Chiadi U. Onyike

The epidemiology of frontotemporal dementia

Abstract Frontotemporal dementia, a heterogeneous neurodegenerative disorder, is a common cause of young onset dementia (i.e. dementia developing in midlife or earlier). The estimated point prevalence is 15–22/100,000, and incidence 2.7–4.1/100,000. Some 25% are late-life onset cases. Population studies show nearly equal distribution by gender, which contrasts with myriad clinical and neuropathology reports. FTD is frequently familial and hereditary; five genetic loci for causal mutations have been identified, all showing 100% penetrance. Non-genetic risk factors are yet to be identified. FTD shows poor life expectancy but with survival comparable to that of Alzheimers disease. Recent progress includes the formulation of up-to-date diagnostic criteria for the behavioural and language variants, and the development of new and urgently needed instruments for monitoring and staging the illness. There is still need for descriptive population studies to fill gaps in our knowledge about minority groups and developing regions. More pressing, however, is the need for reliable physiological markers for disease. There is a present imperative to develop a translational science to form the conduit for transferring neurobiological discoveries and insights from bench to bedside.

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

BACKGROUND The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes. OBJECTIVE To characterize clinical, diagnostic, and molecular features of 5 sCJD variants. DESIGN Retrospective analysis. SETTING The Johns Hopkins and Veterans Administration health care systems. PARTICIPANTS Eighty-eight patients with definite or probable sCJD. MAIN OUTCOME MEASURES Differences in age at onset, illness progression, diagnostic test results, and molecular subtype. RESULTS The age at onset differed among sCJD variants (P = .03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P < .001) and the time to clinical presentation (P = .003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P = .004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/methionine type 1 molecular subtype. CONCLUSIONS The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Consensus classification of posterior cortical atrophy

A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.

Apathy associated with neurocognitive disorders: Recent progress and future directions

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimers disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities.

Improper Sexual Behaviors in Elders with Dementia Living in Residential Care

Objectives: There exists little information describing the spectrum and correlations of sexual behaviors manifested by elders with dementia living in residential care. Methods: Data are from a retrospective case-control study of improper sexual behaviors manifested by 165 elders with dementia living in a residential care facility in 2005. Results: Three types of behavior were evident: (1) intimacy-seeking, (2) disinhibited, and (3) nonsexual. Intimacy-seeking behaviors were associated with Alzheimer disease, and disinhibited behaviors with non-Alzheimer dementias. Behavior type was associated with dementia severity. Conclusions: Delineation of the types of improper sexual behaviors occurring in dementia has practical implications for practice and research. Progress will require prospective studies with systematic ascertainment of cases and variables, and recruitment from large sampling frames.

The physical environment influences neuropsychiatric symptoms and other outcomes in assisted living residents

Although the number of elderly residents living in assisted living (AL) facilities is rising, few studies have examined the AL physical environment and its impact on resident well‐being. We sought to quantify the relationship of AL physical environment with resident outcomes including neuropsychiatric symptoms (NPS), quality of life (QOL), and fall risk, and to compare the effects for demented and non‐demented residents.

Personality disorder traits as predictors of subsequent first-onset panic disorder or agoraphobia

Determining how personality disorder traits and panic disorder and/or agoraphobia relate longitudinally is an important step in developing a comprehensive understanding of the etiology of panic/agoraphobia. In 1981, a probabilistic sample of adult (> or =18 years old) residents of east Baltimore were assessed for Axis I symptoms and disorders using the Diagnostic Interview Schedule (DIS); psychiatrists reevaluated a subsample of these participants and made Axis I diagnoses, as well as ratings of individual Diagnostic and Statistical Manual of Mental Disorders, Third Edition personality disorder traits. Of the participants psychiatrists examined in 1981, 432 were assessed again in 1993 to 1996 using the DIS. Excluding participants who had baseline panic attacks or panic-like spells from the risk groups, baseline timidity (avoidant, dependent, and related traits) predicted first-onset DIS panic disorder or agoraphobia over the follow-up period. These results suggest that avoidant and dependent personality traits are predisposing factors, or at least markers of risk, for panic disorder and agoraphobia-not simply epiphenomena.

The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations.

BACKGROUND Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimers Research and Treatment - Alzheimers Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described. OBJECTIVE To develop an instrument based on ISTAART-AA MBI criteria. METHODS Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults. RESULTS We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician. CONCLUSION The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.

Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are the main syndromes of the chromosome 9 ORF72 (C9ORF72) hexanucleotide repeat expansion, but studies have shown a substantial phenotypic diversity that includes psychiatric presentations. This study describes hippocampal sclerosis dementia (HSD) in carriers of the C9ORF72 mutation. We compared clinical and neuropathological features of HSD in carriers and noncarriers autopsied at Johns Hopkins. Carriers presented with amnesia, agitation, dissocial behavior, and impaired self-care, whereas noncarriers showed little agitation. The groups were not dissimilar in cognitive or motor dysfunction. Neuropathological examination of carriers showed cerebellar neuronal inclusions positive for ubiquitin, p62, and ubiquilin-2, and negative for TAR DNA-binding protein 43. Noncarriers did not have cerebellar inclusions. C9ORF72 repeat-associated non-ATG translation was confirmed by immunohistochemistry. These observations broaden the C9ORF72 phenotype and place HSD in the FTD spectrum. The amnesic phenotype of HSD, which is consistent with the focal hippocampal atrophy, should be included in clinical categorizations of FTD.

The Spectrum of Medical Illness and Medication Use Among Residents of Assisted Living Facilities in Central Maryland

BACKGROUND Although increasing numbers of older adults are living in assisted living facilities, there is little information on the types and amount of chronic medical illness and the medications required by such residents. To better inform efforts to optimize care in this setting, we sought to quantify chronic medical illnesses and their treatment. METHODS Medical diagnoses and treatments were derived from chart reviews and interviews of 198 residents of 22 randomly selected assisted living facilities (AL) in central Maryland. To evaluate the burden of medical illnesses, chronic conditions were categorized and quantified according to general (organ system) diseases, as well as 7 specific long-term care Clinical Practice Guidelines (CPG). Using logistic regression, we calculated the associations between facility-level characteristics and those residents with a) conditions from 3 or more general disease categories and, b) 2 or more CPG conditions. To evaluate medical treatment complexity, we categorized oral and certain non-oral medications, as well medications that typically require additional monitoring. RESULTS Almost one-half (46%) of AL residents had chronic conditions in 3 or more different general disease categories and one-fourth (25.2%) had 2 or more specific Clinical Practice Guideline (CPG) conditions. Residents with chronic conditions in 3 or more different general disease groups were more likely to live in larger facilities; otherwise, no other facility-level characteristics that we assessed were associated with residents having conditions from 3 or more general disease categories or 2 or more CPG conditions. One-half of all residents were taking medications that typically require additional monitoring and 25% of residents were receiving treatments of respiratory inhalers, eye drops and/or injections. CONCLUSIONS Many AL residents have multiple medical illnesses of different types and complexity. Given the increasing role of AL providers in the management of such conditions, appropriate adjustments in care provision will be needed for facilities to meet the needs of these residents.