Judith Neugroschl

Current Treatment and Recent Clinical Research in Alzheimer's Disease

The transition from either epidemiological observation or the bench to rigorously tested clinical trials in patients with Alzheimers disease is crucial in understanding which treatments are beneficial to patients. The amyloid hypothesis has undergone scrutiny recently, as many trials aimed at reducing amyloid and plaque have been completed or are in the testing phase. Examples include modulation of the secretases involved in beta amyloid formation, anti-aggregation agents, and immunotherapeutic trials. Other therapies targeting hyperphosphorylated tau and novel targets such as enhancement of mitochondrial function, serotonin receptors, receptor for advanced glycation end products, and nerve growth factor, as well as other strategies, are discussed. A brief review of the current Food and Drug Administration-approved treatments is included.

The Caregiver Activity Survey (CAS) : Longitudinal validation of an instrument that measures time spent caregiving for individuals with Alzheimer's disease

Family members incur substantial financial costs during the course of caring for an individual with Alzheimers disease. Much of this cost is associated with time spent in caregiving tasks, including supervision and communication with the patient, and assisting with activities of daily living. We have previously reported on the cross sectional reliability and validity of a scale that measures time spent caregiving, the Caregiver Activity Survey (CAS). This study extends our results to a longitudinal study of the validity of the instrument. Forty‐four outpatients with Alzheimers disease who lived with a primary caregiver were followed over a period of 1 year 6 months. At six month intervals, the patients were administered the Mini Mental State Exam (MMSE), Alzheimers Disease Assessment Scale (ADAS), and the Physical Self Maintenance Scale (PSMS). Caregivers completed the CAS. Over time, the CAS correlated significantly with the MMSE (r=−0.58, p=0.000), ADAS cognitive subscale (r=0.56, p=0.000) and PSMS (r=0.49, p=0.000). As patients declined, caregivers spent less time communicating with and more time supervising the patient. Excluding the communication item, time spent caregiving increased significantly over time. This prospective study longitudinally validates the CAS with Alzheimers patients. Copyright

Alzheimer's disease: diagnosis and treatment across the spectrum of disease severity.

Alzheimers disease exists along a spectrum, from early memory changes to functional dependence and death. Using a case illustration, we review the evaluation and diagnosis of mild cognitive impairment and the diagnosis and management of Alzheimers disease at each stage, including the management of both cognitive and behavioral/psychiatric aspects of the disease and end-stage and end-of-life care.

Biological Markers in Alzheimer Disease

Biological markers are important tools in identifying predisposing factors to disease, as diagnostic tests, and in monitoring disease progression. Alzheimer disease is believed to have a long preclinical phase, followed by mild cognitive impairment, and, finally, dementia. Detecting alterable predisposing factors or identifying patients in preclinical or early-stage illness offers the greatest potential to modifying disease course. The authors focus on: 1) predisposing factors, such as genetic risk factors and homocysteine; 2) laboratory markers, such as amyloid beta and tau protein; and 3) diagnostic markers, such as structural and functional neuroimaging. Many markers have been tested but have not been confirmed in subsequent studies. Other tests require complex and expensive laboratory evaluation or expertise, thereby limiting their use at present. Still others are markers only useful in later-stage illness. Nonetheless, the search for markers has increased our understanding of the biology of illness and has led to exciting new directions, with diagnostic as well as treatment implications.

Alcohol use disorders in geriatrics.

Alcohol use disorders cause significant morbidity and mortality in the geriatric population. This review article begins with a hypothetical case for illustration, asking what the primary care physician could do for a geriatric patient with alcohol abuse over a course of four office visits. Various aspects of alcohol use disorders in the geriatric population are reviewed, such as range of alcohol use, epidemiology, medical/psychiatric impact, detection, comprehensive treatment planning, modalities of psychotherapy, medication management, and resources for clinicians/patients.

The Utility of the Cognitive Function Instrument (CFI) to Detect Cognitive Decline in Non-Demented Older Adults

BACKGROUND Subjective cognitive complaint is a sensitive marker of decline. OBJECTIVE This study aimed to (1) examine reliability of subjective cognitive complaint using the Cognitive Function Instrument (CFI), and (2) assess the utility of the CFI to detect cognitive decline in non-demented elders. METHODS Data from a four-year longitudinal study at multiple Alzheimers Disease Cooperative Study (ADCS) sites were extracted (n = 644). Of these, 497 had Clinical Dementia Rating (CDR) global scores of 0 and 147 had a CDR of 0.5. Mean age and education were 79.5±3.6 and 15.0±3.1 years, respectively. All participants and their study partners completed the subject and study partner CFI yearly. Modified Mini-Mental State Exam (mMMSE) and Free and Cued Selective Reminding Test (FCSRT) were administered. Scores below the predetermined cut-off scores on either measure at annual visit were triggers for a full diagnostic evaluation. Cognitive decline was defined by the absence/presence of the trigger. RESULTS Three-month test retest reliability showed that inter-class coefficients for subject and study partner CFI were 0.76 and 0.78, respectively. Generalized estimating equation method revealed that both subject and study partner CFI change scores and scores from previous year were sensitive to cognitive decline in the CDR 0 group (p < 0.05). In the CDR 0.5 group, only the study partner CFI change score predicted cognitive decline (p < 0.05). CONCLUSION Cognitive decline was predicted differentially by CDR level with subject CFI scores providing the best prediction for those with CDR 0 while study partner CFI predicted best for those at CDR 0.5.

Attitudes and Perceptions of Research in Aging and Dementia in an Urban Minority Population

In dementia trials, minority participation is low. We assessed attitudes toward research in a community based urban poor minority sample of elderly adults attending senior center talks using the 7-item Research Attitudes Questionnaire (RAQ). Presentations on cognitive aging were given at senior centers, and 123 attendees completed the RAQ-7. On trust and safety questions, a significant minority (42-48%) responded neutrally or negatively. Encouragingly, on questions concerning the importance of research, 72-81% answered positively. More work can be done to capitalize on these findings to engage and foster trust, and this can be a focus of outreach.

Detection of mild cognitive impairment and early stage dementia with an audio-recorded cognitive scale.

BACKGROUND Physicians often miss diagnosis of mild cognitive impairment (MCI) or early dementia and screening measures can be insensitive to very mild impairments. Other cognitive assessments may take too much time or be frustrating to seniors. This study examined the ability of an audio-recorded scale, developed in Australia, to detect MCI or mild Alzheimers disease (AD) and compared cognitive domain-specific performance on the audio-recorded scale to in-person battery and common cognitive screens. METHOD Seventy-six patients from the Mount Sinai Alzheimers Disease Research Center were recruited. Patients were aged 75 years or older, with clinical diagnosis of AD or MCI (n = 51) or normal control (n = 25). Participants underwent in-person neuropsychological testing followed by testing with the audio-recorded cognitive screen (ARCS). RESULTS ARCS provided better discrimination between normal and impaired elderly individuals than either the Mini-Mental State Examination or the clock drawing test. The in-person battery and ARCS analogous variables were significantly correlated, most in the 0.4 to 0.7 range, including verbal memory, executive function/attention, naming, and verbal fluency. The area under the curve generated from the receiver operating characteristic curves indicated high and equivalent discrimination for ARCS and the in-person battery (0.972 vs. 0.988; p = 0.23). CONCLUSION The ARCS demonstrated better discrimination between normal controls and those with mild deficits than typical screening measures. Performance on cognitive domains within the ARCS was well correlated with the in-person battery. Completion of the ARCS was accomplished despite mild difficulty hearing the instructions even in very elderly participants, indicating that it may be a useful measure in primary care settings.

RESEARCH SATISFACTION IN ALZHEIMER’S TRIALS AND STUDIES AMONG PARTICIPANTS AND STUDY PARTNERS

BMI -0.324 0.057 0.630 0.073 24.80 3.88 28.97 3.73 12.57 <0.001 CIMT -0.194 0.051 0.216 0.082 0.70 0.07 0.74 0.10 5.250 <0.001 LDL-C -0.240 0.064 0.323 0.069 121.89 28.91 138.35 28.23 6.620 <0.001 HDL-C 0.498 0.055 -0.779 0.065 74.13 15.20 51.22 9.80 -21.751 <0.001 Triglycerides -0.510 0.051 0.755 0.086 66.73 25.74 129.26 60.24 14.402 <0.001 FSG -0.188 0.049 0.361 0.083 87.31 8.46 92.73 9.78 6.718 <0.001 FPS -0.564 0.059 0.857 0.063 2.16 2.25 6.89 2.14 25.926 <0.001 Latent Prevalence (Marginal Probability) 62% 38%

Recruiting US Chinese Elders Into Clinical Research for Dementia.

Purpose:This study described and evaluated the rapid recruitment of elderly Chinese into clinical research at the Mount Sinai Alzheimer’s Disease Research Center (MSADRC). Design and Methods:Methods of publicizing the study included lectures to local senior centers/churches and publications in local Chinese newspapers. The amount of time and success of these methods were evaluated. A “go to them” model of evaluation was used to enable participants to complete the study visit at locations where they were comfortable. Results:From January to December 2015, we recruited 98 participants aged 65 years or older who primarily speak Mandarin/Cantonese and reside in New York. The mean age and years of education was 73.93±6.34 and 12.79±4.58, respectively. The majority of participants were female (65.3%) and primarily Mandarin speaking (53.1%). Of all enrollees, 54.1% were recruited from community lectures, 29.6% through newspapers, 10.2% through word of mouth, and 6.1% from our clinical services. About 40.8% of participants underwent evaluations at the MSADRC, 44.9% at local senior centers/churches, and 14.3% at home. Implications:Given that the majority of our participants had low English proficiency, the use of bilingual recruiters probably allowed us to overcome the language barrier, facilitating recruitment. Our “go to them” model of evaluation is another important factor contributing to our successful recruitment.