Darren M. Lipnicki

Convergence of parvocellular and magnocellular information channels in the primary visual cortex of the macaque.

We investigated whether responses of single cells in the striate cortex of anaesthetized macaque monkeys exhibit signatures of both parvocellular (P) and magnocellular (M) inputs from the dorsal lateral geniculate nucleus (dLGN). We used a palette of 128 isoluminant hues at four different saturation levels to test responses to chromatic stimuli against a white background. Spectral selectivity with these isoluminant stimuli was taken as an indication of P inputs. The presence of magnocellular inputs to a given cortical cell was deduced from its responses to a battery of tests, including assessment of achromatic contrast sensitivity, relative strengths of chromatic and luminance borders in driving the cell at different velocities and conduction velocity of their retino‐geniculo‐cortical afferents. At least a quarter of the cells in our cortical sample appear to receive convergent P and M inputs. We cannot however, exclude the possibility that some of these cells could be receiving a convergent input from the third parallel channel from the dLGN, namely the koniocellular (K) rather than the P channel. The neurons with convergent P and M inputs were recorded not only from supragranular and infragranular layers but also from the principal geniculate input recipient layer 4. Thus, our results challenge classical ideas of strict parallelism between different information streams at the level of the primate striate cortex.

Factors Predicting Reversion from Mild Cognitive Impairment to Normal Cognitive Functioning: A Population-Based Study

Introduction Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition. Methods Our analyses considered 223 participants (48.9% male) aged 71–89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors. Results There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p = 0.026). Discussion Numerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of individuals with MCI. Participation in cognitively enriching activities and efforts to lower blood pressure might promote reversion.

Screening for dementia : a review of self-and informant-assessment instruments

BACKGROUND The objective of this study was to review available dementia screening instruments that could be recommended for self-administration, particularly in electronic format. Owing to the gradual loss of insight associated with the progression of dementia, a broad definition of self-administration including self-administration by concerned informants (family, friends, carers) was used. METHOD A systematic search of PubMed, PsychINFO, and the Cochrane Library Database was conducted. Only available full-text articles about dementia screening instruments written in English were included. Articles reporting on instruments used in a non-English context were excluded unless a validated English version of the instrument was available. Included instruments were assessed against the precise criteria and characteristics of the Mini-mental State Examination (MMSE), the most widely used screening instrument. RESULTS The Concord Informant Dementia Scale (CIDS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were the only instruments meeting all selection criteria. The Memory Impairment Screen (MIS) also met the criteria, although it lacks validation for self-administration. No instrument has been validated for self-administration in electronic format. CONCLUSIONS It is recommended that the MIS, the CIDS and the IQCODE be validated for self-administration in electronic format.

A longitudinal study of brain atrophy over two years in community-dwelling older individuals

Most previous neuroimaging studies of age-related brain structural changes in older individuals have been cross-sectional and/or restricted to clinical samples. The present study of 345 community-dwelling non-demented individuals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippocampus. In some regions, such as left and right entorhinal cortices, right hippocampus and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimers disease (AD).

Risk profiles of subtypes of mild cognitive impairment: the sydney memory and ageing study.

To compare the risk profiles of mild cognitive impairment (MCI) subtypes in a population‐based elderly sample.

Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

Introduction An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline. Methods Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined. Results All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine. Discussion Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.

Automated detection of amnestic mild cognitive impairment in community-dwelling elderly adults: a combined spatial atrophy and white matter alteration approach.

Amnestic mild cognitive impairment (aMCI) is a syndrome widely considered to be prodromal Alzheimers disease. Accurate diagnosis of aMCI would enable earlier treatment, and could thus help minimize the prevalence of Alzheimers disease. The aim of the present study was to evaluate a magnetic resonance imaging-based automated classification schema for identifying aMCI. This was carried out in a sample of community-dwelling adults aged 70-90 years old: 79 with a clinical diagnosis of aMCI and 204 who were cognitively normal. Our schema was novel in using measures of both spatial atrophy, derived from T1-weighted images, and white matter alterations, assessed with diffusion tensor imaging (DTI) tract-based spatial statistics (TBSS). Subcortical volumetric features were extracted using a FreeSurfer-initialized Large Deformation Diffeomorphic Metric Mapping (FS+LDDMM) segmentation approach, and fractional anisotropy (FA) values obtained for white matter regions of interest. Features were ranked by their ability to discriminate between aMCI and normal cognition, and a support vector machine (SVM) selected an optimal feature subset that was used to train SVM classifiers. As evaluated via 10-fold cross-validation, the classification performance characteristics achieved by our schema were: accuracy, 71.09%; sensitivity, 51.96%; specificity, 78.40%; and area under the curve, 0.7003. Additionally, we identified numerous socio-demographic, lifestyle, health and other factors potentially implicated in the misclassification of individuals by our schema and those previously used by others. Given its high level of performance, our classification schema could facilitate the early detection of aMCI in community-dwelling elderly adults.

The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%–36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%–10.8%); Clinical Dementia Rating of 0.5 (1.8%–14.9%); Mini-Mental State Examination score of 24–27 (2.1%–20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Risk profiles for mild cognitive impairment vary by age and sex: the Sydney Memory and Ageing study.

OBJECTIVES : To examine age- and sex-related differences in risk and protective factors for mild cognitive impairment (MCI) in community-based elderly individuals. DESIGN : Cross-sectional study. SETTING : The population-based Sydney Memory and Ageing Study. PARTICIPANTS : A total of 757 nondemented, community-dwelling elderly individuals from an English-speaking background categorized as younger (70-79 years) or older (80-90 years). MEASUREMENTS : Risk of MCI was determined for sociodemographic, lifestyle, and cardiac, physical, mental, and general health factors using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. RESULTS : The point prevalence of MCI within our sample was 39.1% overall: it was lowest in younger women (32.3%) and similar across men and older women (41.9%-43.6%). The risk of MCI across all participants was increased by the APOE ∊4 allele, high homocysteine, and heart disease; and decreased by better odor identification, visual acuity, and mental activity. Risk factors in all younger participants were slow 6-m walk, poor odor identification, and high homocysteine. Risk of MCI was associated in younger women with history of depression, less mental activity, slower 6-m walk, poorer visual acuity, and higher homocysteine; and in younger men with poorer odor identification and higher homocysteine. Older participants showed no significant risk factors for MCI, except for poorer visual acuity in men. Supporting these findings were statistically significant interactions that reflected the differences in risk factor profiles between age and/or sex groups. CONCLUSIONS : Risk factors for MCI differ in men and women and vary with age. This has implications for preventing MCI and possibly dementia.

Noradrenaline provokes axon reflex hyperaemia in the skin of the human forearm.

High doses of noradrenaline increase the sensitivity of skin to heat, presumably by sensitizing nociceptive afferent fibres. Since activation of these fibres increases local blood flow by an axon reflex mechanism, noradrenaline might simultaneously evoke adrenoceptor-mediated vasoconstriction and axon reflex vasodilatation. To investigate this possibility, noradrenaline was introduced into the skin of the human forearm by iontophoresis, and changes in blood flow were monitored in nearby skin. Increases in blood flow were greater near the site of noradrenaline iontophoresis than near the site of saline iontophoresis. Since the response was limited in its distribution to a few centimeters from the site of iontophoresis, hyperaemia was most likely due to a local mechanism rather than a spinal or supraspinal reflex. In addition, pretreatment of the skin with a local anaesthetic cream inhibited the increase in flow, indicating that the response was mediated neurally. These findings suggest that activation of nociceptive afferents by noradrenaline provokes axon reflex hyperaemia.