Melissa J. Slavin

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimers disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD‐I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre‐mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review.

Purpose of reviewTo provide a comprehensive review of diffusion tensor imaging in evaluating microstructural changes in the spectrum of cognitive decline from ageing to Alzheimers disease, in particular focusing on mild cognitive impairment. Recent findingsMild cognitive impairment represents a transition phase between normal ageing and early Alzheimers disease. Diffusion tensor imaging has emerged as a useful imaging modality that provides information about the structural integrity of tissue. In healthy ageing, diffusion tensor imaging abnormalities occur in the frontal regions, specifically the frontal white matter, anterior cingulum and the genu of the corpus callosum. Some studies report an anterior–posterior gradient change with greater abnormalities in the genu than the splenium of the corpus callosum and in the frontal than parietal white matter. In Alzheimers disease, diffusion tensor imaging abnormalities are concentrated in the posterior regions: the parahippocampal gyrus, temporal white matter, splenium of corpus callosum and posterior cingulum. In mild cognitive impairment, changes seem to parallel those in Alzheimers disease, with similar posterior regions showing abnormalities. SummaryDue to the similarities in diffusion tensor imaging findings in both mild cognitive impairment and Alzheimers disease, it is likely that diffusion tensor imaging has the potential to emerge as a useful clinical tool for early detection and monitoring of disease progression and treatment response in mild cognitive impairment/Alzheimers disease patients.

A multifactorial approach to understanding fall risk in older people

OBJECTIVE: To identify the interrelationships and discriminatory value of a broad range of objectively measured explanatory risk factors for falls.

The Sydney Memory and Ageing Study (MAS): methodology and baseline medical and neuropsychiatric characteristics of an elderly epidemiological non-demented cohort of Australians aged 70-90 years.

BACKGROUND The Sydney Memory and Ageing Study (Sydney MAS) was initiated in 2005 to examine the clinical characteristics and prevalence of mild cognitive impairment (MCI) and related syndromes, and to determine the rate of change in cognitive function over time. METHODS Non-demented community-dwelling individuals (N = 1037) aged 70-90 were recruited from two areas of Sydney, following a random approach to 8914 individuals on the electoral roll. They underwent detailed neuropsychiatric and medical assessments and donated a blood sample for clinical chemistry, proteomics and genomics. A knowledgeable informant was also interviewed. Structural MRI scans were performed on 554 individuals, and subgroups participated in studies of falls and balance, metabolic and inflammatory markers, functional MRI and prospective memory. The cohort is to be followed up with brief telephone reviews annually, and detailed assessments biannually. RESULTS This is a generally well-functioning cohort mostly living in private homes and rating their health as being better than average, although vascular risk factors are common. Most (95.5%) participants or their informants identified a cognitive difficulty, and 43.5% had impairment on at least one neuropsychological test. MCI criteria were met by 34.8%; with 19.3% qualifying for amnestic MCI, whereas 15.5% had non-amnestic MCI; 1.6% had impairment on neuropsychological test performance but no subjective complaints; and 5.8% could not be classified. The rate of MCI was 30.9% in the youngest (70-75) and 39.1% in the oldest (85-90) age bands. Rates of depression and anxiety were 7.1% and 6.9% respectively. CONCLUSIONS Cognitive complaints are common in the elderly, and nearly one in three meet criteria for MCI. Longitudinal follow-up of this cohort will delineate the progression of complaints and objective cognitive impairment, and the determinants of such change.

Discrete Neuroanatomical Networks Are Associated with Specific Cognitive Abilities in Old Age

There have been many attempts at explaining age-related cognitive decline on the basis of regional brain changes, with the usual but inconsistent findings being that smaller gray matter volumes in certain brain regions predict worse cognitive performance in specific domains. Additionally, compromised white matter integrity, as suggested by white matter hyperintensities or decreased regional white matter fractional anisotropy, has an adverse impact on cognitive functions. The human brain is, however, a network and it may be more appropriate to relate cognitive functions to properties of the network rather than specific brain regions. We report on graph theory-based analyses of diffusion tensor imaging tract-derived connectivity in a sample of 342 healthy individuals aged 72–92 years. The cognitive domains included processing speed, memory, language, visuospatial, and executive functions. We examined the association of these cognitive assessments with both the connectivity of the whole brain network and individual cortical regions. We found that the efficiency of the whole brain network of cortical fiber connections had an influence on processing speed and visuospatial and executive functions. Correlations between connectivity of specific regions and cognitive assessments were also observed, e.g., stronger connectivity in regions such as superior frontal gyrus and posterior cingulate cortex were associated with better executive function. Similar to the relationship between regional connectivity efficiency and age, greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions. For the first time, regional anatomical connectivity maps related to processing speed and visuospatial and executive functions in the elderly are identified.

The greyscales task: a perceptual measure of attentional bias following unilateral hemispheric damage

The two cerebral hemispheres in humans have been suggested to control contralaterally opposed attentional biases. These biases may be revealed by unilateral hemispheric damage, which often causes contralesional spatial neglect, particularly when the right hemisphere (RH) is affected. Subtle attentional biases have also been observed in normal observers in tasks requiring judgements of horizontal spatial extent, brightness, numerosity and size. Here, we examined attentional biases for judging the darker of two left-right mirror-reversed brightness gradients under conditions of free viewing (the greyscales task). We compared performances of patients with damage to the RH (n=78) and left hemisphere (LH; n=20) with those of normal controls (n=20). Controls showed a small but significant leftward bias, implying a subtle asymmetry favouring the RH. In contrast, RH and LH patients showed extreme rightward and leftward biases, respectively, both of which differed significantly from that of controls. For the patient groups, performance on clinical tests of neglect (cancellation and line bisection) did not predict their greyscales scores. Pathological biases were present in patients without clinical neglect or visual field defects, suggesting that the attentional bias measured by the greyscales task can be dissociated from clinical neglect and visual sensory loss. The greyscales task offers an efficient means of quantifying pathological attentional biases in unilateral lesion patients; it is easy to administer and score, and may be particularly useful for clinical trials of recovery and rehabilitation following stroke.

Mild cognitive impairment in a community sample: The Sydney Memory and Ageing Study

Mild cognitive impairment (MCI) is associated with an increased dementia risk. This study reports incidence of MCI subtypes, rates of progression to dementia, and stability of MCI classification.

The relationship of neuropsychological function to instrumental activities of daily living in mild cognitive impairment

While activities of daily living are by definition preserved in mild cognitive impairment (MCI), there is evidence of poorer instrumental activities of daily living (IADL) functioning in MCI compared to normal ageing. The aims of the present study were to examine differences in IADL between individuals with MCI and cognitively normal elderly, and to examine the relationships of IADL with cognitive functions.

Diffusion Tensor Imaging of the Posterior Cingulate is a Useful Biomarker of Mild Cognitive Impairment

OBJECTIVES Mild cognitive impairment (MCI) is recognized as a predementia state, but its definition is inconsistent and only 20%-30% develop dementia after 2 years. Biomarkers may help identify individuals at greatest risk of progressive decline. The authors examine a novel neuroimaging technique, diffusion tensor imaging (DTI) as a potential biomarker of MCI. DESIGN Cross-sectional prospective study. SETTING Subjects were recruited randomly using the electoral roll from two electorates in East Sydney, Australia. PARTICIPANTS A community-dwelling sample (N = 249) and age 70-90 years. MEASUREMENTS Screening to exclude dementia, comprehensive neuropsychiatric assessment, cognitive test battery, structural magnetic resonance imaging and DTI to obtain measures of fractional anisotropy (FA) and mean diffusivity (MD). MCI was diagnosed by standard criteria. RESULTS After controlling for age, sex, and years of education, the amnestic MCI (aMCI) group demonstrated microstructural pathology in the parahippocampal white matter, frontal white matter, splenium of corpus callosum, and posterior cingulate region. The nonamnestic MCI (naMCI) group demonstrated microstructural pathology in the frontal white matter, internal capsule, occipital white matter, and the posterior cingulate region. A binary logistic regression model showed that DTI of the left posterior cingulate was significant in identifying persons with aMCI to an accuracy of 85.1%. Receiver operating characteristics curve analysis yielded a sensitivity of 80% and specificity of 60.3% in distinguishing aMCI from naMCI and the normal comparison group. CONCLUSION DTI of the posterior cingulate region discriminates MCI from cognitively normal individuals with accuracy and has the potential to be used as a biomarker of MCI, in particular aMCI.

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.