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Late-life participation in cognitively stimulating activities is thought to contribute to an individual's cognitive reserve and thus protect against cognitive decline, yet its association with clinical markers of neurodegeneration is not well established. To investigate, we developed a 13-item self-report "cognitively stimulating activities" questionnaire (CSA-Q), which was completed by a community sample of 269 older adults (>50 years) at risk of dementia. Participants met criteria for Mild Cognitive Impairment (MCI) and were classified as amnestic (aMCI; n = 93) or non-amnestic (naMCI; n = 176). Weighted CSA-Q dimensions were calculated for activity intensity, mental engagement and social engagement via a panel of 23 inter-raters. The CSA-Q mean and its dimensions were examined in relation to: (a) demographics (age, sex), (b) cognitive reserve proxies (years of education, premorbid IQ), (c) neuropsychological markers across cognitive domains of executive function, processing speed, learning, and memory storage, and (d) neuroimaging markers (left and right hippocampal volume). Analyses were conducted for all MCI, as well as for aMCI and naMCI sub-types. The CSA-Q was found to have concurrent validity with cognitive reserve proxies. Among all MCI, the CSA-Q dimensions of intensity and mental engagement had moderate associations with left hippocampal volume, but not with neuropsychological performance. For naMCI, the CSA-Q had moderate associations with left hippocampal volume, and small associations with aspects of executive functioning and processing speed. No equivalent associations emerged for the aMCI subtype. Our findings show that the CSA-Q may be particularly useful for older adults with non-amnestic cognitive deficits.

Major Depressive Disorder (MDD) is common and disabling, and is linked to functional impairment and increased mortality. While current treatments for MDD are moderately effective, ultimately, up to one third of patients do not achieve full remission. Interestingly, while affective symptoms of major depression typically resolve with the depressive episode, cognitive impairment frequently persists, and has been identified as one of the most prominent predictors of illness recurrence. Additionally, MDD is well-recognised as a key risk factor for further cognitive decline and dementia. Yet, available treatments for MDD do not typically address cognitive impairment. Cognitive training, represents a promising and novel therapeutic intervention in this regard. This review systematically identified and evaluated the evidence for cognitive training in adults with MDD. Following PRISMA guidelines, eligible studies were selected according to pre-defined criteria delineating our target population (adults with clinically defined MDD), parameters for cognitive training interventions (computer-or strategy-based, clinician-facilitated), and study design (controlled trials including pre-post cognitive and psychological or functional outcome data). Of 448 studies identified, nine studies met inclusion criteria. These studies were evaluated for methodological quality and risk of bias. Despite heterogeneity, qualitative and meta-analytic synthesis of study findings revealed significant improvements in cognitive and affective outcomes following cognitive training, with moderate pooled effect sizes. Unfortunately, very few studies investigated 'far transfer' to broader domains of everyday functioning. Overall, given the strong evidence for the efficacy and value of cognitive training in this context, cognitive training should be considered as a primary therapeutic intervention in the treatment of MDD.

Communicating personal Alzheimer’s disease risk profiles based on validated risk algorithms may improve public knowledge about risk reduction, and initiate action. This proof of concept pilot trial aimed to test whether this is feasible and potentially effective and/or harmful. Older at-risk adults (N=24) were provided with their personal Alzheimer’s disease risk profile online, which contained information on their personal risk level, scores and tailored recommendations to manage modifiable risk factors. After receiving the risk profile, participants were significantly more accurate in identifying risk and protective factors, and revised their perceived risk to be lower than their initial estimate. There was no apparent harm seen in psychological distress or dementia-related worry. This shows preliminary support for the feasibility of delivering personal dementia risk profiles to low risk, help-seeking older adults in an online format. A definitive trial examining behavioural outcomes and testing in groups with higher risk profiles is now warranted.

Objectives:Older adults presenting with mild cognitive impairment (MCI) have a higher risk of developing dementia and also demonstrate impairments in social cognition. This study sought to establish whether in people with MCI, poorer theory of mind (ToM) was associated with volumetric changes in the amygdala and hippocampus, as well as early changes in behaviour.Methods:One hundred and fourteen people with MCI and fifty-two older adult controls completed the Reading the Mind in the Eyes Test (RMET), while close informants (e.g., spouse/family member/friend/carer) described any current behavioural changes using the Revised Cambridge Behavioural Inventory (CBI-R). A subsample of participants completed structural magnetic resonance imaging (MRI).Results:The MCI group showed poorer performance on all neuropsychological tests administered, and moderate reductions on the RMET compared to the control group (d = .44), with greater reduction observed in those with amnestic compared to non-amnestic MCI (p = .03). While a robust correlation was identified between poorer RMET performance and smaller hippocampal volume in the control group (ρ = .53, p = .01), this relationship was not apparent in the MCI group (ρ = .21, p = .11). In the MCI group, poorer RMET performance was associated with poorer everyday skills (ρ = −.26, p = .01) assessed by the CBI-R.Conclusions:Our findings cross-validate previous reports that social cognitive deficits in ToM are a feature of MCI and also suggest that disruptions to broader neural networks are likely to be implicated. Furthermore, ToM deficits in MCI are associated with a decline in everyday skills such as writing or paying bills.

Background: Older adults living with amnestic mild cognitive impairment (aMCI) not only demonstrate impairments in Theory of Mind (ToM), relative to adults with non-amnestic MCI (naMCI), but are also at a higher risk of developing dementia. Objective: Our primary objective was to ascertain whether default mode network (DMN) functional connectivity was differentially associated with ToM abilities between MCI subgroups. Methods: Using functional magnetic resonance imaging, we investigated alterations in resting-state functional connectivity within the brain’s DMN in a sample of 43 older adults with aMCI (n = 19) and naMCI (n = 24), previously reported to demonstrate poorer ToM abilities. Results: Compared to naMCI, the aMCI subgroup revealed a significant association between poorer ToM performance and reduced functional connectivity between the bilateral temporal pole (TempP) and the left lateral temporal cortex (LTC) (LTC_L-TempP_L: b = –0.06, t(33) = –3.53, p = 0.02; LTC_L-TempP_R: b = –0.07,t(33) = –3.20, p = 0.03); between the right TempP and the dorsal medial prefrontal cortex (dMPFC) (b = –0.04, t(33) = –3.02, p = 0.03) and between the left and right TempP (b = –0.05, t(33) = –3.26, p = 0.03). In the naMCI subgroup, the opposite relationship was present between the bilateral TempP and the left LTC (Combined correlation: r = –0.47, p = 0.02), however, not between the right TempP and the dMPFC (r = –0.14, p = 0.51) or the left and right TempP (r = –0.31, p = 0.14). Conclusion: Our findings suggest that alterations in functional connectivity within the DMN involving temporal and frontal lobe regions are associated with ToM deficits in aMCI.

IntroductionMelatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysisThe study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and disseminationThis protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol versionV.8 15 October 2020.

No intervention exists that can stop or reverse the progression of symptoms in people with dementia; however, several nonpharmacological treatments, including cognitively oriented treatments (COTs) and physical activity (PA) treatments, have shown promise in relation to cognitive outcomes. This chapter summarizes the cognitive and associated functional limitations of people with dementia, discusses the nature of the main approaches to COTs, and provides an overview of the evidence in relation to cognitive training, cognitive rehabilitation and cognitive stimulation therapy, as well as physical activity treatments. Clinician knowledge, competence, and confidence, the appropriateness of the intervention for that person, person with dementia engagement, and care partner involvement should be considered when implementing interventions. Ethnoracial and cultural factors, pragmatic trials, combination treatments, and new technologies are areas of future development and treatment.

Study Objectives Cardiovascular autonomic dysfunction, as measured by short-term diurnal heart rate variability (HRV), has been reported in older adults with mild cognitive impairment (MCI). However, it is unclear whether this impairment also exists during sleep in this group. We, therefore, compared overnight HRV during sleep in older adults with MCI and those with subjective cognitive impairment (SCI). Methods Older adults (n = 210) underwent overnight polysomnography. Eligible participants were characterized as multi-domain MCI or SCI. The multi-domain MCI group was comprised of amnestic and non-amnestic subtypes. Power spectral analysis of HRV was conducted on the overnight electrocardiogram during non-rapid eye movement (NREM), rapid eye movement (REM), N1, N2, N3 sleep stages, and wake periods. High-frequency HRV (HF-HRV) was employed as the primary measure to estimate parasympathetic function. Results The MCI group showed reduced HF-HRV during NREM sleep (p = 0.018), but not during wake or REM sleep (p > 0.05) compared to the SCI group. Participants with aMCI compared to SCI had the most pronounced reduction in HF-HRV across all NREM sleep stages—N1, N2, and N3, but not during wake or REM sleep. The naMCI sub-group did not show any significant differences in HF-HRV during any sleep stage compared to SCI. Conclusions Our study showed that amnestic MCI participants had greater reductions in HF-HRV during NREM sleep, relative to those with SCI, suggesting potential vulnerability to sleep-related parasympathetic dysfunction. HF-HRV, especially during NREM sleep, may be an early biomarker for dementia detection.

OBJECTIVE This study aimed to investigate the relationship between obesity and oxidative stress in older adults at risk for dementia. It also aimed to explore the influence of physical activity on the relationship between obesity and oxidative stress in this at risk cohort. METHODS Older adults at risk for dementia underwent comprehensive medical, neuropsychological, and psychiatric assessment. At risk was defined as participants with subjective or mild cognitive impairment. Glutathione was assessed by magnetic resonance spectroscopy in the left hippocampus and the anterior and posterior cingulate cortex. Body mass index (BMI) was calculated and classified as healthy (BMI

Background Dementia prevalence is expected to increase substantially over the next few decades. Since there is currently no cure for dementia available, there is an urgent need for the early identification of individuals at high risk for dementia, so that primary and secondary prevention strategies can be implemented. Recently, the LIfestyle for BRAin health (LIBRA) index was developed as a new dementia risk algorithm. It specifically focuses on modifiable risk and protective factors that can be targeted in midlife. Objective The objective of this study was to evaluate the LIBRA index in relation to markers of cognitive functioning in a clinical, health-seeking sample of community-based older adults. Methods 484 participants (mean age 62.7 years) were recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney. Participants underwent comprehensive clinical and neuropsychological assessment and completed a self-report survey pack. Participants were rated via consensus as having either subjective cognitive complaints (SCC) or meeting criteria for mild cognitive impairment (MCI). The LIBRA score was calculated based on 11 available risk and protective factors. Results 65.4% of the sample met criteria for MCI. People with MCI showed a significantly higher LIBRA score compared to people with SCC. Furthermore, multiple cognitive domains, in particular executive functioning, were associated with a higher LIBRA score, with stronger correlations in people with MCI. Conclusion The LIBRA index might be a useful tool to determine lifestyle-attributable risk of cognitive decline in an older health-seeking population, including people with MCI.

Previous meta-analyses indicate that computerized cognitive training (CCT) is a safe and efficacious intervention for cognition in older adults. However, efficacy varies across populations and cognitive domains, and little is known about the efficacy of CCT in people with mild cognitive impairment or dementia.The authors searched Medline, Embase, PsychINFO, CINAHL, and CENTRAL through July 1, 2016, for randomized controlled trials of CCT in older adults with mild cognitive impairment or dementia. Overall cognition, individual cognitive domains, psychosocial function, and activities of daily living were pooled separately for mild cognitive impairment and dementia trials.The overall effect on cognition in mild cognitive impairment across 17 trials was moderate (Hedges' g=0.35, 95% CI=0.20-0.51). There was no evidence of publication bias or difference between active- and passive-controlled trials. Small to moderate effects were found for global cognition, attention, working memory, learning, and memory, with the exception of nonverbal memory, and for psychosocial functioning, including depressive symptoms. In dementia, statistically significant effects were found on overall cognition (k=11, g=0.26, 95% CI=0.01-0.52) and visuospatial skills, but these were driven by three trials of virtual reality or Nintendo Wii.CCT is efficacious on global cognition, select cognitive domains, and psychosocial functioning in people with mild cognitive impairment. This intervention therefore warrants longer-term and larger-scale trials to examine effects on conversion to dementia. Conversely, evidence for efficacy in people with dementia is weak and limited to trials of immersive technologies.

Cognitive impairment is now widely accepted as a fundamental aspect of Parkinson’s disease (PD). Given the prevalence of cognitive impairment and the associated impact on well-being, evidence-based interventions are needed. However, while research is continually accumulating in order to better understand the pathology and trajectory of cognitive changes, treatment options lag behind. Nonpharmacological approaches are of particular interest in this group, given the typical polypharmacy already present in PD patients. In this regard, cognitive training (CT) is a relatively new and prominent therapeutic option with accumulating scientific support and increasing public awareness. Research has now established benefits across many different populations, and trials investigating the use of CT specifically in PD are becoming more common. We offer a brief summary of CT and its efficacy in PD samples to date, as well as discuss areas requiring further exploration in this group. Crucially, we suggest that CT should be supported as a research priority in PD, given both proven and potential benefits as a noninvasive and well-tolerated behavioral intervention for cognitive impairment.

The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the Healthy Brain Aging (HBA) Clinic and diagnosed with aMCI (n = 38), naMCI (n = 84) or subjective memory complaints (SMC; n = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.

Major depressive disorders (MDD) are common and disabling, and are linked to functional impairment and increased mortality. While current treatments for MDD are moderately effective, ultimately up to one-third of patients do not achieve full remission. Interestingly, while affective symptoms of depression resolve with the resolution of a depressive episode, cognitive or neuropsychological impairment persists, and has been identified as one of the most prominent predictors of ongoing disability, reduced quality of life, and illness recurrence. Yet available treatments in MDD do not typically address neuropsychological dysfunction. Cognitive training, however, despite a small and heterogeneous evidence base, represents a promising and novel therapeutic intervention for neuropsychological impairment in MDD, which may yield neuropsychological, affective, and functional benefits.

Background A major gap exists internationally in providing support to maintain functional and social independence of older people with dementia living at home. This project evaluates a model of care that integrates evidence-based strategies into a person-centred interdisciplinary rehabilitation package: Interdisciplinary Home-bAsed Reablement Program (I-HARP). Two central aims are: 1) to determine the effectiveness of I-HARP on functional independence, mobility, quality of life and depression among people with dementia, their home environmental safety, carer burden and quality of life, and I-HARP cost-effectiveness; and 2) to evaluate the processes, outcomes and influencing factors of the I-HARP implementation. Methods I-HARP is a 4-month model of care, integrated in community aged care services and hospital-based community geriatric services, and consists of: 1) 8–12 home visits, tailored to the individual client’s needs, by an occupational therapist, registered nurse, and other allied health staff; 2) minor home modifications/assistive devices to the value of 60 years with mild to moderate dementia and his/her carer). During Phase I, I-HARP advisory group is established and training of I-HARP interventionists is completed, and the effectiveness of I-HARP is examined using a pragmatic RCT. Phase II, conducted concurrently with Phase I, focuses on the process evaluation of the I-HARP implementation using a realist approach. Semi-structured interviews with participants and focus groups with I-HARP interventionists and participating site managers will provide insights into the contexts, mechanisms and outcomes of I-HARP. Discussion I-HARP is being evaluated within the real-world systems of hospital-based and community-based aged care services in Australia. Future directions and strategies for reablement approaches to care for community dwelling people living with dementia, will be developed. The study will provide evidence to inform key stakeholders in their decision making and the use/delivery of the program, as well as influence future systems-thinking and changes for dementia care. Trial registration Australian New Zealand Clinical Trial Registry ACTR N12618000600246 (approved 18/04/2018).

Objectives: To test feasibility and potential effects of the interdisciplinary Home-bAsed Reablement Program (I-HARP) that integrates evidence-based strategies and cognitive rehabilitation techniqu...

Objectives:Disability in older adults is associated with a need for support in work, education, and community activities, reduced independence, and poorer quality of life. This study examines potential determinants of disability in a clinical sample of older adults across the continuum of cognitive decline, including sociodemographic, medical, psychiatric, and cognitive factors.Design:This is a cross-sectional study.Setting:Participants were recruited from a specialty clinic for adults “at risk” of or with early dementia (including subjective cognitive complaints, mild cognitive impairment, and early dementia).Participants:Four hundred forty-two older adults (mean age = 67.11, SD = 9.33) underwent comprehensive medical, neuropsychological, and mood assessments.Measurements:Disability was assessed via the self-report World Health Organization Disability Assessment Schedule 2.0. A stepwise (forward) linear regression model was computed to determine factors that contribute to disability within this group.Results:Depressive symptoms were the largest predictor, uniquely explaining 31.8% of the variance. Other contributing factors in the model included younger age, medical burden, and sleep quality, with all factors together accounting for a total of 50.4% of the variance in disability. Cognitive variables did not contribute to the model.Conclusions:Depressive symptoms account for a significant portion of the variance in disability, but other factors such as age, medical burden and sleep quality are also important contributors in older adults across the continuum of cognitive decline. The relative association of these variables with disability appears to differ for older (≥65 years) relative to younger (

Major depressive disorders (MDD) are common and disabling, and are linked to functional impairment and increased mortality. While current treatments for MDD are moderately effective, ultimately, up to one third of patients do not achieve full remission. Interestingly, while affective symptoms of depression resolve with the resolution of a depressive episode, cognitive impairment frequently persists, and has been identified as one of the most prominent predictors of illness recurrence. Additionally, MDD is well-recognised as a key risk factor for further cognitive decline and dementia. Yet, available treatments in MDD do not typically address cognitive impairment. Cognitive training (CT), represents a promising and novel therapeutic intervention in this regard. Our review systematically identified and quantitatively evaluated the evidence for CT in adults with MDD. Following PRISMA guidelines, eligible studies were selected according to pre-defined criteria delineating our target population (adults with clinically defined MDD), parameters for CT interventions (computer-or strategy-based, clinician-facilitated), and study design (controlled trials including pre/post cognitive and psychological or functional outcome data). Of 111 identified, nine studies met inclusion criteria. These studies were evaluated for methodological quality and risk of bias. Despite heterogeneity, qualitative and meta-analytic synthesis of study findings revealed significant improvements in cognitive and affective outcomes following CT, with pooled effect sizes ranging from moderate to large. Unfortunately, very few studies investigated ‘far transfer’ to broader domains of everyday functioning. Overall, given the strong evidence supporting the efficacy and value of CT in this context, CT should be considered as a primary therapeutic intervention in the holistic treatment of MDD.

Background:Current treatments for Major Depression are only moderately effective. In fact, 20-30% do not achieve full recovery despite multiple interventions. Interestingly, while it is well recognised that cognitive impairment is associated with Major Depression, available treatments do not address cognitive impairment. In this regard, cognitive training (CT) represents a promising intervention, however CT is not typically offered in public health settings.Aim:To evaluate the feasibility of a blinded, randomised controlled trial of group-based CT in a hospital sample of older adults with clinically significant depressive symptoms or history of a major depressive episode within the last five years, and in doing so, to adapt and translate research findings to the clinical setting.Methods:40 older adults, aged at least 65 years, with depression or a history of depression, and without dementia were randomly allocated to Club Connect, a 10-week group-based healthy brain ageing CT program, or a waitlist, treatment-as-usual control group. Baseline assessment including review by a psychogeriatrician and a brief neuropsychological assessment was completed within a fortnight of the intervention starting, and follow-up assessment was completed within a fortnight of the intervention ceasing. Primary outcomes included feasibility of trial design, tolerability of the intervention, and acceptability of random allocation and data collection procedures (as perceived by both participants and clinicians). We also examined the most sensitive clinical outcomes and measurement tools to inform larger scale trials.Significance:The current health, social and economic costs of late-life depression, especially in those with concomitant cognitive impairment, renders the holistic treatment of depression in older adults a public health priority. CT represents an efficacious therapeutic intervention in this regard, however, there appears to be a paucity of CT programs being offered in public health settings. This trial represents the first step in addressing the ‘implementation gap’ that exists between care that is known to be effective and care that is delivered. We must recognise the need to evaluate not only health outcomes, but also to perform formative evaluations that assess the extent to which implementation is effective in order to optimise intervention benefits, to prolong sustainability, and to promote dissemination of findings.

The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson’s disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks. The primary outcome was percentage of time spent frozen during a Timed Up and Go task, assessed both on and off dopaminergic medications. Secondary outcomes included multiple neuropsychological and psychosocial measures. A full analysis was first conducted on all participants randomized, followed by a sample of interest including only those who had objective FoG at baseline, and completed the intervention. Sixty-five patients were randomized into the study. The sample of interest included 20 in the CT group and 18 in the active control group. The primary outcome of percentage time spent frozen during a gait task was significantly improved in the CT group compared to active controls in the on-state. There were no differences in the off-state. Patients who received CT also demonstrated improved processing speed and reduced daytime sleepiness compared to those in the active control. The findings suggest that CT can reduce the severity of FoG in the on-state, however replication in a larger sample is required., Freezing of gait: a non-pharmacological approach Cognitive training can reduce the severity of gait freezing in Parkinson’s disease (PD) patients on dopaminergic medication. The inability to move forwards despite the intention to walk is one of the most debilitating symptoms in patients with PD and has been linked to cognitive dysfunction. Simon Lewis at the University of Sydney, Australia, and colleagues examined the effects of cognitive training in patients with self-reported freezing of gait and without dementia. Patients receiving cognitive therapy twice a week for seven weeks showed a significant reduction in gait freezing compared to the control group. Interestingly, the effect was observed when patients had maximum benefit from their PD medication (on-state) but not in the off-state. Cognitive training also improved patients’ processing speed and reduced their daytime sleepiness highlighting the usefulness of non-pharmacological interventions in the treatment of PD.

Research interest in sleep as a risk factor for dementia has grown, warranting an update in advances over the last 18 months, particularly in the mild cognitive impairment (MCI) stage in which interventions may be best targeted.The current systematic review includes empiric research articles published since 2016 that have investigated sleep (excluding obstructive sleep apnea) in MCI. Published articles include case-control studies, those examining clinical correlates of sleep problems, sleep microarchitecture, neuroimaging studies and novel cerebrospinal and blood-based markers.Evidence accumulated since 2016 continues to demonstrate that people with MCI manifest sleep disturbance on self-report measures. Neurophysiologically, sleep disturbance in MCI appears to be associated with diminished sleep spindles, key processes involved in overnight memory consolidation. Those with both MCI and sleep disturbance appear to have more pronounced functional connectivity alterations in temporoparietal brain regions and higher levels of the wake-promoting neurotransmitter orexin in cerebrospinal fluid than those with MCI alone. Novel findings also suggest that sleep may mediate homocysteine and oxidative stress mechanisms, warranting further exploration. Further studies focusing on novel interventions for sleep and circadian disturbance in MCI are warranted, particularly those targeting sleep spindles, orexin/hypocretin and the oxidative stress system.

Background: With the rise in the ageing population and absence of a cure for dementia, cost-effective prevention strategies for those 'at risk' of dementia including those with depression and/or mild cognitive impairment are urgently required. Objective: This study evaluated the efficacy of a multifaceted Healthy Brain Ageing Cognitive Training (HBA-CT) program for older adults 'at risk' of dementia. Methods: Using a single-blinded design, 64 participants (mean age = 66.5 years, SD = 8.6) were randomized to an immediate treatment (HBA-CT) or treatment-as-usual control arm. The HBA-CT intervention was conducted twice-weekly for seven weeks and comprised group-based psychoeducation about cognitive strategies and modifiable lifestyle factors pertaining to healthy brain ageing, and computerized cognitive training. Results: In comparison to the treatment-as-usual control arm, the HBA-CT program was associated with improvements in verbal memory (p = 0.03), self-reported memory (p = 0.03), mood (p = 0.01), and sleep (p = 0.01). While the improvements in memory (p = 0.03) and sleep (p = 0.02) remained after controlling for improvements in mood, only a trend in verbal memory improvement was apparent after controlling for sleep. Conclusion: The HBA-CT program improves cognitive, mood, and sleep functions in older adults 'at risk' of dementia, and therefore offers promise as a secondary prevention strategy. © 2015 IOS Press and the authors. All rights reserved.

Background: Using the Movement Disorder Society (MDS) Task Force Level 1 criteria, this study examined the classification of mild cognitive impairment in Parkinson's Disease (PD-MCI) derived from a range of cut-off scores that have previously been suggested by the MDS Task Force. Furthermore, differences in PD-MCI frequencies were examined when comparing performance on current neuropsychological testing to the normative sample, as opposed to decline from premorbid functioning, as evidence of cognitive impairment. Method: Two hundred and thirty-four non-demented PD patients underwent neurological and neuropsychological assessment at the Parkinson's Disease Research Clinic at the Brain and Mind Research Institute, University of Sydney. Results: When cognitive impairment was defined as 1SD and 1.5SD below premorbid intellect, 109 patients (47%) and 76 (32%) patients met criteria for PD-MCI respectively. This proportion dropped considerably to 50 patients (21%) with a 2SD cut-off score. However, when calculating impairment based on comparisons with normative data, only 68 patients (29%) and 41 patients (18%) met PD-MCI criteria when a cut-off score of 1 and 1.5SD was employed. This proportion dropped to just 22 patients (9%) with a 2SD cut-off score. Conclusion: Results from the present study suggest that the MDS PD-MCI criteria may be too broad, as substantial differences in frequencies of PD-MCI were observed with the application of differing criteria. We propose that a 1.5SD cut-off score below premorbid functioning may provide greater utility in characterizing PD-MCI than a 1.5SD cut-off below normative data, which has been widely applied in previous studies examining the MDS PD-MCI criteria.

Freezing of gait is a frequent and disabling symptom experienced by many patients with Parkinson's disease. A number of executive deficits have been shown to be associated with the phenomenon suggesting a common underlying pathophysiology, which as of yet remains unclear. Neuroimaging studies have also implicated the role of the cognitive control network in patients with freezing. To explore this concept, the current study examined error-monitoring as a measure of cognitive control. Thirty-four patients with and 38 without freezing of gait, who were otherwise well matched on disease severity, completed a colour-word interference task that allowed the specific assessment of error monitoring during conflict. Whilst both groups performed colour-naming and word-reading tasks equally well, those patients with freezing showed a pattern between conditions whereby they were better able to monitor performance and self-correct errors in the pure inhibition task but not after a switching rule was introduced. The novel results shown here provide insight into possible pathophysiological mechanisms involved in cognitive load and error monitoring in patients with freezing of gait. These results provide further evidence for the role of functional frontostriatal circuitry impairments in patients with freezing of gait and have implications for future studies and possible therapeutic interventions.

This study aimed to evaluate the efficacy of a multifactorial 'healthy brain ageing cognitive training program' for Parkinson's disease. Using a single-blinded waitlist control design, 50 participants with Parkinson's disease were recruited from the Brain & Mind Research Institute, Sydney, Australia. The intervention encompassed both psychoeducation and cognitive training; each component lasted 1-hour. The 2-hour sessions were delivered in a group format, twice-weekly over a 7-week period. Multifactorial psychoeducation was delivered by a range of health professionals. In addition to delivering cognitive strategies, it targeted depression, anxiety, sleep, vascular risk factors, diet, and exercise. Cognitive training was computer-based and was conducted by clinical neuropsychologists. The primary outcome was memory. Secondary outcomes included other aspects of cognition and knowledge pertaining to the psychoeducation material. Results demonstrated that cognitive training was associated with significant improvements in learning and memory corresponding to medium to large effect sizes. Treatment was also associated with medium effect size improvements in knowledge. Although the study was limited by the lack of randomized allocation to treatment and control groups, these findings suggest that a healthy brain ageing cognitive training program may be a viable tool to improve memory and/or slow cognitive decline in people with Parkinson's disease. It also appeared successful for increasing awareness of adaptive and/or compensatory cognitive strategies, as well as modifiable risk factors to optimize brain functioning.

Background: Recent attempts to standardise the definition of Mild Cognitive Impairment (MCI) in Parkinson s disease (PD) by the Movement Disorder Society Task Force has led to a greater understanding of this entity but to date, there has been a paucity of research regarding the impact of PD-MCI on caregiver outcomes. Objective: The aim of this study was to utilise the newly established PD-MCI diagnostic criteria to investigate caregiver outcomes in relation to four specific aspects: (1) caregiver burden, (2) quality of life (QoL), (3) caregiving experience, and (4) psychological distress. Methods: This study included a total of 166 patient-caregiver dyads. Caregiver outcomes including quality of life, caregiver burden, mood disturbances, and caregiver experience were compared between caregivers of PD patients classified as having normal cognition (PD-NC) and PD-MCI. Results: Despite the two groups being matched on demographic and clinical features, caregivers of PD-MCI patients reported a lower level of QoL with regard to physical health and more interruptions with usual activities. On the other hand, a higher impact on finances was reported in caregivers of PD-NC patients, relative to caregivers of PD-MCI patients. Conclusions: This study has shown that even at earlier stages of cognitive impairment, PD-MCI caregivers already experience elevated levels of distress in the role of providing care to their care-recipients. These findings highlight the need to include management of caregiver distress and associated sequelae alongside the management of PD-MCI patients, early on in the disease course.

BackgroundLearning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus.MethodEighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2,s.d.= 9.1 years) and 27 never-depressed control participants (mean age = 63.9,s.d.= 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods.ResultsDepressed subjects had smaller right anterior caudate (RAC) (t= 2.3,p= 0.026) and poorer memory compared to controls (t= 2.5,p< 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r= 0.3,p= 0.003) and older age (r= −0.46,p< 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (β= 0.25,t= 2.16,p= 0.033;β= 0.19,t= 1.71,p= 0.091).ConclusionsIn older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy (1H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain. METHODS: Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent 1H-MRS to derive levels of ACC GSH reported as a ratio to creatine (GSH/Cr). RESULTS:Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = -0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.05). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = -0.49, P = 0.015; set shifting: r = -0.43, P = 0.037). CONCLUSIONS: Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this possible modifiable risk factor in older persons is now warranted. Copyright© 2016 Associated Professional Sleep Societies, LLC. All rights reserved.

Given projected increases in dementia prevalence, emphasising earlier stages of cognitive impairment in older adults enables targeted early intervention strategies. Strategy-based cognitive training (SCT) is a remedial approach involving guidance and practice in compensatory techniques to improve cognition, including memory and attention. It may also be effective for improving executive functions (EF) integral to everyday tasks. This review systematically evaluates SCT effects on EF in older adults without dementia. Following PRISMA guidelines, we reviewed eligible trials according to pre-defined criteria, differentiating SCT from other cognitive interventions and stipulating total EF-focused intervention time, study design and target population (healthy older adults or mild cognitive decline). We then evaluated trials according to design, methodological quality and outcomes. Unfortunately, with too few studies in mild cognitive impairment, we refocused our review only on healthy older adults. Thirteen studies with 4120 participants in total were included, primarily targeting inductive reasoning. Despite heterogeneous study designs and SCT programs, 11/13 trials reported significant EF improvements, generally of moderate effect size (Hedges' g > 0.3). Four studies reported sustained benefits from one month to 10 years. There was some evidence of far transfer. We conclude that there is promising evidence for SCT as a targeted intervention for EF in healthy older adults and preliminary evidence for maintaining effects over time. Fewer trials have investigated far transfer (e.g. improved everyday functioning) or capacity to delay/prevent dementia, which are most relevant to clinical utility. Limitations include the inability to calculate effect sizes for four studies and absence of statistical meta-analysis.

As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.

Background: The use of informant rating scales in older adults at risk of dementia may assist with early detection and intervention strategies. This study aims to evaluate whether informants rate greater cognitive change in patients with mild cognitive impairment (MCI) compared to cognitively intact individuals, and to determine the relationship between informant ratings of cognitive change and neuropsychological performance.Methods: One hundred and nine health-seeking older adults underwent clinical and neuropsychological assessments, and informants completed the Cambridge Behavioral Inventory-Revised (CBI-R). Patients were rated according to MCI criteria, including amnestic and non-amnestic subtypes, or as being cognitively intact. CBI-R ratings were evaluated with respect to MCI diagnosis and neuropsychological performance.Results: Compared to cognitively intact individuals, informants rated patients with MCI as having significantly more change in overall functioning (p < 0.05) as well as in specific domains of memory and orientation (p < 0.01), everyday skills (p < 0.05), and motivation (p < 0.05), even after controlling for depressive symptom severity. In further analyses, the non-amnestic MCI subgroup only had more informant-rated mood changes compared to the amnestic subgroup. In relation to neuropsychological performance, informant ratings were related to poorer visual memory, verbal learning and memory, language, and psychomotor speed, with correlations ranging from –0.19 to –0.43 (p < 0.05).Conclusions: These findings indicate that informants are sensitive to subtle early cognitive change in individuals with MCI, and that their ratings are related to objectively measured neuropsychological performance. Thus, the CBI-R may be valuable in assisting early screening and intervention processes.

The concept of differing clinical phenotypes within Parkinson’s disease (PD) is well represented in the literature. However, there is no consensus as to whether any particular disease phenotype is associated with an increased risk of mild cognitive impairment (MCI) using the newly proposed Movement Disorders Society diagnostic criteria for this feature. To explore the expression of PD-MCI in relation to the heterogeneity of idiopathic PD. A cluster analysis incorporating a range of specific demographic, clinical and cognitive variables was performed on 209 patients in the early stages of PD (between Hoehn and Yahr stages I–III). Post hoc analyses exploring variables not included in the clustering solution were performed to interrogate the veracity of the subgroups generated. This study identified four distinct PD cohorts: a younger disease-onset subgroup, a tremor dominant subgroup, a non-tremor dominant subgroup, and a subgroup with rapid disease progression. The present study identified a differential expression of PD-MCI across these subgroups, with the highest frequency observed in the non-tremor dominant cluster. The non-tremor dominant subgroup was also associated with a higher prevalence of freezing of gait, hallucinations, daytime somnolence, and rapid eye movement sleep behavior disorder compared with other subgroups. This study confirms the existence of heterogeneity within the early clinical stages of PD and for the first time highlights the differential expression of PD-MCI using the newly defined diagnostic criteria for this feature. An improved understanding of PD-MCI and its clinical relationships may lead to an improved understanding of the pathophysiology underlying heterogeneity in PD. A subset of patients with Parkinson’s disease (PD) shows a higher frequency of mild cognitive impairment (MCI). Disease pathways underlying cognitive symptoms of PD are not well understood, making it difficult to determine which patients are at highest risk. Researchers in Australia led by Simon Lewis at the University of Sydney analyzed cognitive and other variables in 209 patients with early stage PD, using new diagnostic criteria proposed by the International Parkinson and Movement Disorder Society. The team confirmed that patients could be divided into four groups: younger onset, tremor dominant, non-tremor dominant (NTD), and rapid disease progression. The NTD subgroup showed the highest frequency of MCI (54%), combined with a higher prevalence of other symptoms. Improving understanding of MCI in PD may therefore help to identify patients who would benefit from dementia intervention strategies.

Freezing of gait is a poorly understood symptom of Parkinson's disease (PD) that is commonly accompanied by executive dysfunction. This study employed an antisaccade task to measure deficits in inhibitory control in patients with freezing, and to determine if these are associated with a specific pattern of grey matter loss using voxel-based morphometry. PD patients with (n = 15) and without (n = 11) freezing along with 10 age-matched controls were included. A simple prosaccade task was administered, followed by a second antisaccade task that required subjects to either look towards or away from a peripheral target. Behavioral results from the antisaccade task were entered as covariates in the voxel-based morphometry analysis. Patient and control groups performed equally well on the first task. However, patients with freezing were significantly worse on the second, which was driven by a specific impairment in suppressing their responses toward the target on the antisaccade trials. Impaired antisaccade performance was associated with grey matter loss across bilateral visual and fronto-parietal regions. These results suggest that patients with freezing have a significant deficit of inhibitory control that is associated with volume reductions in regions crucial for orchestrating both complex motor behaviors and cognitive control. These findings highlight the inter-relationship between freezing of gait and cognition and confirm that dysfunction along common neural pathways is likely to mediate the widespread cognitive dysfunction that emerges with this symptom.

Background: Interest in electronic health (eHealth) technologies to screen for and treat a variety of medical and mental health problems is growing exponentially. However, no studies to date have investigated the feasibility of using such e-tools for older adults with mild cognitive impairment (MCI) or dementia. Objective: The objective of this study was to describe patterns of Internet use, as well as interest in and preferences for eHealth technologies among older adults with varying degrees of cognitive impairment. Methods: A total of 221 participants (mean age=67.6 years) attending the Healthy Brain Ageing Clinic at the University of Sydney, a specialist mood and memory clinic for adults ≥50 years of age, underwent comprehensive clinical and neuropsychological assessment and completed a 20-item self-report survey investigating current technology use and interest in eHealth technologies. Descriptive statistics and Fisher exact tests were used to characterize the findings, including variability in the results based on demographic and diagnostic factors, with diagnoses including subjective cognitive impairment (SCI), MCI, and dementia. Results: The sample comprised 27.6% (61/221) SCI, 62.0% (137/221) MCI, and 10.4% (23/221) dementia (mean Mini-Mental State Examination=28.2). The majority of participants reported using mobile phones (201/220, 91.4%) and computers (167/194, 86.1%) routinely, with most respondents having access to the Internet at home (204/220, 92.6%). Variability was evident in the use of computers, mobile phones, and health-related websites in relation to sociodemographic factors, with younger, employed respondents with higher levels of education being more likely to utilize these technologies. Whereas most respondents used email (196/217, 90.3%), the use of social media websites was relatively uncommon. The eHealth intervention of most interest to the broader sample was memory strategy training, with 82.7% (172/208) of participants reporting they would utilize this form of intervention. Preferences for other eHealth interventions varied in relation to educational level, with university-educated participants expressing greater interest in interventions related to mood (P=.01), socialization (P=.02), memory (P=.01), and computer-based exercises (P=.046). eHealth preferences also varied in association, with diagnosis for interventions targeting sleep (P=.01), nutrition (P=.004), vascular risk factors (P=.03), and memory (P=.02). Conclusions: Technology use is pervasive among older adults with cognitive impairment, though variability was noted in relation to age, education, vocational status, and diagnosis. There is also significant interest in Web-based interventions targeting cognition and memory, as well as other risk factors for cognitive decline, highlighting the urgent need for the development, implementation, and study of eHealth technologies tailored specifically to older adults, including those with MCI and early dementia. Strategies to promote eHealth use among older adults who are retired or have lower levels of education will also need to be considered.

Freezing of gait (FOG) is a disabling motor symptom experienced by a large proportion of patients with Parkinson’s disease (PD). While it is known that FOG contributes to lower health-related quality of life (HRQoL), previous studies have not accounted for other important factors when measuring the specific impact of this symptom. The aim of this study was to examine FOG and HRQoL while controlling for other factors that are known to impact patient well-being, including cognition, motor severity, sleep disturbance and mood. Two hundred and three patients with idiopathic PD (86 with FOG) were included in the study. All patients were between Hoehn and Yahr stages I–III. A forced entry multiple regression model evaluating the relative contribution of all symptoms was conducted, controlling for time since diagnosis and current dopaminergic treatment. Entering all significantly correlated variables into the regression model accounted for the majority of variance exploring HRQoL. Self-reported sleep–wake disturbances, depressive and anxious symptoms and FOG were individually significant predictors. FOG accounted for the highest amount of unique variance. While sleep–wake disturbance and mood have a significant negative impact on HRQoL in PD, the emergence of FOG represents the most substantial predictor among patients in the earlier clinical stages of disease. This finding presumably reflects the disabling loss of independence and fear of injury associated with FOG and underlines the importance of efforts to reduce this common symptom.

Aims: To examine the rates and clinical characteristics of mild cognitive impairment (MCI) in older people with depressive symptoms and to determine the relative contribution of hippocampal volume and MCI to memory change. Method: One hundred and fifty-two participants with lifetime Major Depression and remitted or mild symptoms and 28 healthy controls underwent psychiatric and neuropsychological assessments. Magnetic resonance imaging was also conducted in a subset of the patients (n = 81) and healthy controls (n = 18). Results: MCI was diagnosed in 75.7% of the patients and was associated with increasing age, medical burden, vascular risk factors, later age of depression onset and smaller hippocampi. Multiple regression showed that both hippocampal volume and MCI diagnosis mediate memory performance in depression. Conclusions: MCI occurs in older adults with a history of depression and is not simply due to symptom severity. Memory change is linked to underlying hippocampal atrophy in this patient group.

Background: With predicted increases in dementia incidence, interventions targeting neuroplasticity and neuroprotection are required. Cognitive Training (CT) is an intervention which has been shown to improve aspects of cognition, but the pathophysiological mechanisms contributing to its efficacy are unknown. Objective: We aimed to explore the neurobiological correlates of CT using Mismatch Negativity (MMN), a neurophysiological marker of pre-attentive information processing, which in turn, is postulated to underpin higher-order cognitive processes. Methods: As part of a larger randomized controlled trial, forty 'at risk' (i.e., mild cognitive impairment or late-life depression) participants aged 51-79 years underwent neurophysiological, neuropsychological, and psychiatric assessments before and after a multi-faceted seven-week CT program or a 'treatment-as-usual' seven-week waitlist period. Results: The treatment group demonstrated significantly increased fronto-central MMN responses (p < 0.05), as well as improved phonemic verbal fluency (p < 0.05) and decreased self-rated memory difficulties (p < 0.05) following CT, in comparison to the waitlist control group. However, there were no significant correlations between enhanced MMN and cognitive/psychosocial outcomes. Conclusions: Results from this preliminary investigation indicate that CT is associated with enhanced neurophysiological mechanisms suggestive of improved pre-attentive processing, which may reflect alterations in underlying neurobiology. Further research is warranted to confirm these findings, to explicate whether CT is associated with restorative or compensatory neuroplastic processes and to determine whether MMN is a useful biomarker for treatment response. © 2014 - IOS Press and the authors. All rights reserved.

Freezing of gait (FOG) is a complex motor symptom of Parkinson's disease that manifests as an inability to generate effective gait, leading to a significant falls risk and a severe impact on quality of life. Research into effective treatment options has provided relatively limited benefits and is often hindered by substantial limitations. In this article, current treatment and research options are briefly discussed and a proposal for the further exploration of non-invasive therapeutic approaches is given. Recent advances in the literature continue to identify a pattern of selective executive dysfunction in patients with freezing of gait and such findings highlight a possible common underlying pathophysiology. Therefore, cognitive training is of particular interest as it may be able to improve executive processes thus reducing the manifestation of FOG. This article focuses on the existing evidence for such intervention strategies and proposes that targeted cognitive training may offer a novel treatment option for FOG that is worthy of an increased research focus.

With estimates of dementia expected to rise over the coming decades, there is interest in understanding the factors associated with promoting neuroprotection and limiting neurodegeneration. In this study, we examined the change in the volume of the hippocampus over a 2-month period in 34 older people “at risk” of cognitive decline (mean age = 66.8 years, 38% male). Factors that were examined included cognitive reserve, neuropsychological functioning, depression as well as a lifestyle (cognitive training) intervention. The results showed that over a 2-month period, increases in hippocampal size were associated with having higher premorbid intellect, greater occupational attainment, superior memory, and higher levels of functioning. Conversely, depression and disability were associated with decreases in hippocampal volume. Cognitive training was not associated with changes in hippocampal volume. These findings suggest that factors associated with cognitive reserve, cognition and depression may play an integral pathophysiological role in determining hippocampal volumes in “at-risk” older adults.

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal MMN was significantly associated with poorer verbal learning (r = 0.496; p < 0.01) and reduced left temporal MMN was significantly associated with increased self-reported disability (r = -0.419; p < 0.05). These results indicate that patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.

Depression in older people has been consistently linked with a variety of neurobiological brain changes. One measure of preattentive auditory processing, the mismatch negativity (MMN), has not been previously examined in late-life depression. This study examined MMN elicited by duration deviant stimuli in older people with lifetime depression, and explored its relationship with neuropsychological functioning and disability.Twenty-two older health-seeking patients (mean age=65.2 years) with lifetime major depressive disorder and twelve age and sex-matched control participants (mean age=64.6 years) completed detailed clinical and neuropsychological assessments and the WHO-DAS as a measure of disability. MMN amplitudes were elicited using a two-tone passive auditory oddball paradigm and measured at frontal (Fz), central (Cz) and temporal (left and right mastoid: M1 and M2, respectively) sites.Patients with depression demonstrated reduced mean MMN amplitude at temporal (M1, t=3.1, p0.01; M2, t=3.8, p0.01), but not fronto-central sites. Reduced temporal MMN amplitudes did not relate to depressive symptom severity, but were associated with reduced semantic fluency and greater self-rated functional disability.The contribution of depressive symptom 'state' and medications on MMN need to be considered.Reduced mean amplitudes of mastoid MMN in older patients with lifetime depression may reflect underlying brain changes. This preattentive marker relates to neuropsychological probes of frontotemporal circuits, and importantly, is associated with disability. Longitudinal analysis of MMN in this group will determine its predictive utility as a biomarker for ongoing cognitive decline and illness chronicity.