Mapping Cognitive Trajectories and Detecting Early Dementia Using the Mini-Mental State Examination Cognitive Charts: Application to the French Three-City Cohort.

The Cognitive Quotient (QuoCo) classification algorithm monitoring decline on age- and education-adjusted Mini-Mental State Examination (MMSE)-derived cognitive charts has proved superior to the conventionally-used cut-off for identifying incident dementia; however, it remains to be tested in different settings. Data were drawn from the Three-City Cohort to 1) assess the screening accuracy of the QuoCo, and 2) compare its performance to that of serial MMSE tests applying different cut-offs. For the QuoCo, sensitivity was 74.2 (95% CI: 71.4-76.8) and specificity 84.1 (83.6-84.7) and for the MMSE < 24, 64.1 (61.1-67.0) and 94.8 (94.4-95.1), respectively; whereas overall accuracy and sensitivity was highest for MMSE cut-offs <25 and <26. User-friendly charts for mapping cognitive trajectories over visits with an alert for potentially 'abnormal' decline can be of practical use and encourage regular monitoring in primary care where the <24 cut-off is still widely used despite its poor sensitivity.

It's all about cognitive trajectory: Accuracy of the cognitive charts-MoCA in normal aging, MCI, and dementia.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is an established cognitive screening tool in older adults. It remains unclear, however, how to interpret its scores over time and distinguish age-associated cognitive decline (AACD) from early neurodegeneration. We aimed to create cognitive charts using the MoCA for longitudinal evaluation of AACD in clinical practice. METHODS: We analyzed data from the National Alzheimer's Coordinating Center (9684 participants aged 60 years or older) who completed the MoCA at baseline. We developed a linear regression model for the MoCA score as a function of age and education. Based on this model, we generated the Cognitive Charts-MoCA designed to optimize accuracy for distinguishing participants with MCI and dementia from healthy controls. We validated our model using two separate data sets. RESULTS: For longitudinal evaluation of the Cognitive Charts-MoCA, sensitivity (SE) was 89%, 95% confidence interval (CI): [86%, 92%] and specificity (SP) 79%, 95% CI: [77%, 81%], hence showing better performance than fixed cutoffs of MoCA (SE 82%, 95% CI: [79%, 85%], SP 68%, 95% CI: [67%, 70%]). For current cognitive status or baseline measurement, the Cognitive Charts-MoCA had a SE of 81%, 95% CI: [79%, 82%], SP of 84%, 95% CI: [83%, 85%] in distinguishing healthy controls from mild cognitive impairment or dementia. Results in two additional validation samples were comparable. CONCLUSIONS: The Cognitive Charts-MoCA showed high validity and diagnostic accuracy for determining whether older individuals show abnormal performance on serial MoCAs. This innovative model allows longitudinal cognitive evaluation and enables prompt initiation of investigation and treatment when appropriate.

Validation and diagnostic accuracy of predictive curves for age-associated longitudinal cognitive decline in older adults.

BACKGROUND: The Mini-Mental State Examination continues to be used frequently to screen for cognitive impairment in older adults, but it remains unclear how to interpret changes in its score over time to distinguish age-associated cognitive decline from an early degenerative process. We aimed to generate cognitive charts for use in clinical practice for longitudinal evaluation of age-associated cognitive decline. METHODS: We used data from the Canadian Study of Health and Aging from 7569 participants aged 65 years or older who completed a Mini-Mental State Examination at baseline, and at 5 and 10 years later to develop a linear regression model for the Mini-Mental State Examination score as a function of age and education. Based on this model, we generated cognitive charts designed to optimize accuracy for distinguishing participants with dementia from healthy controls. We validated our model using a separate data set of 6501 participants from the National Alzheimer's Coordinating Center's Uniform Data Set. RESULTS: For baseline measurement, the cognitive charts had a sensitivity of 80% (95% confidence interval [CI] 75% to 84%) and a specificity of 89% (95% CI 88% to 90%) for distinguishing healthy controls from participants with dementia. Similar sensitivities and specificities were observed for a decline over time greater than 1 percentile zone from the first measurement. Results in the validation sample were comparable, albeit with lower sensitivities. Negative predictive value was 99%. INTERPRETATION: Our innovative model, which factors in age and education, showed validity and diagnostic accuracy for determining whether older patients show abnormal performance on serial Mini-Mental State Examination measurements. Similar to growth curves used in pediatrics, cognitive charts allow longitudinal cognitive evaluation and enable prompt initiation of investigation and treatment when appropriate.

[The engraving of pharmacopoeia between XVIth-XVIIIth Century]. / La pharmacopée et son illustration du XVIe au XVIIIe siècle.

The pharmacopea is mainly known like a book containing descriptions of drugs and preparations of medicines. During the XVIth-XVIIIth centuries, some of these books were illustrated with engraving frontispieces. This study shows the meaning of these pictures, the composition and the artists and the messages which are incorporated.

Late-onset-psychosis: cognition.

BACKGROUND: The objectives of the study were to characterize and compare the cognitive profile and natural evolution of patients presenting late-onset psychotic symptoms (LOPS: onset ≥ 50 years old) to those of elderly patients (≥ 50 years old) with life-long/early-onset schizophrenia (EOS: onset <40 years old). METHODS: Neuropsychological profiles of 15 LOPS patients were compared to those of 17 elderly EOS patients and to those of two control groups (n = 11/group). The evolution of the two patient groups was compared using an independent diagnostic consensual procedure involving a geriatric psychiatry physician/clinician and a neuropsychologist blinded to the initial psychiatric diagnosis. RESULTS: EOS presented significant memory and executive impairments when compared to controls but there was no significant difference between LOPS and their controls when age and education were taken into account. However, a detailed inspection of normative data suggests more executive impairments in LOPS than in EOS. The clinical judgment of experts was in favour of significant cognitive deficits with or without dementia in most LOPS (82.3%-94.1%) and EOS (80.0%-93.3%) patients. Regarding evolution, mild cognitive impairment (MCI) and vascular cognitive impairment (VCI) were the most common clinical diagnoses made by geriatric psychiatry physicians/clinicians for the LOPS (40%). In addition, 20% of LOPS versus 5.9% of EOS patients met the diagnostic criteria for dementia by consensus of the experts. Cerebral abnormalities were confirmed (CT scan; SPECT) in 73.3% of LOPS patients. CONCLUSION: The present results suggest cognitive deficits (mostly of executive functions) and vascular and neurodegenerative vulnerability in LOPS. Further studies with larger samples are needed to confirm the present findings.

Periodic inclusion of room-temperature-ferromagnetic metal phosphide nanoparticles in carbon nanotubes.

We demonstrate the use of sequential catalytic growth to encapsulate iron, nickel-iron, and iron-cobalt phosphide catalyst nanoparticles periodically along the entire lengths of carbon nanotubes. Investigations by local electron spectroscopies and electron diffraction reveal the compositions and crystal structures of the encapsulated particles. Significantly, high spatial resolution magnetic characterization using magnetic force microscopy and off-axis electron holography demonstrates that encapsulated iron-cobalt phosphide nanoparticles are ferromagnetic at room temperature, in accordance with the properties of bulk metal phosphides of the same structure and composition.

Relevant synthesis parameters for the sequential catalytic growth of carbon nanotubes.

Sequential catalytic growth provides an efficient tool for the synthesis of carbon nanotubes periodically inserted with catalyst nanoparticles. Several synthesis parameters were found crucial in order to induce this particular growth mechanism. The presence of phosphorus is required to form metal phosphide particles active for the formation of carbon nanotubes with a matchstick morphology. The metal composition (Ni/Fe ratio) and the carbon supply have no influence on the nanofilament type but strongly affect the nanotube yield. The synthesis temperature induces important changes on both the nanofilament type and yield, which are correlated with important transformations of the catalyst layer in terms of composition, particle size, and physical state.

The rostral migratory stream in adult squirrel monkeys: contribution of new neurons to the olfactory tubercle and involvement of the antiapoptotic protein Bcl-2.

The subventricular zone (SVZ) lying along the ependymal layer of lateral ventricle is known to generate neural progenitor cells throughout adulthood in specific areas of the mammalian brain. In rodents, the anterior region of the SVZ produces neuroblasts that migrate in chain toward the olfactory bulb along the so-called rostral migratory stream (RMS). In the present study, the organization of the RMS in a representative of New World primates - the squirrel monkey (Saimiri sciureus) - was studied by using bromodeoxyuridine (BrdU), a thymidine analogue that incorporates itself into the DNA of cells undergoing mitotic division. Double and triple immunofluorescence labelling with a confocal microscope served to visualize cells that expressed BrdU as well as molecular markers of neurogenesis. Numerous newborn (BrdU+) cells, many ensheated in glial (GFAP+) tubes, were scattered along the entire RMS in squirrel monkeys. Some of these BrdU+ cells expressed molecular markers for early committed neurons (TuJ1), postmitotic granular neuroblasts (TUC-4) or mature neurons (MAP-2, NeuN), and virtually all of them expressed the antiapoptotic protein Bcl-2. A significant number of BrdU+ cells were found to deviate from the main stream of the RMS. Instead of reaching the olfactory bulb, these cells migrated ventrally into the olfactory tubercle, where they expressed a mature neuronal phenotype (MAP-2). These findings reveal that the RMS in New World monkeys is mitotically robust and markedly extended and suggest that Bcl-2 might play a role in the survival and/or differentiation of newborn neurons destined to olfactory bulb and olfactory tubercle in primates.

Newly generated neurons in the amygdala and adjoining cortex of adult primates.

The subventricular zone remains mitotically active throughout life in rodents. Studies with tritiated thymidine, which is incorporated into the DNA of mitotic cells, have revealed that the rodent subventricular zone produces neuroblasts that migrate toward the olfactory bulb along the rostral migratory stream. A similar migratory stream has been documented in monkeys by using the thymidine analogue BrdUrd. The same approach showed that neurogenesis occurred in the dentate gyrus of adult primates, including humans. In the present study, experiments combining injections of BrdUrd and the dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine, with the immunostaining for molecular markers of neurogenesis (polysialylated neural cell adhesion molecule, beta-tubulin-III, collapsin response mediator protein-4, neuronal nuclear protein) in New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have revealed that new neurons are produced in the amygdala, piriform cortex, and adjoining inferior temporal cortex in adult primates. These newborn neurons expressed the antiapoptotic protein Bcl-2 and formed a more-or-less continuous pathway that extended from the tip of the temporal ventricular horn to the deep portion of the temporal lobe. The production of newborn neurons in the amygdala, piriform cortex, and inferior temporal cortex seems to parallel the continuing addition of neurons in the olfactory bulb. These two concomitant phenomena may ensure structural stability and functional plasticity to the primate olfactory system and temporal lobe.

Bcl-2 expression in thalamus, brainstem, cerebellum and visual cortex of adult primate.

Due to the functional importance of Bcl-2, which acts as an anti-apoptotic protein that also affects neural differentiation and adult neurogenesis, we undertook a detailed immunohistochemical study of the distribution of this protein in the brain of squirrel monkeys. The present study describes findings obtained at thalamic, brainstem, cerebellum and visual cortex levels, and the data are compared with our previous results gathered in the same species. At thalamic level, Bcl-2-positive neurons occur in anterior, rostral intralaminar, midline and lateral habenular nuclei. The protein is also expressed in several structures associated with the ventricular system, including the subventricular zone (SVZ), the subcommissural organ, and the periventricular grey at rostral and caudal tips of the fourth ventricle. At brainstem and cerebellar levels, Bcl-2-positive neurons occur in the dorsal raphe nucleus, inferior olivary complex, and in molecular and granular layers of the cerebellum. Finally, neurons of layer IV of the striate cortex display a very strong Bcl-2 immunoreactivity that contrasts with the poor labeling of neurons in adjacent parastriate and peristriate cortices. These finding suggests that Bcl-2 plays a role in the plasticity and structural maintenance of various structures in the primate brain and indicate that the mitotically active SVZ might be more extended along the rostrocaudal axis in primates than in rodents.