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

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.

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

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).

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

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.

Molecular imaging of serotonin degeneration in mild cognitive impairment.

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.

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

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.

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

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.

Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis.

Half of all patients with multiple sclerosis (MS) experience cognitive impairment, for which there is no pharmacological treatment. Using magnetic resonance spectroscopy (MRS), we examined metabolic changes in the hippocampi of MS patients, compared the findings to performance on a neurocognitive test battery, and found that N-acetylaspartylglutamate (NAAG) concentration correlated with cognitive functioning. Specifically, MS patients with cognitive impairment had low hippocampal NAAG levels, whereas those with normal cognition demonstrated higher levels. We then evaluated glutamate carboxypeptidase II (GCPII) inhibitors, known to increase brain NAAG levels, on cognition in the experimental autoimmune encephalomyelitis (EAE) model of MS. Whereas GCPII inhibitor administration did not affect physical disabilities, it increased brain NAAG levels and dramatically improved learning and memory test performance compared with vehicle-treated EAE mice. These data suggest that NAAG is a unique biomarker for cognitive function in MS and that inhibition of GCPII might be a unique therapeutic strategy for recovery of cognitive function.

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

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.

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

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.

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

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.

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

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.

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

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.

The impact of complex chronic diseases on care utilization among assisted living residents.

PURPOSE: Many residents of assisted living (AL) have chronic diseases that are difficult to manage, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). We estimated the amount and intensity of care delivered by the staff for residents with these conditions. METHODS: We performed a secondary data analysis from the Maryland Assisted Living (MDAL) Study (399 residents, 29 facilities). In-person assessments included measures of cognition, function, depression, and general medical health. Diagnosis of CHF, COPD, and DM, as well as current medications was abstracted from AL medical charts. Measures of care utilization were operationalized at the resident level as: 1) minutes per day of direct care (caregiver activity scale [CAS]), 2) subjective staff ratings of care burden, and 3) assigned AL "level of care" (based on state regulatory criteria). RESULTS: In best fit regression models, CHF and DM were not significant predictors of the evaluated care utilization measures; however, COPD was independently associated with increased minutes per day of direct care - 34% of the variance in the caregiver activity scale was explained by degree of functional dependency, cognitive impairment, age, and presence of COPD. Functional dependency, depressive symptoms, and age explained almost a quarter (23%) of the variance of staff care burden rating. For the AL level of care intensity rating, degree of functional dependency, level of cognition, and age were significant correlates, together explaining about 28% of the variance. CONCLUSION: The presence of COPD was a significant predictor of time per day of direct care. However, CHF and DM were not correlates of care utilization measures. Functional and cognitive impairment was associated with measures of care utilization, reiterating the importance of these characteristics in the utilization and intensity of care consumed by AL residents. Further study of this population could reveal other forms and amounts of care utilization.

A randomized feasibility trial of the modified Atkins diet in older adults with mild cognitive impairment due to Alzheimer's disease.

Background: Alzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action. Methods: We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time. Results: A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: -0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen's D = 0.57, 95% CI: -0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids. Conclusions: Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

New antiepileptic drug safety information is not transmitted systematically and accepted by U.S. neurologists.

We surveyed U.S. neurologists in order to evaluate their knowledge of, and sources for, recent FDA safety warnings regarding antiepileptic drugs (AEDs) and whether they incorporate this information into their practices. Survey respondents (N=505) were predominantly board-certified American Academy of Neurology members. Approximately 20% of respondent neurologists were not aware of warnings about four drug safety risks: suicidality with newer AEDs, increased birth defect risks from in utero divalproex exposure, impaired cognitive development from in utero divalproex exposure, and the requirement of haplotype screening in patients of Asian descent starting carbamazepine. Most respondents were aware of a recommendation for haplotype screening, yet did not routinely perform the safety screening, and 18 reported patients that had hypersensitivity reactions to carbamazepine. Respondents learned about drug safety risks from varied sources; only notifications from specialty organizations were associated with accurate knowledge of drug safety warnings. Most surveyed neurologists would prefer implementing "a formal warning process via specialty organizations" with e-mails of updated product insert warnings.

Cohort differences in dementia recognition and treatment indicators among assisted living residents in Maryland: did a change in the resident assessment tool make a difference?

BACKGROUND: There is a lack of empirical evidence about the impact of regulations on dementia care quality in assisted living (AL). We examined cohort differences in dementia recognition and treatment indicators between two cohorts of AL residents with dementia, evaluated prior to and following a dementia-related policy modification to more adequately assess memory and behavioral problems. METHODS: Cross-sectional comparison of two AL resident cohorts was done (Cohort 1 [evaluated 2001-2003] and Cohort 2 [evaluated 2004-2006]) from the Maryland Assisted Living studies. Initial in-person evaluations of residents with dementia (n = 248) were performed from a random sample of 28 AL facilities in Maryland (physician examination, clinical characteristics, and staff and family recognition of dementia included). Adequacy of dementia workup and treatment was rated by an expert consensus panel. RESULTS: Staff recognition of dementia was better in Cohort 1 than in Cohort 2 (77% vs. 63%, p = 0.011), with no significant differences in family recognition (86% vs. 85%, p = 0.680), or complete treatment ratings (52% vs. 64%, p = 0.060). In adjusted logistic regression, cognitive impairment and neuropsychiatric symptoms correlated with staff recognition; and cognitive impairment correlated with family recognition. Increased age and cognitive impairment reduced odds of having a complete dementia workup. Odds of having complete dementia treatment was reduced by age and having more depressive symptoms. Cohort was not predictive of dementia recognition or treatment indicators in adjusted models. CONCLUSIONS: We noted few cohort differences in dementia care indicators after accounting for covariates, and concluded that rates of dementia recognition and treatment did not appear to change much organically following the policy modifications.

12-month incidence, prevalence, persistence, and treatment of mental disorders among individuals recently admitted to assisted living facilities in Maryland.

BACKGROUND: To estimate the 12-month incidence, prevalence, and persistence of mental disorders among recently admitted assisted living (AL) residents and to describe the recognition and treatment of these disorders. METHODS: Two hundred recently admitted AL residents in 21 randomly selected AL facilities in Maryland received comprehensive physician-based cognitive and neuropsychiatric evaluations at baseline and 12 months later. An expert consensus panel adjudicated psychiatric diagnoses (using DSM-IV-TR criteria) and completeness of workup and treatment. Incidence, prevalence, and persistence were derived from the panel's assessment. Family and direct care staff recognition of mental disorders was also assessed. RESULTS: At baseline, three-quarters suffered from a cognitive disorder (56% dementia, 19% Cognitive Disorders Not Otherwise Specified) and 15% from an active non-cognitive mental disorder. Twelve-month incidence rates for dementia and non-cognitive psychiatric disorders were 17% and 3% respectively, and persistence rates were 89% and 41% respectively. Staff recognition rates for persistent dementias increased over the 12-month period but 25% of cases were still unrecognized at 12 months. Treatment was complete at 12 months for 71% of persistent dementia cases and 43% of persistent non-cognitive psychiatric disorder cases. CONCLUSIONS: Individuals recently admitted to AL are at high risk for having or developing mental disorders and a high proportion of cases, both persistent and incident, go unrecognized or untreated. Routine dementia and psychiatric screening and reassessment should be considered a standard care practice. Further study is needed to determine the longitudinal impact of psychiatric care on resident outcomes and use of facility resources.

Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer's disease.

OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores ≥ 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score ≤ 10) and functional (Blessed Dementia Rating Scale score ≥ 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects.

Thin-Film Organic Heteroepitaxy.

Incorporating crystalline organic semiconductors into electronic devices requires understanding of heteroepitaxy given the ubiquity of heterojunctions in these devices. However, while rules for commensurate epitaxy of covalent or ionic inorganic material systems are known to be dictated by lattice matching constraints, rules for heteroepitaxy of molecular systems are still being written. Here, it is found that lattice matching alone is insufficient to achieve heteroepitaxy in molecular systems, owing to weak intermolecular forces that describe molecular crystals. It is found that, in addition, the lattice matched plane also must be the lowest energy surface of the adcrystal to achieve one-to-one commensurate molecular heteroepitaxy over a large area. Ultraviolet photoelectron spectroscopy demonstrates the lattice matched interface to be of higher electronic quality than a disordered interface of the same materials.