long-term success of prosthetic restorations in terms of a satisfactory color match between natural teeth and dental prostheses. In contrast with the findings of cross-sectional studies, the changes were partially age-group-specific. CLINICAL SIGNIFICANCE: Tooth color can change over a decade. When fixed dental prostheses are planned, one should consider that changes of tooth color could lead to mismatch between a restoration and adjacent teeth during the period in clinical service.

The COMTp.Val158Met Polymorphism and Cognitive Performance in Adult Development, Healthy Aging and Mild Cognitive Impairment.

BACKGROUND: The impact of genetic polymorphisms on cognition is assumed to increase with age as losses of brain resources have to be compensated for. We investigate the relation of catechol-O-methyltransferase (COMT)p.Val158Met polymorphism and cognitive capacity in the course of adult development, healthy aging and the development of mild cognitive impairment (MCI) in two birth cohorts of subjects born between 1930 and 1932 or between 1950 and 1952. METHODS: Thorough neuropsychological assessment was conducted in a total of 587 participants across three examination waves between 1993 and 2008. The COMT genotype was determined as a restriction fragment length polymorphism after PCR amplification and digestion with NlaIII. RESULTS: Significant effects of the COMTp.Val158Met polymorphism were identified for attention and cognitive flexibility in the younger but not the older cohort. CONCLUSION: These results confirm the importance of the COMTp.Val158Met genotype on tasks assessing attention and cognitive flexibility in midlife but not in healthy aging and the development of MCI. Our findings suggest that the influence of COMT changes as a function of age, decreasing from midlife to aging.

Neurocognitive Deficits and Effects of Cognitive Reserve in Mild Cognitive Impairment.

BACKGROUND/AIMS: Mild cognitive impairment (MCI) is a frequent syndrome in the older population, which involves an increased risk to develop Alzheimer's disease (AD). The latter can be modified by the cognitive reserve, which can be operationalized by the length of school education. MCI can be differentiated into four subtypes according to the cognitive domains involved: amnestic MCI, multiple-domain amnestic MCI, non-amnestic MCI and multiple-domain non-amnestic MCI. While neurocognitive deficits are a constituent of the diagnosis of these subtypes, the question of how they refer to the cognitive reserve still needs to be clarified. METHODS: We examined neuropsychological deficits in healthy controls, patients with MCI and patients with mild AD (n = 485) derived from a memory clinic. To reduce the number of neuropsychological variables, a factor analysis with varimax rotation was calculated. In a second step, diagnostic groups including MCI subtypes were compared with respect to their clinical and neuropsychological characteristics including cognitive reserve. RESULTS: Most MCI patients showed the amnestic multiple-domain subtype followed by the pure amnestic subtype, while the non-amnestic subtypes were rare. The amnestic subtype displayed a significantly higher level of cognitive reserve and higher MMSE scores than the amnestic multiple-domain subtype, which was in most cases characterized by additional psychomotor and executive deficits. CONCLUSIONS: These findings confirm earlier reports revealing that the amnestic multiple-domain subtype is the most frequent one and indicating that a high cognitive reserve may primarily prevent psychomotor and executive deficits in MCI.

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism.

Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism.

CODEMamb - an observational communication behavior assessment tool for use in ambulatory dementia care.

INTRODUCTION: Communication improves well-being and quality of life for both people with dementia and their professional and family caregivers. Individualized communication, as required in informed consent procedures and psychosocial interventions, can improve quality of life, especially in ambulatory settings. However, few valid and reliable instruments exist that enable communication to be assessed and communication and behavioral resources to be identified. We, therefore, extended and adapted the newly developed observational instrument CODEM for use in ambulatory settings (CODEMamb). METHODS AND RESULTS: Reliability and validity of the new instrument were studied in a total of 171 patients, whereby principal component analysis revealed three important factors: relationship aspects, verbal communication behavior and nonverbal communication behavior. CODEMamb[Formula: see text]s internal consistency, interrater and retest reliability were satisfactory to excellent. Convergent validity indices, as shown by examining correlations with similar but not identical constructs (CERAD-NP verbal subscales), were medium-high, while the divergent validity index (constructional praxis) was relatively low. The relationship to peer-rating remained nonsignificant. Criterion validity was investigated in groups of patients in accordance with their cognitive status. As expected, verbal communication abilities deteriorate faster than the relationship aspects of communication as the disease progresses. CONCLUSIONS: In summary, CODEMamb is a reliable and valid instrument that can be used to collect important information with the ultimate aim of supporting communication with people with dementia.

Disk displacement, eccentric condylar position, osteoarthrosis - misnomers for variations of normality? Results and interpretations from an MRI study in two age cohorts.

BACKGROUND: Clinical decision-making and prognostic statements in individuals with manifest or suspected temporomandibular disorders (TMDs) may involve assessment of (a) the position of articular disc relative to the mandibular condyle, (b) the location of the condyle relative to the temporal joint surfaces, and (c) the depth of the glenoid fossa of the temporomandibular joints (TMJs). The aim of this study was twofold: (1) Determination of the prevalence of these variables in two representative population-based birth cohorts. (2) Reinterpretation of the clinical significance of the findings. METHODS: From existing magnetic resonance imaging (MRI) scans of the TMJs that had been taken in 2005 and 2006 from 72 subjects born between 1930 and 1932 and between 1950 and 1952, respectively, the condylar position at closed jaw was calculated as percentage displacement of the condyle from absolute centricity. By using the criteria introduced by Orsini et al. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:489-97, 1998), a textbook-like disc position at closed jaw was distinguished from an anterior location. TMJ morphology of the temporal joint surfaces was assessed at open jaw by measuring the depth of the glenoid fossa, using the method proposed by Muto et al. (J Oral Maxillofac Surg 52:1269-72, 1994). Frequency distributions were recorded for the condylar and disc positions at closed jaw. Student's t-test with independent samples was used as test of significance to detect differences of condylar positions between the age cohorts (1930 vs. 1950) and the sexes. The significance levels were set at 5%. First, the results from the measurement of the age cohorts were compared without differentiation of sexes, i.e., age cohort 1930-1932 versus age cohort 1950-1952. Subsequently, the age cohorts were compared by sex, i.e., men in cohort 1930-1932 versus men in cohort 1950-1952, and women in cohort 1930-1932 women men in cohort 1950-1952. RESULTS: In both cohorts, condylar position was characterized by great variability. About 50% of the condyles were located centrically, while the other half was either in an anterior or in a posterior position. In both female cohorts, a posterior position predominated, whereas a centric position prevailed among men. Around 75% of the discs were positioned textbook-like, while the remaining forth was located anteriorly. Age had no statistically significant influence on condylar or on disc position. Conversely, comparison between the age groups revealed a statistically significant decrease of the depth of the glenoid fossa in both older cohorts. This age-dependent changes may be interpreted as flattening of the temporal joint surfaces. CONCLUSIONS: We call for a re-interpretation of imaging findings because they may insinuate pathology which usually is not present. Instead, anterior or posterior positions of the mandibular condyle as well as an anterior location of the articular disc should be construed as a variation of normalcy. Likewise, flattening of articular surfaces of the TMJs may be considered as normal adaptive responses to increased loading, rather than pathological degenerative changes. TRIAL REGISTRATION: Not applicable.

Association of cortical thickness and neurological soft signs in patients with chronic schizophrenia and healthy controls.

BACKGROUND: Neurological soft signs (NSS), i.e. subtle neurological abnormalities, have been frequently found in schizophrenia. Neuroimaging studies in schizophrenia have shown abnormal cortical thickness changes across the cortical mantle. However, few studies have examined relationships between NSS and cortical thickness abnormalities in schizophrenia. METHOD: A sample of 18 patients with chronic schizophrenia and 20 age-matched healthy controls were included. Cortical thickness was assessed on high-resolution 3-tesla magnetic resonance imaging by using FreeSurfer software and NSS were rated on the Heidelberg Scale. RESULTS: Significant negative correlations between NSS and cortical thickness were found in the prefrontal, inferior temporal, superior parietal, postcentral, and supramarginal cortices in the schizophrenia patients. In the controls, however, this negative correlation was found in the anterior cingulate, pericalcarine and superior/middle temporal regions. CONCLUSION: Our results not only confirmed the association between NSS and cortical thickness in chronic schizophrenia but also indicated that patients and controls have different anatomical substrates of NSS.

Kinematic parameters of throwing performance in patients with schizophrenia using a markerless motion capture system.

Motor dysfunction is consistently reported but understudied in schizophrenia. It has been hypothesized that this abnormality may reflect a neuro-developmental disorder underlying this illness. The main goal of this study was to analyze movement patterns used by participants with schizophrenia and healthy controls during overarm throwing performance, using a markerless motion capture system. Thirteen schizophrenia patients and 16 healthy control patients performed the overarm throwing task in a markerless motion capture system. Participants were also examined for the presence of motor neurological soft signs (mNSS) using the Brief Motor Scale. Schizophrenia patients demonstrated a less developed movement pattern with low individualization of components compared to healthy controls. The schizophrenia group also displayed a higher incidence of mNSS. The presence of a less mature movement pattern can be an indicator of neuro-immaturity and a marker for atypical neurological development in schizophrenia. Our findings support the understanding of motor dysfunction as an intrinsic part of the disorder of schizophrenia.

Oral health and apraxia among institutionalized elderly people--a pilot study.

OBJECTIVE: Poor oral hygiene and dental health are very common among the institutionalized elderly. The purpose of this study was to evaluate the association of apraxia with oral hygiene and/or health. MATERIALS AND METHODS: Ninety-two residents of 13 long-term care homes in southwest Germany participated in the study. For each participant, ideomotor apraxia scoring (AS) was conducted and demographic variables were collected. Participants underwent a comprehensive dental examination to assess the oral health indices gingival bleeding index (GBI), community periodontal index of treatment needs (CPITN) and denture hygiene index (DHI). Statistical comparison of dental indices among apraxic and non-apraxic individuals (cut-off < 45) was performed by use of t-tests. In addition, linear regression models were constructed with the dental indices as dependent variables. Each model was fitted with the dichotomized variable AS (pathologic or healthy) and adjusted for age and sex. RESULTS: Mean (SD) GBI of 48.5 (25.9), CPITN of 2.9 (0.7) and DHI of 82.6 (14.6) were observed among the participants. Statistical analysis revealed AS was significantly associated with all oral health indicators (p < 0.05). Linear regression models showed apraxia is a predictor of GBI (p = 0.002) and CPITN (p = 0.027), but not of denture hygiene (p = 0.916). CONCLUSIONS: Although this pilot investigation has limitations, the results suggest the presence of apraxia should be considered when planning oral healthcare strategies. Further research with larger samples is encouraged to confirm these relationships.

[Communication training MultiTANDEMplus ­ A contribution to improve communication between professional caregivers and physicians]. / Kommunikationstraining MultiTANDEMplus - Ein Beitrag zur Verbesserung der Kommunikation zwischen Pflegenden und Ärzten.

BACKGROUND: Failures of communication between professional caregivers and physicians affect the quality of supply of nursing home residents. AIM: As part of a model project it was aimed to develop a training for caregivers to improve communication and promote cooperation with physicians. METHODS: For the needs assessment as a basis to develop the training 56 professional caregivers and 40 physicians engaged in nursing home care answered questionnaires regarding their cooperation. Based on these results a module for communication between professional caregivers and physicians was developed and adapted the TANDEM communication training for caregivers by Haberstroh and Pantel (2011). 25 professional caregivers in leading positions have been trained as multipliers in order to provide their colleagues the communication training with the additional element (TANDEMplus). TANDEMplus was evaluated in forms of reflection rounds and feedback questionnaires. RESULTS: 254 professional caregivers, housekeeping staff and daytime companions participated in a complete TANDEMplus training by the multipliers until July 2014. The implementation of their developed communication strategies into practice was experienced positively by the participants. CONCLUSIONS: The module "communication with physicians" is relevant for professional caregivers to raise awareness of their own competence and facilitate a structured information exchange at eye level. The training of multipliers was executed in order to ensure transfer effects and sustainability.

Cortical signature of neurological soft signs in recent onset schizophrenia.

Motor symptoms such as neurological soft signs (NSS) are characteristic phenomena of schizophrenia at any stage of the illness. Neuroimaging studies in schizophrenia patients have shown regional thinning of the cortical mantle, but it is unknown at present whether NSS are related to cortical thickness changes. Whole brain high-resolution magnetic resonance imaging at 3 Tesla was used to investigate cortical thickness in 28 patients with recent-onset schizophrenia. Cortical reconstruction was performed with the Freesurfer image analysis suite. NSS were examined on the Heidelberg Scale and related to cortical thickness. Age, education, and medication were considered as potential confounders. Higher NSS scores were associated with morphological changes of cortical thickness in multiple areas comprising paracentral gyrus, postcentral lobule, precuneus, inferior parietal lobule and temporal lobe. Our results confirm the hypothesis of a significant relationship between cortical thickness changes and the extent of NSS in schizophrenia. Investigation of cortical thickness may help to explain subtle motor symptoms such as NSS in schizophrenia.

Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease.

BACKGROUND: Evidence has emerged indicating that the ε4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD. METHODS: The aim of this study was to investigate interaction effects of the APOE ε4 allele and the alleles at the single-nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia. RESULTS: There was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE ε4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function. CONCLUSIONS: The data suggest a neural mechanism for APOE-PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE ε4 carriers.

The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

BACKGROUND: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-ß1-42 (Aß42), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD). METHODS: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). RESULTS: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/Aß42 ratio and 0.08 for the p-tau/Aß42 ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/Aß42 ratio. CONCLUSIONS: A tau/Aß42 ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.