Managing comorbid cognitive impairment and hearing loss in older adults: a UK survey of audiology and memory services.

BACKGROUND: midlife hearing loss is a potentially modifiable risk factor for dementia. Addressing comorbid hearing loss and cognitive impairment in services for older adults may offer opportunities to reduce dementia risk. OBJECTIVE: to explore current practice and views amongst UK professionals regarding hearing assessment and care in memory clinics and cognitive assessment and care in hearing aid clinics. METHODS: national survey study. Between July 2021 and March 2022, we distributed the online survey link via email and via QR codes at conferences to professionals working in National Health Service (NHS) memory services and audiologists working in NHS and private adult audiology services. We present descriptive statistics. RESULTS: 135 professionals working in NHS memory services and 156 audiologists (68% NHS, 32% private sector) responded. Of those working in memory services, 79% estimate that >25% of their patients have significant hearing difficulties; 98% think it useful to ask about hearing difficulties and 91% do so; 56% think it useful to perform a hearing test in clinic but only 4% do so. Of audiologists, 36% estimate that >25% of their older adult patients have significant memory problems; 90% think it useful to perform cognitive assessments, but only 4% do so. Main barriers cited are lack of training, time and resources. CONCLUSIONS: although professionals working in memory and audiology services felt addressing this comorbidity would be useful, current practice varies and does not generally address it. These results inform future research into operational solutions to integrating memory and audiology services.

Adaption and preliminary validation of the Addenbrooke's Cognitive Examination-III as a screening test for mild cognitive impairment and dementia in hearing-impaired individuals.

BACKGROUND: A large proportion of older adults assessed for cognitive impairment likely have hearing loss, potentially affecting accuracy of cognitive performance estimations. This study aimed to develop a hearing-impaired version of the Addenbrooke's Cognitive Examination-III (HI-ACE-III) and to assess whether the HI-ACE-III can accurately distinguish people with mild cognitive impairment (MCI) and dementia from cognitively intact controls. METHODS: The HI-ACE-III was developed by converting verbal instructions into a visual, timed PowerPoint presentation. Seventy-four participants over the age of 60 years were classified into three groups: 29 had MCI, 15 had mild to moderate dementia and 30 were cognitively intact controls. Receiver operating characteristic (ROC) curves were graphed to test screening accuracy. Concurrent validity was examined through correlations between HI-ACE-III domain scores and relevant, visually presented standardized neuropsychological measures. RESULTS: ROC analysis for dementia revealed an area under the curve (AUC) of 0.99, achieving excellent sensitivity (100%) and good specificity (93.3%) at an optimum cut-off of <87. The AUC for MCI was 0.86, achieving reasonable sensitivity (75.9%) and good specificity (86.7%) at an optimum cut-off of <92. HI-ACE-III subtests shared anticipated and statistically significant correlations with established measures of cognitive functioning. Internal consistency of the HI-ACE-III was excellent as verified with Cronbach's alpha (α = 0.904). CONCLUSIONS: Preliminarily, the HI-ACE-III showed good reliability, validity and screening utility for MCI and dementia in older adults in a hearing-impairment context. The adapted HI-ACE-III may offer accurate and reliable indication of cognitive performance, supporting timely diagnosis and research examining links between hearing loss and cognitive decline.

Hearing-impaired population performance and the effect of hearing interventions on Montreal Cognitive Assessment (MoCA): Systematic review and meta-analysis.

BACKGROUND: Older adults are at high risk of developing age-related hearing loss (HL) and/or cognitive impairment. However, cognitive screening tools rely on oral administration of instructions and stimuli that may be impacted by HL. This systematic review aims to investigate (a) whether people with HL perform worse than those without HL on the Montreal Cognitive Assessment (MoCA), a widely used screening tool for cognitive impairment, and what the effect size of that difference is (b) whether HL treatment mitigates the impact of HL. METHOD: We conducted a systematic review and meta-analysis including studies that reported mean MoCA scores and SDs for individuals with HL. RESULTS: People with HL performed significantly worse on the MoCA (4 studies, N = 533) with a pooled mean difference of -1.66 points (95% confidence interval CI -2.74 to -0.58). There was no significant difference in MoCA score between the pre- vs post-hearing intervention (3 studies, N = 75). However, sensitivity analysis in the cochlear implant studies (2 studies, N = 33) showed improvement of the MoCA score by 1.73 (95% CI 0.18 to 3.28). CONCLUSION: People with HL score significantly lower than individuals with normal hearing on the standard orally administered MoCA. Clinicians should consider listening conditions when administering the MoCA and report the hearing status of the tested individuals, if known, taking this into account in interpretation or make note of any hearing difficulty during consultations which may warrant onward referral. Cochlear implants may improve the MoCA score of individuals with HL, and more evidence is required on other treatments. J Am Geriatr Soc 68:-, 2020.

The impact of sleep disturbances on care home residents with dementia: the SIESTA qualitative study.

OBJECTIVES: Nearly 40% of care home residents who are living with dementia also have symptoms of disturbed sleep. However, the impact of these disturbances is relatively unknown and is needed to indicate whether interventions are warranted; therefore, we aimed to investigate the impact. DESIGN: One-to-one semi-structured interviews. SETTINGS: Four UK care homes. PARTICIPANTS: We interviewed 18 nurses and care assistants about residents with sleep disturbances. MEASUREMENTS: We used a topic guide to explore staff experience of sleep disturbance in residents with dementia. The interviews were audio recorded and transcribed and then analyzed thematically by two researchers independently. RESULTS: Staff described that sleep disturbances in most, but not all, residents impacted negatively on the resident, other residents, staff, and relatives. Residents became more irritable or agitated if they had slept badly. They slept in the daytime after a bad night, which then increased their chances of being awake the following night. For some, being sleepy in the day led to falls, missing medication, drinks, and meals. Staff perceived hypnotics as having low efficacy, but increasing the risk of falls and drowsiness. Other residents were disturbed by noise, and staff described stress when several residents had sleep disturbance. Some of the strategies reported by staff to deal with sleep disturbances such as feeding or providing caffeinated tea at night might be counterproductive. CONCLUSIONS: Sleep disturbances in care home residents living with dementia negatively affect their physical and psychological well-being. These disturbances also disturb other residents and increase stress in staff.

Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients.

BACKGROUND: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes. AIMS: We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes. METHOD: Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term. RESULTS: Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021). CONCLUSIONS: Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia.

Bringing memory fMRI to the clinic: comparison of seven memory fMRI protocols in temporal lobe epilepsy.

fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation (P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients.

Modulatory effects of brain-derived neurotrophic factor Val66Met polymorphism on prefrontal regions in major depressive disorder.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to the development of depression (major depressive disorder, MDD), but it is unclear whether neural effects observed in healthy individuals are sustained in MDD. AIMS: To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions. METHOD: Magnetic resonance imaging scans were acquired in 79 persons with MDD (mean age 49 years) and 74 healthy volunteers (mean age 50 years). Effects on surface area and cortical thickness were examined with multiple comparison correction. RESULTS: People who were Met allele carriers showed reduced caudal middle frontal thickness in both study groups. Significant interaction effects were found in the anterior cingulate and rostral middle frontal regions, in which participants in the MDD group who were Met carriers showed the greatest reduction in surface area. CONCLUSIONS: Modulatory effects of the BDNF Val66Met polymorphism on distinct subregions in the prefrontal cortex in MDD support the neurotrophin model of depression.

Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine.

BACKGROUND: Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. METHODS: Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI. RESULTS: A significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response. CONCLUSIONS: Baseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation. TRIAL REGISTRATION: Registered at clinicaltrials.gov ( NCT01051466 ).

Predictive neural biomarkers of clinical response in depression: a meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies.

We performed a systematic review and meta-analysis of neural predictors of response to the most commonly used, evidence based treatments in clinical practice, namely pharmacological and psychological therapies. Investigations of medication-free subjects suffering from a current major depressive episode who underwent positron emission tomography (PET) or functional or structural magnetic resonance imaging (MRI) scans prior to the initiation of treatment were reviewed. Results of 20 studies from 15 independent samples were included in the functional imaging meta-analysis and 9 studies from 6 independent samples in the structural neuroimaging meta-analysis. Regional activations with prognostic value include the well replicated finding that increased baseline activity in the anterior cingulate is predictive of a higher likelihood of improvement. As well, increased baseline activation in the insula and striatum is associated with higher likelihood of a poorer clinical response. Structural neuroimaging studies indicated that a decrease in right hippocampal volume is a statistically significant predictor of poorer treatment response. Overall, the predictive information that is measurable with brain imaging techniques is both multimodal and regionally distributed as it contains functional as well as structural correlates which encompass several brain regions within a frontostriatal-limbic network. To develop clinically relevant, prognostic markers will require high predictive accuracy at the level of the individual. Predicting clinical response will help to stratify patients and to identify at an early stage those patients who may require more intensive or combined therapies. We propose that structural and functional neuroimaging show significant potential for the development of prognostic markers of clinical response in the treatment of depression.

The interplay between cognition, functional and dual-task gait in persons with a vestibular disorder versus healthy controls.

Close links exist between vestibular function and cognition. Dual-task (DT) tests may have ecological validity to assess the impact of daily life cognitive-motor demands in people with vestibular dysfunction (PwVD), functional gait and falls risk. The present paper aimed at building predictive models for functional gait under DT conditions, while clarifying the impact of vestibular dysfunction, individual characteristics, varying task types and motor-cognitive demands. Case-controlled observational study with 39 PwVD and 62 healthy participants. The Functional Gait Assessment (FGA), with and without an additional motor, numeracy, or literacy task, was completed. Multiple linear regression was used to fit models to predict FGA under single and DT performance. Dual task cost (DTC, %) was calculated to assess DT interference on FGA performance using the equation: 100*(single task score-dual task score)/single-task score. Following Bonferroni corrections for multiple comparisons (corrected alpha level of 0.003), PwVD had poorer performance than controls for all FGA conditions (p < 0.001), motor (- 3.94%; p = 0.002) and numeracy (- 22.77%; p = 0.001) DTCs and spatial working memory (p = 0.002). The literacy DTC was marginally significant (- 19.39% p = 0.005). FGA single and DT motor, numeracy, and literacy models explained 76%, 76%, 66% and 67% of the variance respectively for PwVD. Sustained attention, visual memory and sex contributed to all models; short-term visual recognition memory, balance confidence, and migraine contributed to some models. Cognitive performance is impaired in PwVD. Motor, numeracy and literacy tasks impair functional gait performance. Cognitive assessment and FGA with a numeracy or literacy cognitive component should be included within assessment protocols and considered in the provision of targeted interventions for PwVD.

How do care home staff use non-pharmacological strategies to manage sleep disturbances in residents with dementia: The SIESTA qualitative study.

BACKGROUND: Sleep disturbances affect 38% of care home residents living with dementia. They are often treated with medication, but non-pharmacological interventions may be safer and effective yet more difficult to implement. In the SIESTA study (Sleep problems In dEmentia: interviews with care home STAff) we explored care home staffs' experience of managing sleep disturbances in their residents living with dementia. METHODS: We conducted one-to-one semi-structured interviews in four UK care homes, and purposively recruited a maximum variation sample of 18 nurses and care assistants, who were each interviewed once. We used a topic guide and audio-recorded the interviews. Two researchers independently analysed themes from transcribed interviews. RESULTS: Staff used a range of techniques that often worked in improving or preventing residents' sleep disturbance. During the daytime, staff encouraged residents to eat well, and be physically active and stimulated to limit daytime sleep. In the evening, staff settled residents into dark, quiet, comfortable bedrooms often after a snack. When residents woke at night, they gave them caffeinated tea or food, considered possible pain and discomfort, and reassured residents they were safe. If residents remained unsettled, staff would engage them in activities. They used telecare to monitor night-time risk. Staff found minimising daytime napping difficult, described insufficient staffing at night to attend to reorient and guide awake residents and said residents frequently did not know it was night-time. CONCLUSIONS: Some common techniques, such as caffeinated drinks, may be counterproductive. Future non-pharmacological interventions should consider practical difficulties staff face in managing sleep disturbances, including struggling to limit daytime napping, identifying residents' night-time needs, day-night disorientation, and insufficient night-time staffing.

Care home residents with dementia: Prevalence, incidence, and associations with sleep disturbance in an English cohort study.

INTRODUCTION: People living with dementia in care homes often have sleep disturbances, but little is known about incidence and importance. METHODS: We interviewed 1483 participants in 97 care homes and report prevalence, 1-year incidence, and baseline associations of clinically significant sleep disturbance in people with dementia. RESULTS: Baseline prevalence of clinically significant sleep disturbance was 13.7% (200/1460); 31.3% (457/1462) had them at least once over 16 months. One-year incidence was 25.2%. At baseline, residents with sleep disturbance had lower quality of life (mean difference -4.84; 95% confidence interval [CI] -6.53 to -3.16) and were more frequently prescribed sleep medications (odds ratio 1.75; CI 1.17 to 2.61) than other residents. DISCUSSION: Approximately one-third of care home residents with dementia have or develop sleep disturbances over 1 year. These are associated with lower quality of life and prescription of sedatives, which may have negative outcomes; therefore, it is important to develop effective treatments.

Machine learning classification with confidence: application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression.

There is rapidly accumulating evidence that the application of machine learning classification to neuroimaging measurements may be valuable for the development of diagnostic and prognostic prediction tools in psychiatry. However, current methods do not produce a measure of the reliability of the predictions. Knowing the risk of the error associated with a given prediction is essential for the development of neuroimaging-based clinical tools. We propose a general probabilistic classification method to produce measures of confidence for magnetic resonance imaging (MRI) data. We describe the application of transductive conformal predictor (TCP) to MRI images. TCP generates the most likely prediction and a valid measure of confidence, as well as the set of all possible predictions for a given confidence level. We present the theoretical motivation for TCP, and we have applied TCP to structural and functional MRI data in patients and healthy controls to investigate diagnostic and prognostic prediction in depression. We verify that TCP predictions are as accurate as those obtained with more standard machine learning methods, such as support vector machine, while providing the additional benefit of a valid measure of confidence for each prediction.

Automated hippocampal shape analysis predicts the onset of dementia in mild cognitive impairment.

The hippocampus is involved at the onset of the neuropathological pathways leading to Alzheimer's disease (AD). Individuals with mild cognitive impairment (MCI) are at increased risk of AD. Hippocampal volume has been shown to predict which MCI subjects will convert to AD. Our aim in the present study was to produce a fully automated prognostic procedure, scalable to high throughput clinical and research applications, for the prediction of MCI conversion to AD using 3D hippocampal morphology. We used an automated analysis for the extraction and mapping of the hippocampus from structural magnetic resonance scans to extract 3D hippocampal shape morphology, and we then applied machine learning classification to predict conversion from MCI to AD. We investigated the accuracy of prediction in 103 MCI subjects (mean age 74.1 years) from the longitudinal AddNeuroMed study. Our model correctly predicted MCI conversion to dementia within a year at an accuracy of 80% (sensitivity 77%, specificity 80%), a performance which is competitive with previous predictive models dependent on manual measurements. Categorization of MCI subjects based on hippocampal morphology revealed more rapid cognitive deterioration in MMSE scores (p<0.01) and CERAD verbal memory (p<0.01) in those subjects who were predicted to develop dementia relative to those predicted to remain stable. The pattern of atrophy associated with increased risk of conversion demonstrated initial degeneration in the anterior part of the cornus ammonis 1 (CA1) hippocampal subregion. We conclude that automated shape analysis generates sensitive measurements of early neurodegeneration which predates the onset of dementia and thus provides a prognostic biomarker for conversion of MCI to AD.

Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder.

BACKGROUND: Impairments in executive function and language processing are characteristic of both schizophrenia and bipolar disorder. Their functional neuroanatomy demonstrate features that are shared as well as specific to each disorder. Determining the distinct pattern of neural responses in schizophrenia and bipolar disorder may provide biomarkers for their diagnoses. METHODS: 104 participants underwent functional magnetic resonance imaging (fMRI) scans while performing a phonological verbal fluency task. Subjects were 32 patients with schizophrenia in remission, 32 patients with bipolar disorder in an euthymic state, and 40 healthy volunteers. Neural responses to verbal fluency were examined in each group, and the diagnostic potential of the pattern of the neural responses was assessed with machine learning analysis. RESULTS: During the verbal fluency task, both patient groups showed increased activation in the anterior cingulate, left dorsolateral prefrontal cortex and right putamen as compared to healthy controls, as well as reduced deactivation of precuneus and posterior cingulate. The magnitude of activation was greatest in patients with schizophrenia, followed by patients with bipolar disorder and then healthy individuals. Additional recruitment in the right inferior frontal and right dorsolateral prefrontal cortices was observed in schizophrenia relative to both bipolar disorder and healthy subjects. The pattern of neural responses correctly identified individual patients with schizophrenia with an accuracy of 92%, and those with bipolar disorder with an accuracy of 79% in which mis-classification was typically of bipolar subjects as healthy controls. CONCLUSIONS: In summary, both schizophrenia and bipolar disorder are associated with altered function in prefrontal, striatal and default mode networks, but the magnitude of this dysfunction is particularly marked in schizophrenia. The pattern of response to verbal fluency is highly diagnostic for schizophrenia and distinct from bipolar disorder. Pattern classification of functional MRI measurements of language processing is a potential diagnostic marker of schizophrenia.

The Screening Accuracy of a Visually Based Montreal Cognitive Assessment Tool for Older Adult Hearing Aid Users.

OBJECTIVES: This research aims to validate a modified visually based Montreal Cognitive Assessment for hearing-aid users (MoCA-HA). This population should be the target of cognitive screening due to high risk of developing dementia. DESIGN: Case-control study. SETTING: The participants were recruited from referral hearing-aid center and memory clinic in central London, United Kingdom. PARTICIPANT: 75 hearing-aid users were recruited. Of these, thirty were cognitively intact controls with hearing impairment (NC-HI); thirty had mild cognitive impairment with hearing impairment (MCI-HI); fifteen had dementia with hearing impairment (D-HI). MEASUREMENTS: The baseline characteristics and analysis of the MoCA-HA for the NC-HI were recorded. The MoCA-HA performance of the MCI-HI cohort and D-HI cohort were also studied. RESULTS: The cutpoint of <26 yields 93.3% sensitivity with 80% specificity in distinguishing MCI-HI from NC-HI. The specificity increased to 95.6% in screening for all cognitive impairment (MCI-HI and D-HI) from NC-HI. CONCLUSION: The MoCA-HA has been validated with a cutpoint which is comparable to the traditional MoCA. This tool may help clinicians to early identify older adult hearing-aid users for appropriate cognitive evaluation.

Neuropsychological deficits in Posterior Cortical Atrophy and typical Alzheimer's disease: A meta-analytic review.

AIMS: To identify cognitive tests that best differentiate between Posterior Cortical Atrophy (PCA) and typical Alzheimer's Disease (tAD), as well as PCA and healthy control (HC) participants. METHOD: Medline, PsycInfo and Web of Science were systematically searched using terms related to PCA, tAD, and cognitive testing. Seventeen studies were identified, including 441 PCA, 391 tAD, and 284 HC participants. Standardised effect sizes of mean scores were calculated to measure performance differences on cognitive tests for PCA versus tAD and PCA versus HC groups. Meta-analyses used a random effects model. RESULTS: The most discriminating cognitive tests for PCA and tAD presentations were measures of visuospatial function and verbal memory. Large, significant effect sizes were produced for all measures of visuospatial function, most notably for Rey-Osterrieth Copy (Hedges' g = -2.79), VOSP Fragmented letters (Hedges' g = -1.73), VOSP Dot Counting (Hedges' g = -1.74), and VOSP Cube Analysis (Hedges' g = -1.98). For measures of verbal memory, the RAVLT delay and Digit Span Backwards produced significant medium effects (Hedges' g = .62 and -.56, respectively). CONCLUSION: Establishing a common framework for testing individuals with PCA has important implications for diagnosis and treatment, and forms a practical objective for future research. Findings from this meta-analysis suggest that measures of visuospatial function and verbal memory would form an important part of this framework.