Longitudinal post-shunt outcomes in idiopathic normal pressure hydrocephalus with and without comorbid Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity. METHODS: Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24-60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively. RESULTS: There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence. CONCLUSION: iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.

Boston cognitive assessment (BOCA) - a comprehensive self-administered smartphone- and computer-based at-home test for longitudinal tracking of cognitive performance.

Longitudinal cognitive testing is essential for developing novel preventive interventions for dementia and Alzheimer's disease; however, the few available tools have significant practice effect and depend on an external evaluator. We developed a self-administered 10-min at-home test intended for longitudinal cognitive monitoring, Boston Cognitive Assessment or BOCA. The goal of this project was to validate BOCA. BOCA uses randomly selected non-repeating tasks to minimize practice effects. BOCA evaluates eight cognitive domains: 1) Memory/Immediate Recall, 2) Combinatorial Language Comprehension/Prefrontal Synthesis, 3) Visuospatial Reasoning/Mental rotation, 4) Executive function/Clock Test, 5) Attention, 6) Mental math, 7) Orientation, and 8) Memory/Delayed Recall. BOCA was administered to patients with cognitive impairment (n = 50) and age- and education-matched controls (n = 50). Test scores were significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach's alpha was 0.87 implying good internal consistency. BOCA demonstrated strong correlation with Montreal Cognitive Assessment (MoCA) (R = 0.90, p < 0.001). The study revealed strong (R = 0.94, p < 0.001) test-retest reliability of the total BOCA score one week after participants' initial administration. The practice effect tested by daily BOCA administration over 10 days was insignificant (ß = 0.03, p = 0.68). The effect of the screen size tested by BOCA administration on a large computer screen and re-administration of the BOCA to the same participant on a smartphone was insignificant (ß = 0.82, p = 0.17; positive ß indicates greater score on a smartphone). BOCA has the potential to reduce the cost and improve the quality of longitudinal cognitive tracking essential for testing novel interventions designed to reduce or reverse cognitive aging. BOCA is available online gratis at www.bocatest.org .

Novel linguistic evaluation of prefrontal synthesis (LEPS) test measures prefrontal synthesis acquisition in neurotypical children and predicts high-functioning versus low-functioning class assignment in individuals with autism.

In order to grasp the difference between "the cat on the mat" and "the mat on the cat," understanding the words and the grammar is not enough. Rather it is essential to visualize the cat and the mat together to appreciate their relations. This type of imagination, which involves juxtaposition of mental objects is conducted by the prefrontal cortex and is therefore called Prefrontal Synthesis (PFS). PFS acquisition has a strong experience-dependent critical period putting children with language delay in danger of never acquiring PFS and, consequently, not mastering complex language comprehension. In typical children, the timeline of PFS acquisition correlates with vocabulary expansion. Conversely, atypically developing children may learn many words but never acquire PFS. In these individuals, intelligence tests based on vocabulary assessment may miss the profound deficit in PFS. Accordingly, we developed a test specific for PFS - Linguistic Evaluation of Prefrontal Synthesis or LEPS - and administered it to 50 neurotypical children, age 4.1 ± 1.3 years and to 23 individuals with impairments, age 16.4 ± 3.0 years. All neurotypical children older than 4 years received the LEPS score 7/10 or greater indicating good PFS ability. Among individuals with impairments only 39% received the LEPS score 7/10 or greater. LEPS was 90% correct in predicting high-functioning vs. low-functioning class assignment in individuals with impairments.

The Boston cognitive assessment: Psychometric foundations of a self-administered measure of global cognition.

Objective: The Boston Cognitive Assessment (BoCA) is a novel, computerized, self-administered assessment of global cognition. This work sought to establish the validity and reliability of the BoCA. Method: Two studies were conducted. The first study used a sample of 43 outpatients from a clinic in eastern Massachusetts to evaluate the content validity and internal consistency of the BoCA. The second study used a sample of 38 patients seen at an outpatient specialty neurological clinic to evaluate the BoCA's test-retest reliability after one week. Results: In the first study, participants without cognitive diagnoses scored significantly higher on both the BoCA and the Telephone Interview for Cognitive Status (TICS) compared to those with mild Neurocognitive Disorders. Correlational analyses revealed moderate correlations between several of the BoCA tasks and measures of related abilities. Exploratory factor analysis of the BoCA tasks revealed one robust factor accounting for a plurality (i.e., 42%) of variance in participant scores. The BoCA demonstrated good internal consistency (α = 0.79) and strong correlations (r = 0.80, p < 0.01) with the TICS. The second study revealed strong (r = 0.89, p < 0.001) test-retest reliability of the total BoCA score one week after participants' initial administration. Conclusions: This work provides evidence of the BoCA's psychometric properties as a self-administered screener of global cognition, and supports its implementation in clinical practice and future studies. Clinical implications, future directions, and limitations are discussed.

Frontal Behavior Syndromes in Idiopathic Normal Pressure Hydrocephalus as a Function of Alzheimer's Disease Biomarker Status.

OBJECTIVES: Cognitive impairment and apathy are well-documented features of idiopathic normal pressure hydrocephalus (iNPH). However, research examining other neuropsychiatric manifestations of iNPH is scant, and it is unknown whether the neuropsychiatric presentation differs for iNPH patients with comorbid Alzheimer's disease (AD) versus iNPH without AD. This study aims to advance our understanding of neuropsychiatric syndromes associated with iNPH. METHODS: Fifty patients from Butler Hospital's Normal Pressure Hydrocephalus Clinic met inclusion criteria. Caregiver ratings on the Frontal Systems Behavior Scale (FrSBe) were examined to appraise changes in apathy, executive dysfunction, and disinhibition. Patients also completed cognitive tests of global cognition, psychomotor speed, and executive functioning. AD biomarker status was determined by either amyloid-beta (Aß) positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) total tau to Aß-42 ratio. RESULTS: Results revealed clinically significant elevations on the FrSBe's apathy and executive dysfunction scales and modest correlations among these scales and cognitive measures. Of the 44 patients with available neuroimaging or CSF draw data, 14 presented with comorbid AD. Relative to the iNPH-only group, the iNPH + AD group showed a larger increase from pre-illness to current informant ratings on the executive dysfunction scale, but not the apathy or disinhibition scales. CONCLUSIONS: These results replicate and extend prior research by identifying apathy and executive dysfunction as prominent neuropsychiatric symptoms of iNPH and suggest comorbid AD exacerbates dysexecutive behaviors. Future research is warranted to examine the effects of comorbid AD pathology in response to shunt surgery for iNPH, neuropsychiatric symptom changes, and resultant caregiver burden.

Comparing patient and informant ratings of depressive symptoms in various stages of Alzheimer's disease.

OBJECTIVE: Using a multimethod approach, this study assessed the relationship between patient and informant ratings of depression in Alzheimer's disease (AD) in a manner that better represents the progressive course of AD, and allows for elucidation of specific cognitive domains that may explain changes in respondent agreement. METHOD: Case data (N = 16,297) were provided by the National Alzheimer's Coordinating Center (NACC). A series of contingency analyses were performed to assess the relationship between patient and informant agreement across levels of impairment in individuals with AD. Patients and informants were placed into groups (i.e., not impaired, mild impairment, moderate impairment, severe impairment) based on patients' performance on multiple indicators of global cognitive functioning, as well as measures of attention, working memory, processing speed, executive functioning, language, and episodic learning and memory. RESULTS: Across measures, greater impairment was significantly (p < .001) associated with decreases in patient-informant congruence and increases in rates of patients denying depression when informants endorsed observing features of the same. These inconsistencies were most pronounced in the mildest stages of impairment. For a subset of the sample, rates of patients reporting depressive symptoms when informants denied observing the same also increased alongside worsening impairment. Incremental impairment in episodic learning (χ² = 805.25) and memory (χ² = 856.94) performance were most closely associated with decreases in respondent agreement. Patient-informant relationship type did not appear to mediate the response patterns observed. CONCLUSIONS: Mild impairment in AD patients, particularly in episodic learning and memory functioning, is significantly associated with decreases in patient-informant agreement regarding the presence of depressive symptoms. These results suggest that even at the earliest stages of AD informant reports should be used to corroborate patients' reporting. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Neuropsychological profile associated with Moyamoya disease: A case report.

BACKGROUND: Moyamoya disease (MMD) is a rare cardiovascular condition characterized by stenosis and gradual occlusion of the internal carotid arteries near the Circle of Willis. Current research on the disease has primarily been restricted to its medical implications, without adequate appreciation for its neurocognitive and/or neuropsychiatric implications. OBJECTIVES: The current study presents the neurocognitive profile of a 31-year-old woman diagnosed with MMD, further complicated by cerebral vascular accidents (CVAs) and history of bilateral craniotomy aimed at providing maximal revascularization. METHODS: Although speech and motor disturbances experienced by Ms. Doe around the time of her craniotomy and CVA were resolved at the time of current evaluation, she reported experiencing continued difficulties in processing speed, concentration, memory, word-retrieval, and planning. The patient underwent comprehensive neuropsychological evaluation assessing multiple cognitive domains. RESULTS: Neurocognitive evaluation revealed the presence of a lateralized profile as well as impairments in simple auditory attention, processing speed, working memory, verbal learning, verbal fluency, and speeded fine-motor dexterity. CONCLUSIONS: MMD significantly impacts cognition and daily functioning in affected individuals. This is often further exacerbated by additional CVAs requiring surgical intervention. While there is a clear growth of research on MMD, limited information is available on the neurocognitive and neuropsychiatric outcomes of the disease process. Neuropsychological data from the current case study is closely examined to provide a unique example of the lateralized neuropsychological profile and deficit pattern in a historically high functioning individual diagnosed with MMD following a stroke.

Neuropsychological impairment in Hashimoto's encephalopathy: A case report and literature review.

Hashimoto's encephalopathy (HE) is a rare neurological syndrome characterized by the presence of positive serum antithyroid antibodies, altered mental status, and clinical response to glucocorticoid therapy. Although HE has been documented in the literature from a medical standpoint, reports on the neuropsychological presentation of this syndrome are scarce. This article presents a literature review of cognitive deficits reported in HE cases. In addition, we describe the case of a 76-year-old Russian speaking woman diagnosed with HE in May 2012. MRIs from her disease course and treatment are presented. Posttreatment neuropsychological testing revealed intact attention and construction and impairment in working memory, processing speed, learning, executive functioning, language, and bilateral fine motor dexterity, all of which impacted her functional abilities. Her profile was inconsistent with the typical dementia process. This case demonstrates the utility of neuropsychological assessment for understanding cognitive and functional consequences of HE. The issue of differential diagnosis with dementia is also discussed.

Alzheimer's disease and diet: a systematic review.

Purpose/Aim: Approximately 44 million people worldwide have Alzheimer's disease (AD). Numerous claims have been made regarding the influence of diet on AD development. The aims of this systematic review were to summarize the evidence considering diet as a protective or risk factor for AD, identify methodological challenges and limitations, and provide future research directions. METHODS: Medline, PsycINFO and PsycARTICLES were searched for articles that examined the relationship between diet and AD. RESULTS: On the basis of the inclusion and exclusion criteria, 64 studies were included, generating a total of 141 dietary patterns or "models". All studies were published between 1997 and 2015, with a total of 132 491 participants. Twelve studies examined the relationship between a Mediterranean (MeDi) diet and AD development, 10 of which revealed a significant association. Findings were inconsistent with respect to sample size, AD diagnosis and food measures. Further, the majority of studies (81.3%) included samples with mean baseline ages that were at risk for AD based on age (>65 years), ranging from 52.0 to 85.4 years. The range of follow-up periods was 1.5-32.0 years. CONCLUSIONS: The mean age of the samples poses a limitation in determining the influence of diet on AD; given that AD has a long prodromal phase prior to the manifestation of symptoms and decline. Further studies are necessary to determine whether diet is a risk or protective factor for AD, foster translation of research into clinical practice and elucidate dietary recommendations. Despite the methodological limitations, the finding that 50 of the 64 reviewed studies revealed an association between diet and AD incidence offers promising implications for diet as a modifiable risk factor for AD.

Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. METHODS: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). RESULTS: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p ≤ .001) and SDT (p<.001). CONCLUSIONS: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools.

White matter maturation profiles through early childhood predict general cognitive ability.

Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.

Estimating the age of healthy infants from quantitative myelin water fraction maps.

The trajectory of the developing brain is characterized by a sequence of complex, nonlinear patterns that occur at systematic stages of maturation. Although significant prior neuroimaging research has shed light on these patterns, the challenge of accurately characterizing brain maturation, and identifying areas of accelerated or delayed development, remains. Altered brain development, particularly during the earliest stages of life, is believed to be associated with many neurological and neuropsychiatric disorders. In this work, we develop a framework to construct voxel-wise estimates of brain age based on magnetic resonance imaging measures sensitive to myelin content. 198 myelin water fraction (VF(M) ) maps were acquired from healthy male and female infants and toddlers, 3 to 48 months of age, and used to train a sigmoidal-based maturational model. The validity of the approach was then established by testing the model on 129 different VF(M) datasets. Results revealed the approach to have high accuracy, with a mean absolute percent error of 13% in males and 14% in females, and high predictive ability, with correlation coefficients between estimated and true ages of 0.945 in males and 0.94 in females. This work represents a new approach toward mapping brain maturity, and may provide a more faithful staging of brain maturation in infants beyond chronological or gestation-corrected age, allowing earlier identification of atypical regional brain development.

Characterizing longitudinal white matter development during early childhood.

Post-mortem studies have shown the maturation of the brain's myelinated white matter, crucial for efficient and coordinated brain communication, follows a nonlinear spatio-temporal pattern that corresponds with the onset and refinement of cognitive functions and behaviors. Unfortunately, investigation of myelination in vivo is challenging and, thus, little is known about the normative pattern of myelination, or its association with functional development. Using a novel quantitative magnetic resonance imaging technique sensitive to myelin we examined longitudinal white matter development in 108 typically developing children ranging in age from 2.5 months to 5.5 years. Using nonlinear mixed effects modeling, we provide the first in vivo longitudinal description of myelin water fraction development. Moreover, we show distinct male and female developmental patterns, and demonstrate significant relationships between myelin content and measures of cognitive function. These findings advance a new understanding of healthy brain development and provide a foundation from which to assess atypical development.

Mixed effects of deep brain stimulation on depressive symptomatology in Parkinson's disease: a review of randomized clinical trials.

Although ~50% of patients with Parkinson's disease (PD) experience depression, treatment for this important and debilitating comorbidity is relatively understudied. Deep brain stimulation (DBS) has been increasingly utilized for the management of tremors in progressive PD. Several preliminary studies have shown the potential benefit of DBS for non-motor PD symptoms such as depression. Here, we critically evaluate seven recent randomized clinical trials of the effectiveness of DBS in reducing depressive symptomatology among individuals with PD. Findings are mixed for the effectiveness of DBS as a treatment for depression in PD. Our review suggests that this is due, in large part, to the anatomical and methodological variation across the DBS studies. We provide a comprehensive discussion of these variations and highlight the need to conduct larger, more controlled studies aimed specifically at evaluating the treatment of depression in PD patients.

Neuropsychiatric symptoms in an inpatient Parkinson's disease sample.

Background. Neuropsychiatric symptoms are common in idiopathic Parkinson's disease (PD), and hospitalization for delirium, depression, psychosis, and anxiety is sometimes required. A minimal amount of data exists on these patients. Methods. Charts of all patients admitted to a psychiatric hospital between 2006 and 2009 with a diagnosis of PD were reviewed. Forty-three met entry criteria and were reviewed. Initial and discharge diagnoses, comorbid psychiatric diagnoses, length of stay, and living arrangements before and after hospitalization are described. Results. Consistent with previous research, this study showed evidence of comorbid psychiatric disorders within PD. Conclusions. The long-term goal of this area of study would be to reduce neuropsychiatric symptoms and improve quality of life in order to reduce inpatient hospital stays.

White matter development and early cognition in babies and toddlers.

The normal myelination of neuronal axons is essential to neurodevelopment, allowing fast inter-neuronal communication. The most dynamic period of myelination occurs in the first few years of life, in concert with a dramatic increase in cognitive abilities. How these processes relate, however, is still unclear. Here we aimed to use a data-driven technique to parcellate developing white matter into regions with consistent white matter growth trajectories and investigate how these regions related to cognitive development. In a large sample of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume fraction (VFM ) maps using quantitative multicomponent relaxometry. We used spatial independent component analysis (ICA) to blindly segment these quantitative VFM images into anatomically meaningful parcels with distinct developmental trajectories. We further investigated the relationship of these trajectories with standardized cognitive scores in the same children. The resulting components represented a mix of unilateral and bilateral white matter regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum, white matter underlying the inferior frontal gyrus) as well as structured noise (misregistration, image artifact). The trajectories of these regions were associated with individual differences in cognitive abilities. Specifically, components in white matter underlying frontal and temporal cortices showed significant relationships to expressive and receptive language abilities. Many of these relationships had a significant interaction with age, with VFM becoming more strongly associated with language skills with age. These data provide evidence for a changing coupling between developing myelin and cognitive development.

Breastfeeding and early white matter development: A cross-sectional study.

Does breastfeeding alter early brain development? The prevailing consensus from large epidemiological studies posits that early exclusive breastfeeding is associated with improved measures of IQ and cognitive functioning in later childhood and adolescence. Prior morphometric brain imaging studies support these findings, revealing increased white matter and sub-cortical gray matter volume, and parietal lobe cortical thickness, associated with IQ, in adolescents who were breastfed as infants compared to those who were exclusively formula-fed. Yet it remains unknown when these structural differences first manifest and when developmental differences that predict later performance improvements can be detected. In this study, we used quiet magnetic resonance imaging (MRI) scans to compare measures of white matter microstructure (mcDESPOT measures of myelin water fraction) in 133 healthy children from 10 months through 4 years of age, who were either exclusively breastfed a minimum of 3 months; exclusively formula-fed; or received a mixture of breast milk and formula. We also examined the relationship between breastfeeding duration and white matter microstructure. Breastfed children exhibited increased white matter development in later maturing frontal and association brain regions. Positive relationships between white matter microstructure and breastfeeding duration are also exhibited in several brain regions, that are anatomically consistent with observed improvements in cognitive and behavioral performance measures. While the mechanisms underlying these structural differences remains unclear, our findings provide new insight into the earliest developmental advantages associated with breastfeeding, and support the hypothesis that breast milk constituents promote healthy neural growth and white matter development.

The APOE ε4 allele is associated with increased frontally mediated neurobehavioral symptoms in amnestic MCI.

The apolipoprotein E ε4 allele is a risk factor for late-onset Alzheimer disease (AD), and the frontal lobes may be among the regions that manifest effects of ε4 even early in the disease. We predicted that among patients with amnestic mild cognitive impairment (aMCI) and AD, ε4 would be associated with increased neurobehavioral symptoms when assessed using a measure sensitive to frontal lobe integrity. We obtained cognitive data and caregiver ratings on the Frontal Systems Behavior Scale (FrSBe) for aMCI patients (N=29 ε4 carriers; N=29 noncarriers) and AD patients (N=47 carriers; N=42 noncarriers). In both diagnostic groups, ε4 carriers had lower scores on tests of memory but did not differ on cognitive screening measures or tests of executive functioning. There were no differences in retrospective caregiver ratings of preillness status on the FrSBe by ε4 status in either diagnostic group. However, in the aMCI group, ε4 carriers had elevated current FrSBe Executive Dysfunction scores in comparison with noncarriers. In the AD group, there were no differences in current FrSBe scores by genotype group. Results indicate that ε4-related behavior change occurs in the aMCI stage but may not be apparent by the AD stage.

Using mental imagery to improve memory in patients with Alzheimer disease: trouble generating or remembering the mind's eye?

This study was conducted to understand whether patients with mild Alzheimer disease (AD) could use general or self-referential mental imagery to improve their recognition of visually presented words. Experiment 1 showed that, unlike healthy controls, patients generally did not benefit from either type of imagery. To help determine whether the patients' inability to benefit from mental imagery at encoding was due to poor memory or due to an impairment in mental imagery, participants performed 4 imagery tasks with varying imagery and cognitive demands. Experiment 2 showed that patients successfully performed basic visual imagery, but degraded semantic memory, coupled with visuospatial and executive functioning deficits, impaired their ability to perform more complex types of imagery. Given that patients with AD can perform basic mental imagery, our results suggest that episodic memory deficits likely prevent AD patients from storing or retrieving general mental images generated during encoding. Overall, the results of both experiments suggest that neurocognitive deficits do not allow patients with AD to perform complex mental imagery, which may be most beneficial to improving memory. However, our data also suggest that intact basic mental imagery and rehearsal could possibly be helpful if used in a rehabilitation multisession intervention approach.