Distinguishing Alzheimer's Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis.

It is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer's disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an added benefit of such platforms. This study utilizes a simplified and novel serum profiling platform, using mass spectrometry (MS), to help distinguish AD patient groups (mild and moderate) and controls, as well as to aid in understanding of biochemical phenotypes and possible disease development. A comparison of discriminating sera mass peaks between AD patients and control individuals was performed using leave one [serum sample] out cross validation (LOOCV) combined with a novel peak classification valuation (PCV) procedure. LOOCV/PCV was able to distinguish significant sera mass peak differences between a group of mild AD patients and control individuals with a p value of 10-13. This value became non-significant (p = 0.09) when the same sera samples were randomly allocated between the two groups and reanalyzed by LOOCV/PCV. This is indicative of physiological group differences in the original true-pathology binary group comparison. Similarities and differences between AD patients and traumatic brain injury (TBI) patients were also discernable using this novel LOOCV/PCV platform. MS/MS peptide analysis was performed on serum mass peaks comparing mild AD patients with control individuals. Bioinformatics analysis suggested that cell pathways/biochemical phenotypes affected in AD include those involving neuronal cell death, vasculature, neurogenesis, and AD/dementia/amyloidosis. Inflammation, autoimmunity, autophagy, and blood-brain barrier pathways also appear to be relevant to AD. An impaired VWF/ADAMTS13 vasculature axis with connections to F8 (factor VIII) and LRP1 and NOTCH1 was indicated and is proposed to be important in AD development.

Pharmacological Management of Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease (PD). The median age of onset for DLB (76.3 years) is younger than that seen in PD dementia (81.4 years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer's changes in their brains, explaining the wide variability in this disease's clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent (E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.

Sleep-Disordered Breathing and Cerebral Oxygenation During Sleep in Adults With Mild Cognitive Impairment.

The current study examined relationships between laterality in cerebral oxygenation (L-COX), sleep-disordered breathing (SDB), and daytime function in 16 adults with mild cognitive impairment (MCI). All participants underwent two nights of diagnostic polysomnography. Using dual-cerebral oximetry, L-COX was defined by differences ≥4% in right- versus left-sided percent cerebral oxyhemoglobin saturation. Eight patients had SDB. L-COX was found in five patients, but only on nights with SDB. Greater L-COX was associated more severe SDB: higher frequency of apneas + hypopneas per hour (r = 0.66, p < 0.01), desaturations per hour (r = 0.73, p < 0.01), and percent time with oxygen saturation <88% (r = 0.65, p < 0.01). Greater laterality, but not severity of SDB, was associated with poorer functional ability (Lawton Instrumental Activities of Daily Living Scale: r = -0.83, p = 0.02), lower cognitive function (Mini-Mental State Examination: r = -0.76, p = 0.03), and greater daytime sleepiness (Epworth Sleepiness Scale: r = 0.85, p < 0.001). L-COX associated with SDB suggests disruptions in cerebral autoregulation and need for aggressive treatment of SDB in individuals with MCI. [Res Gerontol Nurs. 2018; 11(6):282-292.].

Memory loss: Five new things.

PURPOSE OF REVIEW: Memory loss can be due to a wide variety of causes. We provide new information about the biology of common genetic and acquired causes of memory loss in older adults. RECENT FINDINGS: New data are available about the genetics of Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia. Amyloid PET, FDG-PET, and MRI have improved our understanding of how mild cognitive impairment evolves to AD. Several studies have shown links between concussion and chronic traumatic encephalopathy. Healthy eating and regular exercise have been demonstrated to slow cognitive decline in older adults. Randomized trials continue to show benefits for cholinesterase inhibitors and memantine in patients with AD and DLB. SUMMARY: New causes of memory loss are still being identified. More sophisticated diagnostic tools have improved our ability to make earlier diagnoses in older adults with memory loss.

Instrumental activities of daily living performance and role satisfaction in people with and without mild cognitive impairment: a pilot project.

OBJECTIVE: We investigated differences in observed performance of instrumental activities of daily living (IADLs) and self-reported satisfaction with social role performance between people with amnestic mild cognitive impairment (a-MCI) and age- and gender-matched control participants. METHOD: We measured observed performance of 14 IADLs using the Independence, Safety, and Adequacy domains of the Performance Assessment of Self-Care Skills (PASS) and the Patient-Reported Outcomes Measurement Information Systems (PROMIS) to examine satisfaction with social role performance. RESULTS: Total PASS scores were significantly lower in participants with a-MCI (median=40.6) than in control participants (median=44.2; p=.006). Adequacy scores were also significantly lower. No significant differences were found between groups on the PROMIS measures. CONCLUSION: IADL differences between groups were related more to errors in adequacy than to safety and independence. Occupational therapy practitioners can play a key role in the diagnosis and treatment of subtle IADL deficits in people with MCI.

Comment: Performance improvement with computer training in Parkinson disease.

Computer-based memory and attention training methods improve episodic recall in older adults who have amnestic mild cognitive impairment.(1,2) Memory and attention are highly interactive and interdependent processes due to their shared circuitry. The cognitive benefits of computer-based memory training appear to persist for at least 6 months.(1) Traditional cognitive training programs are administered by professionals and may cost as much as $15 to $100 an hour, depending on the educational level of the staff member who delivers the training.(2) More cost-effective methods of computer-based memory training are needed. In the study by Zimmermann et al.(3) on patients with Parkinson disease (PD), 2 types of computer training were compared: a specific cognitive training method (CogniPlus) and a nonspecific method, Nintendo Wii, a game console.

A program to improve detection of undiagnosed dementia in primary care and its association with healthcare utilization.

OBJECTIVE: Alzheimer's disease and related dementias are common and costly, with increased healthcare utilization for patients with these disorders. The current study describes a novel dementia detection program for veterans and examines whether program-eligible patients have higher healthcare utilization than age-matched comparison patients. DESIGN: Using a telephone-based case-finding approach, the detection program used risk factors available in the electronic medical record (EMR) and telephone-based brief cognitive screening. Holding illness severity constant, dementia detection and healthcare utilization were compared across age-matched groups with and without program risk factors. SETTING: Five Veterans Affairs Healthcare Network Upstate New York primary care clinics. PARTICIPANTS: Veterans aged 70 years and older. MEASUREMENTS: EMR data and the Charlson comorbidity index. RESULTS: Program-eligible patients (n = 5,333) demonstrated significantly greater levels of medical comorbidity relative to comparison patients and were on average more than twice as likely to be admitted to the hospital. They also had nearly double the number of outpatient visits to several services. Similar patterns were seen in those who screened positive on a brief cognitive measure, compared with those who screened negative. CONCLUSIONS: A novel program using EMR data to assist in the detection of newly diagnosed dementia in a clinical setting was found to be useful in identifying older veterans with multiple comorbid medical conditions and increased utilization of hospital and clinic services. Results suggest undetected cognitive impairment and dementia may significantly contribute to healthcare utilization and costs of care in older veterans.

Enhanced task-oriented training in a person with dementia with Lewy bodies.

Despite the inevitable loss of function seen in people with progressive dementias, interventions for reversing or minimizing functional loss are understudied. Research supports task-oriented training, but practical gaps in how to best evaluate clients for this training and how to implement it in clinical settings may be thwarting translation to occupational therapy practice. We structured an intervention model called STOMP (Skill-building through Task-Oriented Motor Practice) using a unique blend of task-oriented training and motor-learning principles. In this article, we describe through a case study the process and outcome of using STOMP to improve functional skills in a woman with moderate dementia with Lewy bodies. Our findings suggest that STOMP has the potential to serve as a structure for the evaluation and treatment of occupational performance deficits in people with dementia and that this model warrants further investigation.