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1.  Comparison of Two Informant Questionnaire Screening Tools for Dementia and Mild Cognitive Impairment: AD8 and IQCODE 
Dementia and mild cognitive impairment (MCI) are under-recognized in community settings. This may be due in part to the lack of brief dementia screening tools available to clinicians. We compared two brief, informant-based screening tests: the AD8 and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in a community-based neurology practice in the Midwestern United States
We examined 186 consecutive patients (44 controls, 13 with MCI, and 129 with dementia). Receiver operator characteristic curves were used to examine the ability of AD8 and IQCODE to discriminate between controls and MCI or dementia. Sensitivity, specificity, predictive values, and likelihood ratios were reported.
AD8 differentiated healthy controls from MCI (p<.001) or dementia (p<.001), as well as MCI from dementia (p=.008). The IQCODE differentiated controls and MCI from dementia (both p<.001), and between controls and MCI (p=.002). Both AD8 (AUC = 0.953, 95% CI: 0.92–0.99) and IQCODE (AUC = 0.930, 95% CI: 0.88–0.97) provided discrimination between controls and patients with dementia; however the AD8 had superior sensitivity detecting dementia (99.2%) and MCI (100%) compared to the IQCODE (79.1% for dementia, 46.1% for MCI) with non-overlapping confidence intervals. Using published cut-offs (AD8 ≥ 2, IQCODE ≥ 3.4), only one case of dementia was missed with the AD8 while the IQCODE failed to detect dementia in 27 individuals. The AD8 detected MCI in all 13 individuals while the IQCODE misclassified 7 individuals.
Both the AD8 and IQCODE were able to detect dementia in a community setting. The AD8, however, was more successful than IQCODE in detecting MCI. If simple and efficient screening for early cognitive impairment is the goal, particularly in the early stages (e.g., for prevention trials or public screening), the combination of an informant interview (the AD8) and a brief performance measure could be considered as they meet the basic requirements of the Personalized Prevention Plan for Medicare beneficiaries.
PMCID: PMC3981951  PMID: 24113559
Dementia; Screening; AD8; IQCODE; Mild Cognitive Impairment
2.  Collaborative transdisciplinary team approach for dementia care 
Alzheimer's disease (AD) has high economic impact and places significant burden on patients, caregivers, providers and healthcare delivery systems, fostering the need for an evaluation of alternative approaches to healthcare delivery for dementia. Collaborative care models are team-based, multicomponent interventions that provide a pragmatic strategy to deliver integrated healthcare to patients and families across a wide range of populations and clinical settings. Healthcare reform and national plans for AD goals to integrate quality care, health promotion and preventive services, and reduce the impact of disease on patients and families reinforcing the need for a system-level evaluation of how to best meet the needs of patients and families. We review collaborative care models for AD and offer evidence for improved patient- and family-centered outcomes, quality indicators of care and potential cost savings.
PMCID: PMC4308691  PMID: 25531688
Alzheimer's disease; caregiver-centered outcomes; collaborative care; dementia; models of care; neurocognitive disorders; patient-centered outcomes; transdisciplinary teams
3.  Internet-Based Dementia Resources: Physician Attitudes and Practices 
Despite the potential of the internet for informing clinical practice, little is know about physicians’ use of and attitudes about internet use for dementia care. We surveyed 373 physicians to inform development of on-line dementia education resources. Two thirds reported using internet-based resources in their clinical practices at least three times per week; 61% participated in on-line continuing medical education. Three fourths agreed that internet-based resources are helpful in clinical care but most expressed mixed views about quality of available information. Respondents reported limited awareness and use of dementia-specific internet resources, but expressed an interest in such information regarding screening, treatment, community resources, and patient education. National Institute on Aging-funded Alzheimer’s Disease Centers are in a unique position to disseminate on-line resources for physicians on dementia diagnosis, treatment, and care. Our study suggests that such a resource would be well received and utilized by physicians.
PMCID: PMC3137376  PMID: 21769164
Alzheimer’s disease; Internet; Medical Education
4.  Vocalization in Dementia: A Case Report and Review of the Literature 
Case Reports in Neurology  2014;6(1):126-133.
Vocalizations are part of the spectrum of the ‘negative’ behavioral and psychological symptoms of dementia (BPSD). We describe a patient with moderate-stage mixed dementia of Alzheimer's disease and cerebrovascular disease and a left orbitofrontal lesion exhibiting vocalization. The use of ‘redirection’ has been demonstrated to be an effective nonpharmacological means of controlling BPSD, while reducing caregiver distress.
Case Report
A 78-year-old right-handed African-American female presented with complaints of worsening memory and BPSD, causing significant caregiver distress. Throughout the evaluation, she constantly vocalized her son's name and made a continuous grunting noise, correlating with increased anxiety/agitation. We utilized a redirection technique, which achieved the immediate reduction of the vocalization symptoms. Caregiver psychoeducation was provided allowing them to use the redirection technique at home.
In patients with dementia exhibiting negative symptoms of BPSD, using nonpharmacologic techniques (i.e. redirection) may be indicated. Psychotropic medications rarely address negative BPSD symptoms, while simultaneously decreasing patient's quality of life. Nonpharmacologic approaches are beneficial as first-line therapy for negative BPSD.
PMCID: PMC4036439  PMID: 24926262
Alzheimer's disease; Dementia; Vocalization; Behavior and psychiatric symptoms of dementia; Nonpharmacologic interventions; Caregiver distress
5.  Capgras syndrome in Dementia with Lewy Bodies 
Capgras syndrome is characterized by the recurrent, transient belief that a person has been replaced by an identical imposter. We reviewed clinical characteristics of Dementia with Lewy Bodies (DLB) patients with Capgras syndrome compared to those without Capgras.
We identified 55 consecutive DLB patients (11 cases with Capgras syndrome (DLB-C) and 44 cases without evidence of Capgras (DLB). Semi-structured interviews with the patient and an informant, neurological exams, and neuropsychological testing were performed. Caregivers were assessed for caregiver burden and depression. Primary comparisons were made between DLB-C and DLB. Exploratory analyses using stepwise logistic regression and bootstrap analyses were performed to determine clinical features associated with Capgras.
DLB-C patients experienced more visual hallucinations and self-reported anxiety, had higher scores on the Neuropsychiatric Inventory, and were less likely to be treated with cholinesterase inhibitors at time of initial evaluation. Extrapyramidal symptoms and depression were not associated with Capgras. Caregivers of DLB-C patients had higher caregiver burden. DLB-C was associated with self-reported anxiety (OR 10.9; 95% CI 2.6-47.6). In a bootstrap analysis, clinical findings that were predictors of Capgras included visual hallucinations (log(OR) 18.3; 95% CI 17.9-19.3) and anxiety (log(OR) 2.9; 95% CI (0.31-20.2).
Our study suggests that Capgras syndrome is common in DLB and usually occurs in the presence of anxiety and visual hallucinations, suggesting related etiopathogenesis. Early appreciation of Capgras syndrome may afford the opportunity to alleviate caregiver burden and improve patient and caregiver outcomes.
PMCID: PMC4004517  PMID: 23211760
Lewy body; dementia; Capgras syndrome; caregiver burden; hallucinations; delusions
6.  Public–private partnerships improve health outcomes in individuals with early stage Alzheimer’s disease 
In a collaborative effort between the Missouri Department of Health, Area Agencies on Aging (AAA), Alzheimer Association, and academic researchers, we tested whether early dementia detection and comprehensive care consultations would improve health outcomes in care receivers (CRs) and their family caregivers (FCGs), therefore addressing an important public health concern.
Participants and methods
A total of 244 community-dwelling older adults screened for early-stage dementia by the AAA field staff were referred to the Alzheimer Association and participated in Project Learn MORE (Missouri Outreach and Referral Expanded) (PLM) – a 2-year, nonrandomized multisite intervention consisting of comprehensive care consultations to improve coping skills. PLM participants were compared against 96 controls receiving the Alzheimer Association’s “usual services” between January 2011 and December 2012. We examined CR and FCG outcomes, including burden, care confidence, and mood, as effects of PLM, on delaying transitions in level of care.
CRs showed improved knowledge (P=0.002) and reduced depression (P=0.007), while FCGs demonstrated improved knowledge (P=0.003) and ability to identify sources of support for the CR (P=0.032) and for themselves (P=0.043). However, FCGs were more burdened after PLM (P=0.02), due to increased awareness of Alzheimer’s disease. PLM delayed transitions in care (odds ratio [OR] 3.32, 95% confidence level [CI]: 1.25–8.83) with the number needed to treat =6.82.
PLM was successful in improving detection of incident cases of dementia in the community and in connecting patients and their families with needed services. Our findings support the use of state agencies and community service partners to detect dementia. Early implementation of psychosocial interventions could have significant impact in improving patient- and family-centered outcomes, potentially providing a cost-efficient alternative to pharmacotherapy.
PMCID: PMC3986334  PMID: 24748780
dementia screening; AD8; social support; caregiver burden; transition in care
7.  Lewy body dementia: the impact on patients and caregivers 
Lewy body dementia (LBD) is the second most common neurodegenerative dementia in older adults, yet there remains a delay in diagnosis that limits healthcare providers’ ability to maximize therapeutic outcomes and enhance patient and caregiver quality of life. The impact of LBD on patients includes limiting the potential exposure to medications that may cause adverse outcomes, and addressing how the disease manifestations, such as autonomic features and behavior, affect quality of life. LBD impact on caregivers has been discussed to a greater degree in the literature, and there is clear evidence of caregiver burden and grief associated with disease manifestations. Other common caregiving concerns, such as access to care, prevention of hospitalization, managing behavior, and reviewing prognosis and nursing home placement, are important to comprehensively address the needs of patients with LBD and their caregivers.
PMCID: PMC4054937  PMID: 25031635
8.  The spectrum of cognitive impairment in Lewy body diseases 
Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson’s disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. Cognitive dysfunction is now recognized to occur not only in more advanced Parkinson’s disease, but also in early, untreated patients, and even in those patients with pre-motor syndromes such as REM behavior disorder and hyposmia. In recent years, the concept of “mild cognitive impairment” as a transitional or pre-dementia state in Parkinson’s disease has emerged. While this has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson’s disease, it has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson’s disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. While these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other aspects such as timing of cognitive, behavioral, and motor symptoms, medication responses, and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point-counterpoint approaches.
PMCID: PMC4126402  PMID: 24757110
Cognition; Dementia; Executive function; Mild cognitive impairment; Parkinson’s disease
9.  Longitudinal Associations between Physical and Cognitive Performance among Community-Dwelling Older Adults 
PLoS ONE  2015;10(4):e0122878.
To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.
PMCID: PMC4395358  PMID: 25875165
10.  Sarcopenia and impairment in cognitive and physical performance 
Whether older adults with sarcopenia who underperform controls on tests of physical performance and cognition also have a higher likelihood of combined cognitive-physical impairment is not clear. We assessed the impact of sarcopenia on impairment in both aspects of functionality and the relative contribution of its components, muscle mass and strength.
Two hundred and twenty-three community-dwelling adults aged 40 years and older (mean age =68.1±10.6 years; 65% female) were recruited and underwent physical functionality, anthropometry, and cognitive testing. Participants with low muscle mass were categorized as pre-sarcopenic; those with low muscle mass and muscle strength as sarcopenic; those with higher muscle mass and low muscle strength only were categorized as non-sarcopenic and were compared on risk of cognitive impairment (Montreal Cognitive Assessment <26; Ascertaining Dementia 8 ≥2), physical impairment (Mini Physical Performance Test <12), both, or neither by ordinal logistic regression.
Compared to controls, those with sarcopenia were six times more likely to have combined cognitive impairment/physical impairment with a fully adjusted model showing a three-fold increased odds ratio. The results were consistent across different measures of global cognition (odds ratio =3.46, 95% confidence interval =1.07–11.45 for the Montreal Cognitive Assessment; odds ratio =3.61, 95% confidence interval =1.11–11.72 for Ascertaining Dementia 8). Pre-sarcopenic participants were not different from controls. The effect of sarcopenia on cognition is related to low muscle strength rather than low muscle mass.
Individuals with sarcopenia are not only more likely to have single but also to have dual impairment in cognitive and physical function. Interventions designed to prevent sarcopenia and improve muscle strength may help reduce the burden of cognitive and physical impairments of functionality in community-dwelling seniors.
PMCID: PMC4388078  PMID: 25878493
cross-sectional; muscle strength; muscle mass; physical impairment; cognitive impairment; older adults
11.  Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch 
OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer’s disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer’s disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch.
Using OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. ‘Improvers’ were patients who improved on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS-IADL). ‘Non-decliners’ were patients who did not decline on either scale.
Overall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were ‘improvers’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were ‘non-decliners’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48.
More patients with mild-to-moderate Alzheimer’s disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are ‘improvers’ or ‘non-decliners’ i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch.
Trial registration identifier: NCT00506415; registered July 20, 2007.
Electronic supplementary material
The online version of this article (doi:10.1186/s13195-014-0088-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4353453  PMID: 25755685
12.  Lewy Body Dementia: The Under-Recognized but Common FOE 
Editor’s note:
After Alzheimer’s disease, Lewy body dementia (LBD) is the most prevalent progressive dementia of the many cognitive disorders wreaking unspeakable havoc on millions of lives. LBD is characterized by the presence of Lewy bodies, which are abnormal aggregates of a protein called alpha-synuclein, and are found in regions of the brain that regulate behavior, memory, movement, and personality. Many of the symptoms of Alzheimer’s, Parkinson’s, and LBD overlap, but LBD is more difficult to diagnose. Underdiagnosis is just part of the reason why LBD is unknown to the public and many health-care providers, and why funding for research lags far behind that for almost every other cognitive disorder.
PMCID: PMC3999867  PMID: 24772233
13.  Capgras syndrome in Dementia with Lewy Bodies 
Capgras syndrome is characterized by the recurrent, transient belief that a person has been replaced by an identical imposter. We reviewed clinical characteristics of Dementia with Lewy Bodies (DLB) patients with Capgras syndrome compared to those without Capgras.
We identified 55 consecutive DLB patients (11 cases with Capgras syndrome (DLB-C) and 44 cases without evidence of Capgras (DLB). Semi-structured interviews with the patient and an informant, neurological exams, and neuropsychological testing were performed. Caregivers were assessed for caregiver burden and depression. Primary comparisons were made between DLB-C and DLB. Exploratory analyses using stepwise logistic regression and bootstrap analyses were performed to determine clinical features associated with Capgras.
DLB-C patients experienced more visual hallucinations and self-reported anxiety, had higher scores on the Neuropsychiatric Inventory, and were less likely to be treated with cholinesterase inhibitors at time of initial evaluation. Extrapyramidal symptoms and depression were not associated with Capgras. Caregivers of DLB-C patients had higher caregiver burden. DLB-C was associated with self-reported anxiety (OR 10.9; 95% CI 2.6–47.6). In a bootstrap analysis, clinical findings that were predictors of Capgras included visual hallucinations (log(OR) 18.3; 95% CI 17.9–19.3) and anxiety (log(OR) 2.9; 95% CI (0.31–20.2).
Our study suggests that Capgras syndrome is common in DLB and usually occurs in the presence of anxiety and visual hallucinations, suggesting related etiopathogenesis. Early appreciation of Capgras syndrome may afford the opportunity to alleviate caregiver burden and improve patient and caregiver outcomes.
PMCID: PMC3713629  PMID: 12489921
Lewy body; dementia; Capgras syndrome; caregiver burden; hallucinations; delusions
Alzheimer’s disease (AD) research faces challenges to successful enrollment, especially to clinical trials and biomarker studies. Failure to recruit the planned number of participants in a timely fashion threatens the internal validity and success of clinical research, raising concerns about external validity and generalizability of results, and possibly leading to disparities in disease treatment. Methods to improve recruitment exist, but require varying levels of staff effort and financial resources and evidence of effectiveness is often lacking or inconsistent. In this review, we summarize some of the available methods to improve AD research recruitment, the available literature to support or refute these strategies, and some of the experiences at the authors’ AD Research Centers. We discuss the use of community-based participatory research principles and participant registries as a means to enhance research enrollment and increase diversity of research samples.
PMCID: PMC3945167  PMID: 24322484
Alzheimer’s Disease; Recruitment; Registries; Clinical Trials; Community-Based Participatory Research; Research Participation
15.  Implementation of Geriatric Acute Care Best Practices:Initial Results of The NICHE SITE Self -Evaluation 
Nursing & health sciences  2013;15(4):518-524.
Nurses Improving Care of Healthsystem Elders (NICHE) provides hospitals with tools and resources to implement a geriatric initiative to improve health outcomes and experiences for older adults and their families. Beginning in 2011, members have engaged in a process of program self-evaluation, designed to evaluate internal progress toward developing, sustaining and disseminating NICHE. This manuscript describes the NICHE Site Self -evaluation and reports the inaugural self-evaluation data in 180 North American hospitals. NICHE members evaluate their program utilizing the following dimensions of a geriatric acute care program: guiding principles, organizational structures, leadership, geriatric staff competence, interdisciplinary resources and processes, patient- and family-centered approaches, environment of care, and quality metrics. The majority of NICHE sites were at the progressive implementation level (n= 100, 55.6%), having implemented interdisciplinary geriatric education and the geriatric resource nurse (GRN) model on at least one unit; 29% have implemented the GRN model on multiple units, including specialty areas. Bed size, teaching status, and Magnet® status were not associated with level of implementation, suggesting that NICHE implementation can be successful in a variety of settings and communities.
PMCID: PMC3949432  PMID: 23656606
acute care; models; older adults; program evaluation
Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer disease (AD). DLB is characterized pathologically by Lewy body and Lewy neuritic pathology, often with variable levels of Alzheimer-type pathology. Core clinical features include fluctuating cognition, visual hallucinations, and parkinsonism resulting in greater impairments of quality of life, more caregiver burden, and higher health-related costs compared with AD. These issues, together with a high sensitivity to adverse events with treatment with antipsychotic agents, make the need for an early and accurate diagnosis of DLB essential. Unfortunately, current consensus criteria are highly specific but lack sufficient sensitivity. Use of composite risk scores may improve accuracy of clinical diagnosis. Imaging findings, particularly targeting dopaminergic systems have shown promise as potential markers to differentiate DLB from AD. A combination of non-pharmacologic treatments and pharmacotherapy interventions may maximize cognitive function and overall quality of life in DLB patients.
PMCID: PMC4219734  PMID: 25379359
Dementia with Lewy bodies; Alzheimer’s disease; Parkinson’s disease; Lewy bodies; Risk Scores; Aging; Neuropathology; Neuroimaging; Biomarkers; Genetics; Therapeutics
17.  Reply: The impact of dementia prevalence on the utility of the AD8 
Brain  2011;135(1):e204.
PMCID: PMC3267977
Primary care providers routinely evaluate older adults and are thus in a position to first detect symptoms and signs of Alzheimer’s disease. In urban areas, diagnostic or management difficulties may be referred to specialists; however, in rural areas, specialists may not be available. The Clinician Partners Program (CPP) was initiated to enhance rural health providers’ ability in dementia diagnosis and care, and to increase research recruitment into dementia research studies of participants from rural communities.
The CPP is a 3-day “mini-residency” of didactic, observational and skill-based teaching techniques. Participants completed pre- and post-tests evaluating dementia knowledge, confidence in providing care, and practice behaviors.
Between 2000–2009, 146 healthcare professionals with a mean age of 45.7±10.8y attended the CPP; 79.2% were Caucasian, 58.2% were female, and 58% of participants had been in practice for more than 10y. Post-tests showed improvements in knowledge and confidence to diagnose and treat and increased use of dementia screening tools. Rural research participation in an urban Alzheimer Disease Research Center increased 52% over the pre-CPP period.
Primary goals were accomplished: increased knowledge and confidence, changed practice habits, and enhanced research recruitment. Educational programs such as the CPP may be beneficial for increasing access to accurate diagnoses and appropriate treatment of Alzheimer’s disease while also enhancing research participation.
PMCID: PMC3288449  PMID: 21399484
Alzheimer’s disease; physician education; research recruitment; dementia
19.  Current guidelines for dementia screening: shortcomings and recommended changes 
The availability of various guidelines regarding the diagnosis of Alzheimer’s disease (AD) leaves most primary care providers with the task of having to decide which guidelines to follow. This review will help them navigate these different guidelines and understand how they differ from previous guidelines. Challenges related to the use of these guidelines are discussed, including biomarker testing, the lack of recognition in the community of what constitutes memory impairment and how to best screen for it, and recommendations for easy and early detection and diagnosis in the clinical settings are made. Adoption of biomarkers in clinical practice will give primary care providers the means to establish with certainty the underlying pathology responsible for the observed clinical symptoms and increase their ability to establish the presence of AD pathology before symptoms occur and, therefore, potentially help prevent or slow down the progression to AD.
PMCID: PMC4140653  PMID: 25152772
Alzheimer’s disease (AD) is characterized by progressive declines in cognitive function and ability to carry out activities of daily living; and the emergence and worsening of behavioral/neuropsychiatric symptoms. While there is no cure for AD, non-pharmacologic interventions and medications that modulate neurotransmission can slow symptomatic progression. Medical foods may also be useful as adjuncts to pharmacologic agents in AD. Medium chain triglycerides aimed at improving cerebral metabolism significantly improve Alzheimer’s Disease Assessment Scale-Cognitive scores when added to ongoing pharmacotherapy in patients with mild-to-moderate AD. Combination of interventions, such as non-pharmacologic treatments, pharmacotherapy, and medical foods, with complementary mechanisms of action may provide a rational approach that may result in maximum preservation of cognitive function in patients with AD.
PMCID: PMC3437664  PMID: 22973426
biomarker; FDG-PET; ketone body; medical food
21.  Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle 
Subcortical circuits mediating sleep–wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine–Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep–wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep–wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders.
PMCID: PMC4160996  PMID: 25309500
hypersomnia; cognitive fluctuations; sleep; review; brain networks
22.  A review of interprofessional dissemination and education interventions for recognizing and managing dementia 
The number of individuals with dementia is expected to increase dramatically over the next 20 years. Given the complicated clinical, sociobehavioral, and caregiving skills that are needed to comprehensively assess and manage individuals with dementia, the gold standard of care requires involvement of an interprofessional team. This systematic review examined 4,023 abstracts, finding 18 papers from 16 studies where an interprofessional dissemination program was performed. Most studies found some improvement in clinician knowledge or confidence, or patient outcomes, though methods and patient and clinician populations were disparate. While a significant evidence base for assessing and managing individuals with dementia has been developed, few studies have examined how to disseminate this research, and even fewer in an interprofessional manner. These findings suggest that greater emphasis needs to be placed on disseminating existing evidence-based care and ensuring that programs are interprofessional in nature so that excellent, patient-centered care is provided.
PMCID: PMC4112072  PMID: 23879387
23.  Longitudinal Changes in Cognition in Parkinson's Disease with and without Dementia 
The longitudinal cognitive course in Parkinson's disease (PD) with and without dementia remains undefined. We compared cross-sectional models of cognition in PD (both with and without dementia), Alzheimer's disease (AD), and nondemented aging and followed the participants over time.
Previously validated models of cognitive performance in AD and nondemented aging were extended to individuals with PD (with dementia, n = 71; without dementia, n = 47). Confirmatory factor analysis and piecewise regression were used to compare the longitudinal course of participants with PD with 191 cognitively healthy subjects and 115 individuals with autopsy-confirmed AD.
A factor analytic model with one general factor and three specific factors (verbal memory, visuospatial memory, working memory) fit demented and nondemented PD. Longitudinal change indicated that individuals with PD with dementia declined significantly more rapidly on visuospatial and verbal memory tasks than AD alone. Cognitive declines across all factors in AD and PD dementia accelerated several years prior to clinical dementia diagnosis.
Both specific and global cognitive changes are witnessed in PD and AD. Longitudinal profiles of cognitive decline in PD and AD differed. PD with or without dementia has a core feature of longitudinal decline in visuospatial abilities.
PMCID: PMC3047760  PMID: 21242691
Alzheimer's disease; Parkinson's disease with dementia; Parkinson's disease/parkinsonism; Longitudinal cognitive course; Confirmatory factor analysis
24.  Mild Physical Impairment Predicts Future Diagnosis of Dementia of the Alzheimer Type 
Journal of the American Geriatrics Society  2013;61(7):10.1111/jgs.12255.
To determine whether mildly impaired physical function (based on performance-based assessment) is associated with the development of dementia of the Alzheimer type (DAT) in cognitively normal older adults.
Longitudinal, observational study with yearly assessments of physical and cognitive function. Mean follow-up was 5 years.
Knight Alzheimer’s Disease Research Center at Washington University, St. Louis, Missouri.
Four hundred thirty-five cognitively normal adults, age 60 years or older participating in longitudinal studies of aging.
Survival analyses were used to examine whether scores on the 9-item Physical Performance Test (PPT) predicted time to DAT diagnosis. Cox proportional hazards models were used to examine associations between the PPT total scores and time to cognitive impairment and DAT; as well as the association of time to these events while adjusting for, and simultaneously testing the effects of age, gender, education, and presence of at least one apolipoprotein (APOE) ε4 allele.
During the follow-up period, 81 participants developed DAT. Compared to those who remained cognitively normal, participants diagnosed with DAT were older (81 vs 74.2 years; p=.001) and had worse performance on the PPT (25.5 vs 28.1; p=.009). Time to DAT diagnosis was associated with total scores on the PPT (hazard ratio [HR] =.89, 95% CI=.86–.93, p<.001) such that time to a DAT diagnosis was slower for participants with higher physical performance scores. In the adjusted analysis, the PPT scores significantly predicted time to a DAT diagnosis (HR =.94, 95% CI=.89–.99, p<.022).
The presence of mild physical impairment in cognitively normal older adults is associated with subsequent development of DAT. Although the physical impairment may be sufficiently mild that it is recognized only with performance-based assessments, its presence may predate clinically detectable cognitive decline.
PMCID: PMC3809089  PMID: 23647233
Dementia of Alzheimer type; physical performance; predictors; frailty
Approximately 3.2 million hospital stays annually involve a person with dementia, leading to higher costs, longer lengths of stay and poorer outcomes. Older adults with dementia are vulnerable when hospitals are unable to meet their special needs.
We developed, implemented and evaluated a training program for 540 individuals at 4 community hospitals. Pre-test, post-test and a 120-day delayed post-test were collected to assess knowledge, confidence and practice parameters.
The mean age of the sample was 46y; 83% were Caucasian, 90% were female and 60% were nurses. Upon completion, there were significant gains (p’s <.001) in knowledge and confidence in recognizing, assessing and managing dementia. Attendees reported gains in communication skills and strategies to improve the hospital environment, patient safety and behavioral management. At 120 days, 3 of 4 hospitals demonstrated maintenance of confidence. In the hospital that demonstrated lower knowledge and confidence scores, the sample was older and had more nurses and more years in practice.
We demonstrate the feasibility of training hospital staff about dementia and its impact on patient outcomes. At baseline, there was low knowledge and confidence in the ability to care for dementia patients. Training had an immediate impact on knowledge, confidence and attitudes with lasting impact in 3 of 4 hospitals. We identified targets for intervention and the need for ongoing training and administrative reinforcement in order to sustain behavioral change. Community resources, such as local chapters of the Alzheimer’s Association, may be key community partners in improving care outcomes for hospitalized persons with dementia.
PMCID: PMC2955811  PMID: 20625267
Dementia; Hospital Care; Education

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