Publications by authors named "Jason Brandt"

146 Publications

Dementia in late-onset epilepsy: The Atherosclerosis Risk in Communities study.

Neurology 2020 12 23;95(24):e3248-e3256. Epub 2020 Oct 23.

From the Departments of Neurology (E.L.H., G.L.K., M.S.A., K.A.W., R.F.G.), Psychiatry (J.B.), Medicine (S.Y.), and Epidemiology (R.F.G.), Johns Hopkins School of Public Health, Baltimore, MD; Department of Epidemiology (A.K.-N.), University of North Carolina at Chapel Hill; Department of Epidemiology (A.K.-N.), University of Kentucky, Lexington; Department of Neurology (D.S.K.), Mayo Clinic, Rochester; and N. Bud Grossman Center for Memory Research and Care (K.A.V.), Department of Neurology, and Institute for Translational Neuroscience (K.A.V.), University of Minnesota, Minneapolis.

Objective: To determine the risk of dementia after the development of late-onset epilepsy.

Methods: We used data from the Atherosclerosis Risk in Communities (ARIC) cohort study, which started in 1987 to 1989 with 15,792 mostly Black and White men and women from 4 US communities. We identified late-onset epilepsy (LOE; seizures starting at age 67 or later) from linked Medicare claims data. We used a Cox proportional hazards regression model to evaluate associations between LOE and dementia through 2017 as ascertained from neuropsychological testing, interviews, and hospital discharge surveillance, and we used multinomial logistic regression to assess the risk of dementia and mild cognitive impairment in the subset with full neuropsychological assessments available. We adjusted for demographics and vascular and Alzheimer disease risk factors.

Results: Of 9,033 ARIC participants with sufficient Medicare coverage data (4,980 [55.1%] female, 1993 [22.1%] Black), 671 met the definition of LOE. Two hundred seventy-nine (41.6%) participants with and 1,408 (16.8%) without LOE developed dementia ( < 0.001). After a diagnosis of LOE, the adjusted hazard ratio for developing subsequent dementia was 3.05 (95% confidence interval 2.65-3.51). The median time to dementia ascertainment after the onset of LOE was 3.66 years (quartile 1-3, 1.28-8.28 years).

Interpretation: The risk of incident dementia is substantially elevated in individuals with LOE. Further work is needed to explore causes for the increased risk of dementia in this growing population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836657PMC
December 2020

Late-onset epilepsy and 25-year cognitive change: The Atherosclerosis Risk in Communities (ARIC) study.

Epilepsia 2020 08 24;61(8):1764-1773. Epub 2020 Jul 24.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Objective: To define the association between late-onset epilepsy (LOE) and 25-year change in cognitive performance.

Methods: The Atherosclerosis Risk in Communities (ARIC) study is a multicenter longitudinal cohort study with participants from four U.S. communities. From linked Medicare claims, we identified cases of LOE, defined as ≥2 seizure-related diagnostic codes starting at age ≥67. The ARIC cohort underwent evaluation with in-person visits at intervals of 3-15 years. Cognition was evaluated 4 times over >25 years (including before the onset of seizures) using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT); a global z-score was also calculated. We compared the longitudinal cognitive changes of participants with and without LOE, adjusting for demographics and LOE risk factors.

Results: From 8033 ARIC participants with midlife cognitive testing and Medicare claims data available (4523 [56%] female, 1392 [17%] Black), we identified 585 cases of LOE. The rate of cognitive decline was increased on all measures in the participants who developed LOE compared to those without LOE. On the measure of global cognition, participants with LOE declined by -0.43 z-score points more over 25 years than did participants without epilepsy (95% confidence interval [CI] -0.59 to -0.27). Prior to the onset of seizures, cognitive decline was more rapid on the DWRT, DSST, and global z-scores in those who would later develop LOE than it was in non-LOE participants. Results were similar after excluding data from participants with dementia.

Significance: Global cognition, verbal memory, executive function, and word fluency declined faster over time in persons developing LOE than without LOE. Declines in cognition preceding LOE suggest these are linked; it will be important to investigate causes for midlife cognitive declines associated with LOE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718433PMC
August 2020

Diet in Brain Health and Neurological Disorders: Risk Factors and Treatments.

Authors:
Jason Brandt

Brain Sci 2019 Sep 13;9(9). Epub 2019 Sep 13.

Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

The role of nutrition in health and disease has been appreciated from time immemorial [...].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci9090234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770085PMC
September 2019

Identifying neuropsychologically impaired physicians.

Clin Neuropsychol 2020 02 19;34(2):318-331. Epub 2019 Sep 19.

Department of Psychiatry & Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

With the increasing focus on reducing medical errors and the aging of the physician workforce has come growing concern for cognitive impairment among physicians. This study sought to establish and validate an approach to detecting neuropsychological impairment among physicians. The neuropsychological test performance of 30 physicians referred clinically for neuropsychological evaluations was compared to that of 39 normal community-practicing urologists. We derived 9 key variables from the cognitive and motor tests as dependent variables. Impairment among the clinically-referred doctors was operationalized as scoring ≤5 percentile of the community physicians on at least 3, 4, 5, or 6 of the 9 variables. Using this approach, all clinically-referred physicians were classified as either "impaired" or "ambiguous." A cutoff of ≥5 impaired test scores provided the best balance among competing models. Using this criterion, 14 of the clinically-referred doctors (46%) were impaired and 16 remained ambiguous. The impaired physicians: (1) were older, (2) were more often suspected of having a neurodegenerative disorder, and (3) were more likely to have discontinued practicing medicine. These findings serve as initial validation of our methodology. Using conservative criteria derived from normal community physicians, we could identify a substantial subgroup of clinically-referred physicians who are unambiguously neurocognitively impaired. Replication and refinement of our method with larger samples are recommended, as are the development of specialty-specific criteria for impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2019.1666922DOI Listing
February 2020

Standardization of an Arabic-Language Neuropsychological Battery for Epilepsy Surgical Evaluations.

J Int Neuropsychol Soc 2019 08;25(7):761-771

Department of Psychiatry & Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: This study provides a standardized Arabic language neuropsychological test battery and tests its ability to distinguish patients with left and right hemisphere epileptic foci who are candidates for surgical resection.

Methods: An Arabic language battery of 15 tests was developed based on the neuropsychological test battery used at the Johns Hopkins Hospital for surgical evaluation of patients undergoing temporal lobe resection. With modifications where culturally required, 11 tests were translated to Arabic by the principal investigator and back-translated by two bilingual health professionals; four tests were available in Arabic and added to the battery. The battery was administered to 21 Arabic-speaking patients with left temporal epileptic foci, 21 with right temporal epileptic foci, and 46 neurologically and psychiatrically healthy adults.

Results: Nearly all the Arabic test versions were capable of differentiating healthy controls and the temporal lobe epilepsy (TLE) groups. Tests known to distinguish left and right temporal lobectomy candidates, such as wordlist memory and prose recall, were able to do so as accurately as the English versions. Also, a roughly "culturally free" task (the Baltimore Board) and a newly developed version of the Boston Naming Test demonstrated some sensitivity to left temporal lobe involvement.

Conclusions: Arabic-language neuropsychological tests for epilepsy surgical evaluations are made available, demonstrate cultural sensitivity and clinical validity, and require further psychometric property and normative research. (JINS, 2019, 25, 761-771).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617719000432DOI Listing
August 2019

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease.

Parkinsonism Relat Disord 2019 07 16;64:235-241. Epub 2019 Apr 16.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism.

Methods: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4-6 months of STN stimulation in seven PD patients (mean age 67 ± 7).

Results: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism.

Conclusions: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2019.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304230PMC
July 2019

Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease.

J Alzheimers Dis 2019 ;68(3):969-981

Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ketone bodies, the products of fat metabolism, are a source of energy for the brain and are available even when glucose supplies are inadequate (such as with severe carbohydrate deprivation) or its metabolism is faulty (as it is in Alzheimer's disease). This phase I/II randomized clinical trial examined the feasibility of using a modified Atkins diet (MAD) to induce ketogenesis in persons with mild cognitive impairment (MCI) or early AD, and the effect of this diet on memory and other clinical outcomes. In the first 2.5 years of active recruitment, only 27 eligible and willing patients enrolled. After extensive assessment and education, they and their study partners were randomly assigned for 12 weeks to either the MAD or the National Institute on Aging (NIA) recommended diet for seniors. As of April 2018, 9 patients in the MAD arm and 5 in the NIA arm have completed the trial. In spite of extensive teaching, coaching, and monitoring, adherence to both diets was only fair. Among those in the MAD arm who generated at least trace amounts of urinary ketones, there was a large (effect size = 0.53) and statistically significant (p = 0.03) increase in Memory Composite Score between the baseline and week-6 assessment. MAD participants also reported increased energy between baseline and week-6 assessment. Despite challenges to implementing this trial, resulting in a small sample, our preliminary data suggest that the generation of even trace ketones might enhance episodic memory and patient-reported vitality in very early AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-180995DOI Listing
August 2020

Influence of sex differences in interpreting learning and memory within a clinical sample of older adults.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2020 01 20;27(1):18-39. Epub 2019 Jan 20.

Neurological Institute, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, USA.

Sex is an important factor to consider when evaluating memory with older adults. This present study aimed to examine sex differences in memory within a clinical sample of older adults ( = 1084). Raw learning and recall scores on the Hopkins Verbal Learning Test, Revised (HVLT-R) and Brief Visuospatial Memory Test, Revised (BVMT-R) were compared between sexes within the entire sample and cohorts stratified by age. Within the entire sample, women outperformed men in HVLT-R learning and recall, and there were no sex differences in BVMT-R performance. These sex differences, however, were absent or reversed for those with impaired HVLT-R performance and functional deficits, indicating that women retain an early advantage in verbal memory, which is lost with greater indication of disease severity. These findings indicate that women retain an advantage in verbal learning and memory, at least before significant levels of impairment, within a sample of older adults seen at an outpatient neurology clinic, which may have implications for diagnosing memory disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13825585.2019.1566433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677625PMC
January 2020

Risk perception before and after presymptomatic genetic testing for Huntington's disease: Not always what one might expect.

Mol Genet Genomic Med 2018 11 4;6(6):1140-1147. Epub 2018 Nov 4.

Berman Institute of Bioethics, Johns Hopkins University, Baltimore, Maryland.

Background: In 1983, Huntington's disease (HD) was the first genetic disease mapped using DNA polymorphisms. Shortly thereafter, presymptomatic genetic testing for HD began in the context of two research studies. One of these trials was at the Johns Hopkins University Huntington's Disease Center.

Methods: As part of the protocol, risk perception (RP) values were collected at 16 time points before and after testing. The current study investigated changes in RP scores before and after genetic testing. Of the 186 participants with pre- and post-testing RP values, 39 also had contemporaneous research clinic notes and recent semi-structured interviews available for analysis.

Results: The data reveal tremendous diversity in RP. While the RP scores of most individuals change in the way one would expect, 27% of participants demonstrated unexpected changes in RP after disclosure. A significantly higher proportion of individuals who received an expanded repeat result had unexpected changes in RP, compared with those who received normal repeat results.

Conclusions: The data suggest that individuals' RP is influenced by more than merely the results of genetic testing. This finding is important for genetic counselors and healthcare providers, as it suggests that even comprehensive patient education and disclosure of genetic test results may not ensure that people fully appreciate their disease risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305678PMC
November 2018

Neuropsychological predictors of patient-reported cognitive decline after deep brain stimulation in Parkinson's disease.

J Clin Exp Neuropsychol 2019 04 8;41(3):219-228. Epub 2018 Oct 8.

a Department of Neurology , The Johns Hopkins University School of Medicine , Baltimore , MD , USA.

Background: Deep brain stimulation (DBS) is effective for treatment of motor complications of dopaminergic therapy in Parkinson's disease (PD) but occasionally has been associated with multidomain cognitive decline. Patient- and caregiver-reported cognitive decline are clinically meaningful and increasingly recognized as important to consider when evaluating therapeutic interventions for PD.

Objective: The objective was to assess presurgical neuropsychological and clinical factors associated with PD patient- and caregiver-reported cognitive decline in two or more domains after DBS.

Method: A single telephone survey was used to assess patient- and caregiver-reported cognitive decline in five domains at both one and four months after DBS surgery. Decline in two or more domains was considered multidomain cognitive decline (MDCD). Baseline demographic, clinical, and neuropsychological factors were compared in those with or without MDCD. Preoperative neuropsychological measures were evaluated as risk factors and regressed on the presence of MDCD, with demographic covariates, using multiple logistic regression.

Results: Preoperative performance in verbal recognition memory, language knowledge, and verbal processing decline were associated with postoperative, patient-reported MDCD in the first four weeks. MDCD at four months after DBS was associated with worse preoperative verbal reasoning, verbal recall, and semantic verbal fluency. Caregiver-reported MDCD one month after DBS was associated with poorer baseline verbal memory recognition accuracy/discriminability, visuospatial problem solving, and constructional praxis.

Conclusion: Poor presurgical performance in verbal memory recognition, language processing, and visuospatial performance is associated with patient- or caregiver-reported decline following DBS surgery. Posterior cortical dysfunction seems to portend significant self-reported cognitive decline following deep brain stimulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13803395.2018.1526889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380950PMC
April 2019

Behavioral Changes in Huntington Disease

Authors:
Jason Brandt

Cogn Behav Neurol 2018 03;31(1):26-35

Department of Psychiatry and Behavioral Sciences, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNN.0000000000000147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005379PMC
March 2018

Regio- and Stereoselective Hydroamination of Alkynes Using an Ammonia Surrogate: Synthesis of N-Silylenamines as Reactive Synthons.

J Am Chem Soc 2018 04 5;140(15):4973-4976. Epub 2018 Apr 5.

Department of Chemistry , University of British Columbia , 2036 Main Mall , Vancouver , British Columbia , Canada V6T 1Z1.

An anti-Markovnikov selective hydroamination of alkynes with N-silylamines to afford N-silylenamines is reported. The reaction is catalyzed by a bis(amidate)bis(amido)Ti(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting N-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.7b13783DOI Listing
April 2018

Neuropsychological investigation of "the amazing memory man".

Neuropsychology 2018 03 21;32(3):304-316. Epub 2017 Dec 21.

Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine.

Objective: Mnemonists, memory champions, and persons with highly superior autobiographical memory (HSAM) are apparently rare breeds, with no more than a few dozen cases of each described in the neuroscientific literature. This report describes a newly discovered HSAM case who has extraordinary memory for a wider range of material than has heretofore been described.

Method: Subject MM was interviewed about his personal life and administered standard clinical tests of cognition and personality, as well as experimental tasks assessing personal and generic episodic and semantic memory. Finally, he was studied with high resolution structural MRI of the medial temporal lobes, as well as brain connectivity analysis using resting-state functional MRI.

Results: MM's ability to recall general factual information, historical facts and dates, sports statistics, and popular culture, as well as personal life experiences, is exceptional, even though he performs in only the average range on tests of intellect and new learning ability. Unlike most mnemonists, he denies using any specific mnemonic strategy and, unlike many other HSAM cases, is unable to recall highly specific details of days in his adult life. Structural brain imaging in MM reveals atypical anatomy in his left temporal lobe, and functional neuroimaging suggests greater than usual connectivity of the left hippocampus with premotor, prefrontal and retrosplenial cingulate cortex.

Conclusions: These observations are discussed in the context of previous studies of mnemonists and HSAM cases, some of which implicate hyperconnectivity among components of an expanded memory network in extraordinary memory retrieval. (PsycINFO Database Record
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/neu0000410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441970PMC
March 2018

Molecular imaging of serotonin degeneration in mild cognitive impairment.

Neurobiol Dis 2017 Sep 13;105:33-41. Epub 2017 May 13.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic areas typically affected by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum and thalamus that are relatively spared in Alzheimer's disease. The reduction of the serotonin transporter in mild cognitive impairment was greater than grey matter atrophy or reductions in regional cerebral blood flow compared to controls. Lower cortical serotonin transporters were associated with worse performance on tests of auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. The serotonin system may represent an important target for prevention and treatment of MCI, particularly the post-synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as presynaptic aspects of the serotonin system, as indicated by the observation of lower serotonin transporters in MCI relative to healthy controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2017.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663212PMC
September 2017

Association between serotonin denervation and resting-state functional connectivity in mild cognitive impairment.

Hum Brain Mapp 2017 Jul 5;38(7):3391-3401. Epub 2017 Apr 5.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting-state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting-state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting-state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting-state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI. Hum Brain Mapp 38:3391-3401, 2017. © 2017 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.23595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628094PMC
July 2017

Brief Report: Using the Internet to Identify Persons with Cognitive Impairment for Participation in Clinical Trials.

Brain Sci 2017 Apr 5;7(4). Epub 2017 Apr 5.

The Johns Hopkins University School of Medicine, Psychiatry and Behavioral Sciences, Division of Medical Psychology, The Johns Hopkins Hospital, 600 North Wolfe Street, Meyer 218, Baltimore, MD 21287-7218, USA.

Identifying, recruiting, and enrolling persons in clinical trials of dementia treatments is extremely difficult. One approach to first-wave screening of potential participants is the use of online assessment tools. Initial studies using the Dementia Risk Assessment (DRA)-which includes a previously validated recognition memory test-support the use of this self-administered assessment to identify individuals with "suspected MCI" or "suspected dementia." In this study, we identified between 71 and 622 persons with suspected dementia and between 128 and 1653 persons with suspected mild cognitive impairment (depending on specific criteria) over the course of 22 months. Assessment tools that can inexpensively and easily identify individuals with higher than average risk for cognitive impairment can facilitate recruitment for large-scale clinical trials for dementia treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci7040036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406693PMC
April 2017

Neuropsychiatric Complications of Parkinson Disease Treatments: Importance of Multidisciplinary Care.

Am J Geriatr Psychiatry 2016 12 3;24(12):1171-1180. Epub 2016 Sep 3.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins Hospital, Baltimore, MD. Electronic address:

Although Parkinson disease (PD) is defined clinically by its motor symptoms, it is increasingly recognized that much of the disability and worsened quality of life experienced by patients with PD is attributable to psychiatric symptoms. The authors describe a model of multidisciplinary care that enables these symptoms to be effectively managed. They describe neuropsychiatric complications of PD itself and pharmacologic and neurostimulation treatments for parkinsonian motor symptoms and discuss the management of these complications. Specifically, they describe the clinical associations between motor fluctuations and anxiety and depressive symptoms, the compulsive overuse of dopaminergic medications prescribed for motor symptoms (the dopamine dysregulation syndrome), and neuropsychiatric complications of these medications, including impulse control disorders, psychosis, and manic syndromes. Optimal management of these problems requires close collaboration across disciplines because of the potential for interactions among the pathophysiologic process of PD, motor symptoms, dopaminergic drugs, and psychiatric symptoms. The authors emphasize how their model of multidisciplinary care facilitates close collaboration among psychiatrists, other mental health professionals, neurologists, and functional neurosurgeons and how this facilitates effective care for patients who develop the specific neuropsychiatric complications discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jagp.2016.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136297PMC
December 2016

Cognitive impairment in Parkinson's disease: Association between patient-reported and clinically measured outcomes.

Parkinsonism Relat Disord 2016 12 27;33:107-114. Epub 2016 Sep 27.

Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, 10751 Fall Road, Suite 250, Lutherville, MD 21093, Baltimore, MD, United States.

Background: In Parkinson's disease, the association between objective and patient-reported measures of cognitive dysfunction is unknown and highly relevant to research and clinical care.

Objective: To determine which cognitive domain-specific Montreal Cognitive Assessment (MoCA) subscores are most strongly associated with patient-reported cognitive impairment on question 1 (Q1) of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

Methods: We analyzed data from 759 PD participants and 481 persons without PD with in a retrospective, cross sectional analysis using data from the NINDS Parkinson's Disease Biomarkers Program (PDBP), a longitudinal, multicenter biomarker study. The relationship between a patient-reported cognitive rating (MDS-UPDRS q1.1) and objective cognitive assessments (MoCA) was assessed using multinomial logistic regression modeling and the outcomes reported as conditional odds ratios (cOR's) representing the relative odds of a participant reporting cognitive impairment that is "slight" versus "normal" on MDS-UPDRSq1.1 for a one unit increase in a MoCA sub-score, adjusted for age and education.

Results: In PD participants, changes in visuospatial-executive performance and memory had the most significant impact on subjective cognitive impairment. A 1-point increase in visuospatial-executive function decreased the chance of reporting a MDS-UPDRS Q1 score of "slight" versus "normal" by a factor of 0.686 (p < 0.001) and each 1 point improvement in delayed recall decreased the odds of reporting "slight" cognitive impairment by a factor of 0.836 (p < 0.001).

Conclusions: Conversion from a PD patient's report of "normal" to "slight" cognitive impairment may be associated with changes in visuospatial-executive dysfunction and memory more than other cognitive domains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2016.09.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154808PMC
December 2016

Response to Bodin and Grote regarding postdoctoral recruitment in clinical neuropsychology.

Clin Neuropsychol 2016 07 31;30(5):651-9. Epub 2016 May 31.

j Department of Clinical & Health Psychology , University of Florida , Gainesville , FL , USA.

Bodin and Grote convey their opinion that the field of clinical neuropsychology would be best served by a match system for recruitment into postdoctoral training. We critically review their arguments and offer an alternative point of view. Our view considers the current state of the match system in neuropsychology, incorporates comparisons with other disciplines that rely on a match system, and addresses the role of postdoctoral training and the specialization that takes shape at this level. We make recommendations aimed at promoting greater unity among postdoctoral training programs with the goal of focusing leadership efforts on advancing our shared mission of providing the highest quality training in clinical neuropsychology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2016.1188990DOI Listing
July 2016

Behavioral Ratings of Executive Functioning Explain Instrumental Activities of Daily Living beyond Test Scores in Parkinson's Disease.

Clin Neuropsychol 2016 20;30(1):95-106. Epub 2016 Jan 20.

a Department of Psychiatry and Behavioral Sciences , Johns Hopkins University School of Medicine , Baltimore , MD , USA.

Objective: Executive dysfunction is common in Parkinson's disease (PD), yet the relationship between executive functioning (EF) and instrumental activities of daily living (IADLs) is inconsistent. This inconsistency may be due to the limited relationship between EF test scores and behaviors. Rating scales provide a potential way to supplement test scores in predicting patient's ability to complete IADLs by capturing a wide range of EF behaviors in their everyday environment. We hypothesized that informant-rated EF would provide incremental validity in predicting IADLs above and beyond EF test scores.

Methods: Eighty-five patients were selected from a clinical neuropsychological database of PD patients evaluated for deep brain stimulation surgery at The Johns Hopkins Hospital between September 2006 and January 2015. Hierarchical regression was completed to determine the relationship between an EF behavioral rating scale (i.e., FrSBe), EF test scores, and IADLs.

Results: The EF behavioral rating scale added incremental validity to neuropsychological test scores in predicting IADLs.

Conclusions: Behavioral ratings of EF may provide additional information about how PD patients' EF is influencing their everyday life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2015.1133847DOI Listing
October 2016

Harmonizing Measures of Cognitive Performance Across International Surveys of Aging Using Item Response Theory.

J Aging Health 2015 Dec;27(8):1392-414

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Objective: To harmonize measures of cognitive performance using item response theory (IRT) across two international aging studies.

Method: Data for persons ≥65 years from the Health and Retirement Study (HRS, N = 9,471) and the English Longitudinal Study of Aging (ELSA, N = 5,444). Cognitive performance measures varied (HRS fielded 25, ELSA 13); 9 were in common. Measurement precision was examined for IRT scores based on (a) common items, (b) common items adjusted for differential item functioning (DIF), and (c) DIF-adjusted all items.

Results: Three common items (day of date, immediate word recall, and delayed word recall) demonstrated DIF by survey. Adding survey-specific items improved precision but mainly for HRS respondents at lower cognitive levels.

Discussion: IRT offers a feasible strategy for harmonizing cognitive performance measures across other surveys and for other multi-item constructs of interest in studies of aging. Practical implications depend on sample distribution and the difficulty mix of in-common and survey-specific items.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0898264315583054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834843PMC
December 2015

The Unique and Combined Effects of Apathy and Depression on Cognition in Parkinson's Disease.

J Parkinsons Dis 2015 ;5(2):351-9

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Apathy and depression are associated with poor cognition in patients with Parkinson's disease (PD). However, the cognitive signature of each syndrome is not well understood. The cognitive consequences of having apathy or depression, versus apathy and depression, are also unclear.

Objective: This study investigated the unique and combined effects of apathy and depression on cognition in PD patients.

Methods: PD patients were identified from a clinical research database as having self-reported apathy (n = 21), depression (n = 11), or both (n = 43). PD patients without apathy or depression served as the Control group (n = 49). The groups were of similar age, education, disease severity, age of symptom onset, and medication status. A multivariate analysis of variance (MANOVA) compared the groups on 17 neuropsychological test scores in the domains of attention, motor and psychomotor speed, construction, language, episodic memory, and executive functioning.

Results: There was a significant overall effect of group: F(18,276) = 2.12, p = 0.006, ηp2=0.12. Univariate analyses and planned contrasts revealed medium-sized effects distinguishing only the control group and the group with both apathy and depression (ηp2=0.06-0.12) on measures of verbal fluency and manual, processing, and psychomotor speed.

Conclusions: PD patients with apathy alone or depression alone did not perform worse than PD controls on neuropsychological tests. Patients with apathy and depression performed worse than controls, but only on speed-based measures. This suggests that apathy and depression are associated with the same or similar circuits as those of cognitive and motor speed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JPD-140484DOI Listing
June 2016

Objectively Measured Sleep and β-amyloid Burden in Older Adults: A Pilot Study.

SAGE Open Med 2014 Aug;2

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD ; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD.

Background/aims: Although disturbed sleep is associated with cognitive deficits, the association between sleep disturbance and Alzheimer's disease (AD) pathology is unclear. In this pilot study, we examined the extent to which sleep duration, sleep quality, and sleep-disordered breathing (SDB) are associated with β-amyloid (Aβ) deposition in the brains of living humans.

Methods: We studied 13 older adults (8 with normal cognition and 5 with mild cognitive impairment (MCI)). Participants completed neuropsychological testing, polysomnography and Aβ imaging with [C]-Pittsburgh compound B.

Results: Among participants with MCI, higher apnea-hypopnea index and oxygen desaturation index were associated with greater Aβ deposition, globally and regionally in the precuneus. There were no significant associations between SDB and Aβ deposition among cognitively normal participants. There were no significant associations between sleep duration or sleep fragmentation and Aβ deposition.

Conclusion: These preliminary results suggest that, among older adults with MCI, greater SDB severity is associated with greater Aβ deposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304392PMC
http://dx.doi.org/10.1177/2050312114546520DOI Listing
August 2014

Betting on DBS: Effects of subthalamic nucleus deep brain stimulation on risk taking and decision making in patients with Parkinson's disease.

Neuropsychology 2015 Jul 8;29(4):622-631. Epub 2014 Dec 8.

Department of Neurology.

Objective: Concerns persist that deep brain stimulation (DBS) for Parkinson's disease (PD) increases impulsivity or induces excessive reward seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on 3 laboratory tasks of risk taking and decision making. They are compared with PD patients maintained on medication and healthy participants.

Methods And Results: In the Game of Dice Task, a test of "risky" decision making, PD patients with or without DBS made highest risk bets more often and ended up with less money than did healthy participants. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an "ambiguous" decision-making task that assessed preference for risk (holding on to one's briefcase) over a "sure thing" (accepting the banker's offer). Here, DBS patients were more conservative with stimulation on than with it off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the 2 PD groups won less money than did healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was "framed" as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than were healthy participants, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation.

Conclusions: On risky decision-making tasks, DBS patients took more risks than did healthy participants, but stimulation may temper this tendency. In contrast, in an ambiguous-risk situation, DBS patients were more risk-averse (conservative) than were healthy participants, and this tendency was greatest with stimulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/neu0000164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459935PMC
July 2015

Determinants of functional disability in Huntington's disease: role of cognitive and motor dysfunction.

Mov Disord 2014 Sep;29(11):1351-8

Division of Neurobiology, Department of Psychiatry, Departments of Neurology, Neuroscience, and Pharmacology, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The clinical syndrome of Huntington's disease (HD) is notable for a triad of motor, cognitive, and emotional features. All HD patients eventually become occupationally disabled; however, the factors that render HD patients unable to maintain employment have not been extensively studied. This review begins by discussing the clinical triad of HD, highlighting the distinction in the motor disorder between involuntary movements, such as chorea, and voluntary movement impairment, with the latter contributing more to functional disability. Cognitive disorder clearly contributes to disability, though the relative contribution compared to motor is difficult to unravel, especially because many of the tests used to asses "cognition" have a strong motor component. The role of emotional changes in disability needs more study. The literature on contributions to functional disability, driving impairment, and nursing home placement is reviewed. Relevant experience is presented from the long-standing JHU HD observational study on motor versus cognitive onset, as well as on cognitive and motor features at the time when individuals discontinued working. Finally, we briefly review government policies in several countries on disability determination. We interpret the data from our own studies and from the literature to indicate that there is usually a close relationship between cognitive and motor dysfunction, and that it is critical to take both into consideration in determining disability. © 2014 International Parkinson and Movement Disorder Society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.26012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197404PMC
September 2014

2-Pyridonate tantalum complexes for the intermolecular hydroaminoalkylation of sterically demanding alkenes.

J Am Chem Soc 2014 Aug 23;136(31):10898-901. Epub 2014 Jul 23.

Department of Chemistry, University of British Columbia , 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1.

The design and synthesis of a mixed 2-pyridonate-Ta(NMe2)3Cl complex for the direct C-H alkylation adjacent to nitrogen in unprotected secondary amines are reported. The hydroaminoalkylation of sterically demanding internal alkenes gives the direct, catalytic formation of C(sp(3))-C(sp(3)) bonds. Substrate scope investigations reveal key strategies for further catalyst development efforts in this 100% atom-economic synthesis of α-alkylated amines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/ja506187mDOI Listing
August 2014

Further validation of the Internet-based Dementia Risk Assessment.

J Alzheimers Dis 2014 ;41(3):937-45

Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.

Most approaches to the detection of presymptomatic or prodromal Alzheimer's disease require the costly collection and analysis of biological samples or neuroimaging measurements. The Dementia Risk Assessment (DRA) was developed to facilitate this detection by collecting self-report and proxy-report of dementia risk variables and episodic memory performance on a free Internet website. We now report two validation studies. In Study 1, 130 community-residing older adults seeking memory screening at senior health fairs were tested using the Mini-Cog, and were then observed while taking the DRA. They were compared to a demographically-matched subsample from our anonymous Internet sample. Participants seeking memory screening had more dementia risk factors and obtained lower scores on the DRA's recognition memory test (RMT) than their Internet controls. In addition, those who failed the Mini-Cog obtained much lower scores on the RMT than those who passed the Mini-Cog. In Study 2, 160 older adults seeking evaluation of cognitive difficulties took the DRA prior to diagnostic evaluations at outpatient dementia clinics. Patients who ultimately received the diagnosis of a dementia syndrome scored significantly lower on the RMT than those diagnosed with other conditions or deemed normal. Lower education, family history of dementia, presence of hypercholesterolemia and diabetes, and memory test score distinguished the dementia and no-dementia groups with around 82% accuracy. In addition, score on the RMT correlated highly with scores on other instruments widely used to detect cognitive decline. These findings support the concurrent validity of the DRA for detecting prevalent cognitive impairment. Prospective studies of cognitively normal persons who subsequently develop dementia will be necessary to establish its predictive validity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-140297DOI Listing
September 2015

Social cognition in Alzheimer's disease: a separate construct contributing to dependence.

Alzheimers Dement 2014 Nov 18;10(6):818-26. Epub 2014 Mar 18.

Cognitive Neuroscience Division, Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY, USA.

The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD. Participants were monitored every 6 months for 5.5 years. Results from multivariate latent growth curve models adjusted for sex, age, education, depression, and recruitment site revealed that social cognition and general cognition were unrelated cross-sectionally and throughout time. However, baseline levels of each were related independently to dependence, and change values of each were related independently to change in dependence. These findings highlight the separability of social and general cognition in AD. Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jalz.2013.12.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980672PMC
November 2014

Health-care use and cost in dementia caregivers: Longitudinal results from the Predictors Caregiver Study.

Alzheimers Dement 2015 Apr 15;11(4):444-54. Epub 2014 Mar 15.

Cognitive Neuroscience Division of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA.

Objective: To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost.

Methods: One hundred forty-seven caregiver/patient dyads were followed annually for 6 years in three academic Alzheimer's disease centers in the United States. Logistic, negative binomial, and generalized linear mixed models were used to examine overall effects of caregiver/patient characteristics on caregivers' hospitalizations, doctor visits, outpatient tests and procedures, and prescription and over-the-counter medications.

Results: Patients' comorbid conditions and dependence were associated with increased health-care use and costs of caregivers. Increases in caregiver depressive symptoms are associated with increases in multiple domains of caregivers' health-care use and costs.

Discussion: Findings suggest expanding our focus on dementia patients to include family caregivers to obtain a fuller picture of effects of caregiving. Primary care providers should integrate caregivers' needs in health-care planning and delivery. Clinical interventions that treat patients and caregivers as a whole will likely achieve the greatest beneficial effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jalz.2013.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164583PMC
April 2015

Do older adults use the method of loci? Results from the ACTIVE study.

Exp Aging Res 2014 ;40(2):140-63

a Department of Mental Health , Johns Hopkins Bloomberg School of Public Health , Baltimore , Maryland , USA.

Unlabelled: BACKGROUND/STUDY CONTEXT: The method of loci (MoL) is a complex visuospatial mnemonic strategy. Previous research suggests that older adults could potentially benefit from using the MoL, but that it is too attentionally demanding for them to use in practice. The authors evaluated the hypotheses that training can increase the use of MoL, and that MoL use is associated with better memory.

Methods: The authors analyzed skip patterns on response forms for the Auditory Verbal Learning Test (AVLT) in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE; N = 1401) trial using 5 years of longitudinal follow-up.

Results: At baseline, 2% of participants skipped spaces. Fewer than 2% of control participants skipped spaces at any visit across 5 years, but 25% of memory-trained participants, taught the MoL, did so. Participants who skipped spaces used more serial clustering, a hallmark of the MoL (p < .001). Trained participants who skipped spaces showed greater memory improvement after training than memory-trained participants who did not skip spaces (Cohen's d = .84, p = .007), and did not differ in the subsequent rate of long-term memory decline through up to 5 years of follow-up.

Conclusion: Despite being attentionally demanding, this study suggests that after training, the MoL is used by up to 25% of older adults, and that its use is associated with immediate memory improvement that was sustained through the course of follow-up. Findings are consistent with the notion that older adults balance complexity with novelty in strategy selection, and that changes in strategies used following memory training result in observable qualitative and quantitative differences in memory performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0361073X.2014.882204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955885PMC
November 2014