Normal aging and executive functions in "old-old" community dwellers: poor performance is not an inevitable outcome

BACKGROUND: Studies on normal aging and cognitive functioning commonly describe early and more pronounced age-related changes in executive functions (EFs) compared to other cognitive abilities. Two of the three most common neurodegenerative disorders associated with aging (vascular dementia [VaD] and extrapyramidal [EP]-related dementia) show executive dysfunctions in their clinical presentation; and these cognitive deficits are not uncommon in the third one: Alzheimer's disease (AD). METHODS: Nine EF tests (yielding 12 measures) were administered to 123 randomly selected community dwellers, aged 81 years and over, with the view to determine the effect of age on performance. Markers of AD, VaD, and EP-related dementia, as well as sociodemographic and psychological variables, were selected and their contribution to EF performance was investigated. RESULTS: Multiple linear regression analyses revealed the greatest contribution to EF scores from the markers of AD and estimated IQ but not from the markers of VaD and EP-related dementia or from age. CONCLUSIONS: These findings suggest that chronological age acts as a proxy variable mediating the impact of other factors such as subclinical signs of neurodegenerative disorders and that it has little independent contribution to make. They also indicate the importance of cognitive abilities supported by posterior cortical circuits in EF problem resolution. This study demonstrates that cognitive decline is not an ineluctable process that is associated with "normal" aging but rather represents, in many cases, a byproduct of neurodegenerative disorders, albeit themselves highly age-related.     

Cerebral organization in a right-handed trilingual patient with right-hemisphere speech: a positron emission tomography study

Using the method of positron emission tomography, combined with word-generation tasks, we had the opportunity to examine the cerebral representation of multiple languages in the brain in a right-handed patient, RA, with known right-hemisphere speech representation as determined by intracarotid sodium amobarbital testing. Similar patterns of cerebral blood flow were observed across all three languages (French, Spanish and English), when synonym generation was compared with a silent resting baseline. In particular, several regions in the right inferior frontal cortex were activated. These foci are in locations corresponding to those observed in the left hemisphere in normal right-handed volunteers with presumed left-hemisphere dominance, and in patients known to be left-hemisphere dominant for speech. The lack of anatomical separation of the three languages within the same individual, who acquired two languages early and one language later in life, suggests that at least at this single-word level of analysis, age of acquisition was not a significant factor in the determining of functional organization in the brain.     

Neuropsychological characteristics of adults with ADHD: a comprehensive review of initial studies

The role of neuropsychological evaluation in the diagnosis of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) is a growing area of research and clinical interest. Our review of the literature indicates that adults with ADHD demonstrate subtle impairments on select measures of attention and executive functions, auditory-verbal list learning, and complex information processing speed relative to normal controls. The validity of these findings is nonetheless hampered by several limitations, including methodological and sample variability, a restricted range of interpretive techniques, and uncertain discriminant validity. Recommendations are offered to advance the cognitive and neurobehavioral understanding of this disorder and to enhance the utility of neuropsychological methods for diagnosis and management of adults with ADHD.     

Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses

The purpose of this study was to document the accuracy of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) with sodium iodide detectors in characterizing indeterminate lung nodules or masses and in identifying additional extra-lesional findings. 50 consecutive patients without a confident diagnosis of malignancy on CT underwent (18)FDG PET with and without attenuation correction. The diagnosis of malignancy was made using visual diagnostic criteria, and tumour-to-blood pool ratios were calculated. The final diagnosis was established by surgery, biopsy or long-term follow-up. Any additional findings made at PET were recorded and similarly verified. Using blinded visual diagnostic criteria for the differentiation of malignant from benign nodules, sodium iodide PET achieved a sensitivity of 91% (30 of 33 cases), a specificity of 88% (15 of 17 cases), a positive predictive value for malignancy of 94% (30 of 32 cases) and a negative predictive value of 83% (15 of 18 cases). False positives occurred with active tuberculosis and sarcoidosis. False negatives were a 3 cm bronchoalveolar carcinoma, a 1.3 cm sarcoma metastasis and a 1 cm carcinoma. Use of tumour-to-blood pool ratios did not improve performance. PET suggested the presence of nodal or distant metastases in 13 of 33 patients with a malignant pulmonary lesion. These PET findings were confirmed in 11 patients. These results indicate that sodium iodide PET is an accurate tool for the characterization of indeterminate pulmonary masses or nodules and simultaneously provides non-invasive staging information that can alter patient management in up to one-third of such patients. Performance of sodium iodide PET is comparable with reported results for PET scanners using other detector materials.     

Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons

Stathmin is a ubiquitous cytosolic phosphoprotein, preferentially expressed in the nervous system, and the generic element of a protein family that includes the neural-specific proteins SCG10, SCLIP, and RB3 and its splice variants, RB3' and RB3". All phosphoproteins of the family share with stathmin its tubulin binding and microtubule (MT)-destabilizing activities. To understand better the specific roles of these proteins in neuronal cells, we performed a comparative study of their expression, regulation, and intracellular distribution in embryonic cortical neurons in culture. We found that stathmin is highly expressed ( approximately 0.25% of total proteins) and uniformly present in the various neuronal compartments (cell body, dendrites, axon, growth cones). It appeared mainly unphosphorylated or weakly phosphorylated on one site, and antisera to specific phosphorylated sites (serines 16, 25, or 38) did not reveal a differential regulation of its phosphorylation among neuronal cell compartments. However, they revealed a subpopulation of cells in which stathmin was highly phosphorylated on serine 16, possibly by CaM kinase II also active in a similar subpopulation. The other proteins of the stathmin family are expressed about 100-fold less than stathmin in partially distinct neuronal populations, RB3 being detected in only about 20% of neurons in culture. In contrast to stathmin, they are each mostly concentrated at the Golgi apparatus and are also present along dendrites and axons, including growth cones. Altogether, our results suggest that the different members of the stathmin family have complementary, at least partially distinct functions in neuronal cell regulation, in particular in relation to MT dynamics.     

Long-term fate of human telencephalic progenitor cells grafted into the adult mouse brain: effects of previous amplification in vitro

We assessed the developmental potential of human telencephalic progenitor cells, with and without previous amplification in vitro, following grafting into the nonlesioned adult mouse CNS. Cell suspensions, shown to contain neuroepithelium-like and neuroblast-like cells, were injected into the subventricular zone (SVZ) and the striatum. These two regions were selected for comparative studies because one, the SVZ, is mitotically active, whereas the other, the striatum, is mitotically inactive. In situ hybridization with a human-specific Alu probe showed that the cells survived for up to 30 weeks in both targets and migrated away from the injection site. Fresh cells continued to proliferate and gave rise to very extended grafts before differentiating into neurons and glia. We further show that, when grown in vitro prior to grafting, human cells acquired new properties: Their proliferation was very limited, and they differentiated more rapidly. This study therefore provides new information about the use of these cells, which are a potential tool for both cellular and gene therapy.     

Adult attachment style. II: Its relationship to psychosocial depressive-vulnerability

Background A range of studies show adult attachment style is associated with depressive-vulnerability factors such as low self-esteem, poor support and childhood adversity. However, there is wide inconsistency shown in the type of insecure style most highly associated. Few studies have examined attachment style in relation to clinical depression together with a range of such factors in epidemiological series. The present study uses an interview measure of adult attachment which differentiates type of attachment style and degree of insecurity of attachment, to see: (a) if it adds to other vulnerability in predicting depression and (b) if there is specificity of style to type of vulnerability. Method Two hundred and twenty-two high-risk and 80 comparison women were selected from questionnaire screenings of London GP patient lists and intensively interviewed. The Attachment Style Interview (ASI) differentiated five styles (Enmeshed, Fearful, Angry-dismissive, Withdrawn and Standard) as well as the degree to which attitudes and behaviour within such styles were dysfunctional (‘non-standard’). Attachment style was examined in relation to low self-esteem, support and childhood experience of neglect or abuse, and all of these examined in relation to clinical depression in a 12-month period. Results The presence of any ‘non-standard’ style was significantly related to poor support, low self-esteem and childhood adversity. Some specificity of type of style and type of vulnerability was observed. Logistic regression showed that non-standard Enmeshed, Fearful and Angry-dismissive styles, poor support and childhood neglect/abuse provided the best model for clinical depression. Conclusion Non-standard attachment in the form of markedly Enmeshed, Fearful or Angry-dismissive styles was shown to be associated with other depressive-vulnerability factors involving close relationships, self-esteem and childhood adversity and added to these in modelling depression. Accepted: 21 September 2001     

Metabotropic glutamate receptor 2/3-dependent long-term depression in the nucleus accumbens is blocked in morphine withdrawn mice

The nucleus accumbens (NAc) plays a crucial role in addiction. We have recently shown that activation of presynaptic metabotropic glutamate 2/3 receptors (mGlu2/3) induces long-term depression (LTD) at glutamatergic synapses in the mouse nucleus accumbens (NAc) through the long lasting inhibition of P/Q-type Ca2+ channels and the cAMP/protein kinase A (PKA) pathway. Because presynaptic mGlu2/3 functions are augmented in the ventral tegmental area of morphine-withdrawn rats, we have evaluated the consequences of opiate treatment on mGlu2/3 LTD at prelimbic NAc glutamatergic synapses. Here we report that mGlu2/3 LTD is abolished after 1 week of withdrawal from chronic morphine treatment; in the morphine-withdrawn group LTD measured 5.99 +/- 4.84% (P < 0.05) compared with 21.13 +/- 5.42% in the sham group. In contrast, chronic morphine treatment did not alter the mechanisms normally underlying mGlu2/3 LTD, such as the cAMP/PKA pathway or P/Q-type Ca2+ channels. This study shows that one long-term consequence of morphine treatment is an alteration of synaptic plasticity at glutamatergic synapses in the NAc. Considering that mGlu2/3 agonists (e.g. LY-354740 used in the present study to induce LTD) reduce behavioural symptoms of morphine withdrawal, these findings could be important in the understanding of the cellular events underlying the dependence-inducing properties of opiates.     

Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations

To gain a greater insight into the relationship between hyperactivity of the corticotropin-releasing hormone (CRH) system and autonomic and physiological changes associated with chronic stress, we developed a transgenic mouse model of central CRH overproduction. The extent of central and peripheral CRH overexpression, and the amount of bioactive CRH in the hypothalamus were determined in two lines of CRH-overexpressing (CRH-OE) mice. Furthermore, 24 h patterns of body temperature, heart rate, and activity were assessed using radiotelemetry, as well as cumulative water and food consumption and body weight gain over a 7-day period. CRH-OE mice showed increased amounts of CRH peptide and mRNA only in the central nervous system. Despite the presence of the same CRH transgene in their genome, only in one of the two established lines of CRH-OE mice (line 2122, but not 2123) was overexpression of CRH associated with increased levels of bioactive CRH in the hypothalamus, increased body temperature and heart rate (predominantly during the light (inactive) phase of the diurnal cycle), decreased heart rate variability during the dark (active) phase, and increased food and water consumption, when compared with littermate wildtype mice. Because line 2122 of the CRH transgenic mice showed chronic stress-like neuroendocrine and autonomic changes, these mice appear to represent a valid animal model for chronic stress and might be valuable in the research on the consequences of CRH excess in situations of chronic stress.     

Functional topography of the low postcentral area

OBJECT: The goal of this study was to establish a reliable method for identification of face and tongue sensory function in the lower central area. METHODS: All positron emission tomography (PET) clinical activation studies performed over a 3-year period at the Montreal Neurological Institute and Hospital were evaluated by coregistering the PET images with three-dimensional reconstructions of magnetic resonance images obtained in the same patients. In addition to stereotactic coordinates and measurements based on distance from the sylvian fissure, gyral and sulcal landmarks were analyzed to determine their reliability in localizing the sensory areas of the tongue and lower face. The convolutional anatomy of the central area is an important guide to the identification of function. The sensory area of the tongue is recognized as a triangular region at the base of the postcentral gyrus; the sensory area of the lower face resides in the narrowed portion of the postcentral gyrus, immediately above the tongue area. CONCLUSIONS: Cortical landmarks such as the substrata of tongue and face sensory impressions are more reliable guides than stereotactic coordinates or measurements for localizing function.