A MIMIC Model Approach to Research in Geriatric Neuropsychology: The Case of Vascular Dementia

The goal of the current study is to demonstrate a new methodology that can be used in neuropsychological research concerning differential diagnosis research. The multiple indicators, multiple causes (MIMIC) model is a latent variable methodology which can examine group differences on individual tests while controlling group differences in global cognitive impairment. As a demonstration, neuropsychological data from 217 dementia patients were incorporated into a MIMIC model to examine the influence of cerebrovascular disease (CVD) upon (1) dimensions of global cognitive impairment and (2) upon individual tests after controlling for global impairment. The presence of CVD in dementia (i.e., vascular dementia [VaD]) was not significantly related to dimensions of global impairment. In addition, the presence of CVD within dementia did not significantly contribute to impairment on 9 out of 10 neuropsychological tests/subscales examined after controlling global cognitive impairment. These results are discussed in the context of current vascular dementia research, and are focused primarily upon the MIMIC model methodology and suggestions for its use in future research.     

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.     

The semantic category effect increases with worsening anomia in Alzheimer's type dementia

A large number of patients (n=72) with probable Alzheimer's type dementia (DAT) and mild cognitive impairment (MCI) carried out a picture naming task which comprised stimuli from biological and nonbiological categories. The results were stratified into five ranges of overall naming ability. Every group except those with scores within the range of elderly normal individuals demonstrated better nonbiological naming than biological naming, an effect which increased with worsening impairment. In general, patients diagnosed with other dementia (n=15) did not fit well within the pattern of the DAT/MCI participants, except those known to have a significant semantic impairment. A category effect favoring nonbiological items appears to be robust and produce a predictable pattern across progressive levels of impairment in AD.     

Health numeracy and cognitive decline in advanced age

ABSTRACT

The study aimed at investigating health numeracy in cognitively well performing healthy participants aged from 50 to 95 years as well as in participants with cognitive impairment, but no dementia (CIND). In cognitively well performing participants (n = 401), demographic variables and cognitive abilities (executive functions, reading comprehension, mental calculation, vocabulary) were associated with health numeracy. Older age, lower education, female gender as well as lower cognitive functions predicted low health numeracy. The effect of older age was partly mediated by executive functions and calculation abilities. Participants with CIND (n = 51) performed significantly lower than healthy controls in health numeracy. The findings suggest that cognitively well performing old individuals have difficulties in understanding health-related numerical information. The risk of misunderstanding health-related numerical information is increased in persons with CIND. As these population groups are frequently involved in health care decisions, particular attention has to be paid to providing numerical information in comprehensible form.     

Mood congruent memory in dysphoria: the roles of state affect and cognitive style

Biases in incidental memory for self-referent adjectives and intentional memory were compared across nondysphoric (ND; n=48), experimentally induced dysphoric (EXP; n=49), and naturally dysphoric (NAT; n=48) individuals. Negative biases, "evenhandedness", and positive biases were demonstrated among NAT, EXP and ND participants, respectively, in terms of incidental memory. Correlation analyses suggested that the effects of cognitive style (self-esteem, dysfunctional attitudes, and attributional style) are limited to negative stimuli. Memory for incidental positive stimuli was only predicted by state affect. Groups did not differ in performance on an intentional memory task. Implications for network and schema models of depression are explored.     

Modeling and estimating recall processing capacity: Sensitivity and diagnostic utility in application to mild cognitive impairment

We investigate the potential for using latency-based measures of retrieval processing capacity to assess changes in performance specific to individuals with mild cognitive impairment (MCI), a reliable precursor state to Alzheimer’s Disease. Use of these capacity measures is motivated in part by exploration of the effects of atrophy on a computational model of a basic hippocampal circuit. We use this model to suggest that capacity may be a more sensitive indicator of the underlying atrophy than speed of processing, and test this hypothesis by adapting a standard behavioral measure of memory (the free and cued selective reminding test, FCSRT) to allow for the collection of cued recall latencies. Participants were drawn from five groups: college-aged, middle-aged, healthy elderly, those with a diagnosis of MCI, and a sample of MCI control participants. The measure of capacity is shown to offer increased classificatory sensitivity relative to the standard behavioral measures, and is also shown to be the behavioral measure that correlated most strongly with hippocampal volume.     

Cognition, daily living, and health-related quality of life in 85-year-olds in Sweden

This study investigates how cognition influences activities of daily living and health-related quality of life in 85-year-olds in Sweden (n = 373). Data collection included a postal questionnaire comprising demographics and health-related quality of life measured by the EQ-5D. The ability to perform personal activities of daily living (PADL) was assessed during a home visit that included administering the Mini Mental State Examination (MMSE). Cognitive impairment was shown in 108 individuals (29%). The majority were independent with respect to PADL. A larger number of participants with cognitive impairment reported that they needed assistance in instrumental activities of daily living (IADL) compared to the group without cognitive impairment. Impaired cognition was significantly related to problems with IADL. Significant but low correlations were found between cognition and health-related quality of life - higher ratings on perceived quality of life correlated with higher results on the MMSE.     

Neuropsychological Measures that Predict Progression from Mild Cognitive Impairment to Alzheimer's type dementia in Older Adults: a Systematic Review and Meta-Analysis

This study aimed to determine the extent to which cognitive measures can predict progression from mild cognitive impairment (MCI) to Alzheimer’s type dementia (AD), assess the predictive accuracy of different cognitive domain categories, and determine whether accuracy varies as a function of age and length of follow-up. We systematically reviewed and meta-analyzed data from longitudinal studies reporting sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will develop AD. We searched articles in Medline, Cochrane, EMBASE, PsycINFO, and the Web of Science. Methodological quality was assessed using the STARDem and QUADAS standards. Twenty-eight studies met the eligibility criteria (2365 participants) and reported predictive values from 61 neuropsychological tests with a 31-month mean follow-up. Values were pooled to provide combined accuracy for 14 cognitive domains. Many domains showed very good predictive accuracy with high sensitivity and specificity values (≥ 0.7). Verbal memory measures and many language tests yielded very high predictive accuracy. Other domains (e.g., executive functions, visual memory) showed better specificity than sensitivity. Predictive accuracy was highest when combining memory measures with a small set of other domains or when relying on broad cognitive batteries. Cognitive tests are excellent at predicting MCI individuals who will progress to dementia and should be a critical component of any toolkit intended to identify AD at the pre-dementia stage. Some tasks are remarkable as early indicators, whereas others might be used to suggest imminent progression.     

Do subjective measures of attention and memory predict actual performance? Metacognition in older couples

Older individuals who recognize their cognitive difficulties are more likely to adjust their everyday life to their actual cognitive functioning, particularly when they are able to estimate their abilities accurately. We assessed self- and spouse-ratings of memory and attention difficulties in everyday life of healthy, older individuals and compared them with the respective test performance. Eighty-four older individuals (women's age, M = 67.4 years, SD = 5.2; men's age, M = 68.5 years, SD = 4.9) completed both the self and the spouse versions of the Attention Deficit Questionnaire and the Everyday Memory Questionnaire and completed two neuropsychological tests. Using the residual score approach, subjective metacognitive measures of memory and attention were created and compared with actual test performance. Significant associations between subjective and objective scores were found only for men and only for episodic memory measures. Men who underreported memory difficulties performed more poorly; men who overreported memory difficulties performed better. Men's recognition performance was best predicted by subjective measures (R2 = .25), followed by delayed recall (R2 = .14) and forgetting rate (R2 = .13). The results indicate gender-specific differences in metacognitive accuracy and predictive validity of subjective ratings.     

Atrophy of the parietal lobe in preclinical dementia

Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults (38 cognitively stable and 37 individuals with cognitive decline after 3 years). Dementia screening 6 years after scanning resulted in nine AD cases from the cognitively stable (n=3) and cognitive decline group (n=6), who were assigned to a third group, the preclinical AD group. When regional differences in cortical volume in the parietal lobe areas were compared between groups, significant differences were found between either the cognitive decline or stable group on the one hand and preclinical AD individuals on the other hand in the inferior parietal lobule. Group membership was best predicted by the grey matter volume of the inferior parietal lobule, compared to the other parietal lobe areas. The parietal lobe was characterised by a differential atrophy pattern based on cognitive status, which is in agreement with the 'last-developed-first-atrophied' principle. Future studies should investigate the surplus value of the inferior parietal lobe as a potential marker for the diagnosis of AD compared to other brain regions, such as the medial temporal lobe and the prefrontal lobe.     

Differential Memory Test Sensitivity for Diagnosing Amnestic Mild Cognitive Impairment and Predicting Conversion to Alzheimer's Disease

ABSTRACT

Episodic memory is the first and most severely affected cognitive domain in Alzheimer's disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia.     

Early Cognitive Decline and Its Impact On Spouse’s Loneliness

Loneliness is common in dementia caregivers as cognitive impairment (CI) alters marital and social relationships. Unexplored is how an individual’s loneliness is affected at earlier, more ambiguous, periods of their spouse’s CI. Using the Health and Retirement Study, our study participants included 2,206 coupled individuals with normal cognitive function at the 2006/8 baseline. Loneliness outcomes at baseline, 4-year, and 8-year follow-up are assessed by the status of transition to cognitive impairment no dementia (TCIND) (2010/12 & 2014/16) using linear mixed models. Individual’s loneliness was stable when their spouse’s cognition remained normal, but increased with the spouse’s TCIND. The increase in loneliness did not vary by gender. Loneliness, a key risk factor for reduced life quality and increased depression, increases even at early stages of a partner’s CIND. This work suggests the potential impact of early intervention and social support for partners of individuals with CIND.     

The Effect of Non-Stroke Cardiovascular Disease States on Risk for Cognitive Decline and Dementia: A Systematic and Meta-Analytic Review

Cardiovascular disease is associated with increased risk for cognitive decline and dementia, but it is unclear whether this risk varies across disease states or occurs in the absence of symptomatic stroke. To examine the evidence of increased risk for cognitive decline and dementia following non-stroke cardiovascular disease we conducted two independent meta-analyses in accordance with PRISMA guidelines. The first review examined cardiovascular diagnoses (atrial fibrillation, congestive heart failure, periphery artery disease and myocardial infarction) while the second review assessed the impact of atherosclerotic burden (as indicated by degree of stenosis, calcification score, plaque morphology or number of plaques). Studies eligible for review longitudinally assessed risk for clinically significant cognitive decline and/or dementia and excluded stroke and cognitive impairment at baseline. Summary statistics were computed via the inverse variance weighted method, utilising Cox Proportional Hazards data (Hazard Ratios, HR). Both atrial fibrillation (n = 5, HR = 1.26, 95% CI [1.12, 1.43]) and severe atherosclerosis (n = 4, HR = 1.59, 95% CI [1.12, 2.26]) emerged as significant risk factors for cognitive decline and/or dementia. A small set of studies reviewed, insufficient for meta-analysis, examining congestive heart failure, peripheral artery disease and myocardial infarction suggested that these conditions may also be associated with an increased risk of cognitive decline/dementia. In the absence of stroke, patients with atrial fibrillation or generalised atherosclerosis are at heightened risk for cognitive deterioration. Nonetheless, this paper highlights the need for methodologically rigorous and prospective investigation of the relationship between CVD and dementia.     

Automatic processing in spider phobia: implicit fear associations over the course of treatment

This study evaluates the cognitive model of anxiety by investigating treatment-related changes in automatic associations to evaluate schematic processing. Spider-phobic participants (n = 31) and healthy controls (n = 30) completed fear-based Implicit Association Tests (IATs), which are reaction-time measures that tap implicit associations without requiring conscious introspection. The specific tasks involved classifying pictures of snakes and spiders along with semantic categorizations (good vs.bad, afraid vs. unafraid, danger vs. safety, and disgusting vs. appealing). Phobic individuals were assessed before and after group-based exposure treatment and 2 months later, controls were assessed at matched time points. Results supported clinical applications for implicit fear associations, including prediction of phobic avoidance, and treatment sensitivity of the fear- and disgust-specific automatic associations.     

Awareness of memory task impairment versus everyday memory difficulties in dementia

The study investigated different types of awareness of memory dysfunction in dementia, specifically judgements concerning memory task performance or appraisal of everyday memory functioning and also exploring the neuropsychological correlates of such awareness. This was investigated in 76 people with dementia, comprising 46 patients with Alzheimer's disease (AD) and 30 patients with vascular dementia (VaD). The Memory Awareness Rating Scale (Clare et al., 2002, Neuropsychol Rehabil, 12, 341–362) was used, which includes an Objective‐Judgement Discrepancy (OJD) technique involving comparison of subjective evaluation of performance on specific memory tasks with actual performance, and a Subjective Rating Discrepancy (SRD) technique, which compares self versus informant judgement of everyday memory function. The AD and VaD groups showed lower awareness than a normal control group for both types of measures, the AD group showing less awareness than the VaD group on the OJD measure. Regression analyses supported associations for both groups between memory impairment and the OJD measure and between naming impairment and the SRD measure. The findings are discussed in terms of neurocognitive theories accounting for loss of awareness in dementia.     

Depression and distress predict time to cardiovascular disease in dementia caregivers.

OBJECTIVE: This study assessed the impact of depressive symptoms and distress from patient problem behaviors on time to developing a diagnosis of cardiovascular disease (CVD) in a sample of 643 dementia family caregivers. DESIGN: A longitudinal, prospective design was used. Over an 18-month period, caregivers free from a CVD diagnosis at baseline were assessed at 6, 12, and 18-month follow-ups for the onset of CVD. MAIN OUTCOME MEASURES: Days to the onset of CVD was the primary outcome. RESULTS: Over the length of the study, 32 participants (5%) reported a diagnosis of CVD. After adjusting for sociodemographic and health factors (e.g., high blood pressure, age, smoking history), greater depressive symptoms (p = .040) and distress from patient problem behaviors (p = .034) were significant predictors of time to CVD diagnosis. CONCLUSION: This study suggests that increased depressive symptoms and reaction to patient problem behaviors (i.e., distress) may increase caregivers' risk for experiencing negative health outcomes, specifically CVD.     

Hope and cardiovascular health-promoting behaviour: Education alone is not enough

We investigated hope’s ability to predict cardiovascular disease (CVD) knowledge and health-promoting behaviours. Snyder defined hope as the combination of goal-directed planning and motivation, and theorised that high-hope people seek knowledge relevant to goal pursuits. We surveyed 391 Latino and Asian participants undergoing CVD risk screening, nearly all immigrants to the USA. This was a particularly important sample because, in general, these populations are considered underserved and under-researched. Pre-screening hope levels were measured. After screening and education, participants rated perceived importance of behaviour change. Behaviour change (salt/fat intake, exercise, CVD information-seeking and visiting a physician) and CVD knowledge were assessed one month later by telephone. Unexpectedly, hope did not predict knowledge. However, hope predicted self-reported behaviour change, though results differed by ethnicity. Among Asian individuals, hope?×?knowledge predicted reduced salt/fat, CVD information-seeking and physician visits. Among Latino individuals, hope?×?perceived importance of diet change predicted reduced salt/fat and hope?×?perceived importance of exercise change predicted increased exercise.     

Psychometric properties of an insomnia-specific measure of worry: the Anxiety and Preoccupation about Sleep Questionnaire

The aim of this study was to examine the psychometric properties of the Anxiety and Preoccupation about Sleep Questionnaire (APSQ), with a focus on factorial validity and internal consistency as well as discriminative, convergent, and association with sleep parameters and daytime impairment. Among a randomly selected sample from the general population (N = 5,000), 2,333 participants completed a survey on nighttime symptoms, daytime symptoms, health outcomes, and psychological processes. The study sample consisted of 1800 participants who did not fulfill criteria for another sleep disorder than insomnia. A two-factor solution, accounting for 70.7% of the variance, was extracted from the 10 APSQ items. One six-item factor determined worries about the consequences of poor sleep (α = .91); the second factor, with four items, assessed worries about the uncontrollability of sleep (α = .86). The two factors were significantly intercorrelated (ρ = .65) and significantly associated with the total APSQ (ρs = .97 and .76, respectively). The APSQ and the two subscales showed discriminant validity between three sleep status groups (normal sleep, poor sleep, and insomnia disorder; R(2) = .33-.41). The APSQ and the subscales demonstrated convergent validity with measures on cognitive arousal, sleep-related beliefs, anxiety, and depression. They also were significantly correlated with sleep parameters and daytime impairment. The findings suggest that the APSQ is a psychometrically sound instrument for assessing worry in insomnia.     

Reduced electrodermal activity in psychopathy-prone adolescents

This study tests the hypothesis that psychopathy-prone adolescents show reduced anticipatory skin conductance responding. Electrodermal activity was recorded while participants anticipated and responded to a 105 dB signaled or unsignaled white-noise burst. Using an extreme groups design, the authors used Child Psychopathy Scale (D. R. Lynam, 1997) scores from a community sample of 335 male adolescents (age 16) to form control (n = 65) and psychopathy-prone (n = 65) groups. Significantly more psychopathy-prone participants were nonresponders in the signaled anticipatory (p = .014), signaled responsivity (p = .037), and unsignaled responsivity (p = .003) conditions compared with controls. Anticipatory hyporesponsivity of psychopathy-prone adolescents similar to the electrodermal hyporesponsivity found in psychopathic adults suggests that this autonomic impairment is present by adolescence and may predispose individuals to adult psychopathy.     

Neuropsychology,genetic liability,and psychotic symptoms in those at high risk of schizophrenia

Neuropsychological assessments were compared among individuals at enhanced genetic risk of schizophrenia (n = 157) and controls (n = 34). The relationship between cognitive impairments and the presence of psychotic symptoms and measures of genetic risk was explored in the high-risk subjects. Neuropsychological differences were identified in many areas of function and were not accounted for by the presence of psychotic symptoms. Genetic liability was not associated with neuropsychological performance or with psychotic symptoms, but exploratory analysis showed some tests were associated with both liability measures. These results suggest that what is inherited is not the disorder itself but a state of vulnerability manifested by neuropsychological impairment, occurring in many more individuals than are predicted to develop the disorder.