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Coupled with aging, chronic stress experienced by dementia caregivers often leads to deteriorating health. Comparing caregivers and non-caregivers, we tested whether depression and loneliness mediate the relationship between caregiver status and a measure of chronic stress, the Perceived Stress Scale. Seventy-six cognitively normal older adults (mean age 72.7) were identified as caregivers or non-caregivers based on the functional independence of a paired family member. Caregivers reported more perceived stress, depression, and loneliness than non-caregivers. Using multiple mediation analyses, we found that loneliness and depression mediated the relationship of caregiver status with perceived stress. The loneliness effect on perceived stress was both direct and via its relationship with depressive symptoms. The findings suggest loneliness as a likely point of intervention to reduce caregiver stress. Initiatives to enable caregivers to maintain or develop social relationships apart from caregiver responsibilities may mitigate stress and its negative impact on mental and physical health.

Introduction: The impact of Alzheimer's disease (AD) on cognitive decline differs by sex. Composite scores are useful as singular outcomes in clinical trials, yet to date these have not been developed to measure sex-specific change., Method: We derived optimal composites from component scales available in the AD Neuroimaging Initiative (ADNI) database among cognitively normal and mild cognitively impaired subjects who are cerebrospinal fluid amyloid-β positive for early AD. Maximally sensitive composites were constructed separately for men and women using standard formulas. We compared the statistical power of the composites with the ADNI Prodromal Alzheimer's Cognitive Composite., Results: Among 9 cognitive measures and clinical dementia rating sum of boxes, the optimal sex-specific composites included 5 measures, including the clinical dementia rating and 4 distinct cognitive measures. The sex-specific composites consistently outperformed sex-agnostic composites and the ADNI Prodromal Alzheimer's Cognitive Composite., Discussion: Sex-specific composite scales may improve the power of longitudinal studies of early AD and clinical trials., (© 2019 The Authors.)

Background: PSP, like Alzheimer's disease (AD), is a tauopathy. The etiopathogenesis of PSP is not well known and the role of stress has not yet been examined. Recent studies have shown that stress increases the risk for developing AD. This study investigates the role of stress as a risk factor for PSP., Objective: B To examine the association between the development of progressive supranuclear palsy (PSP) and self-reported life stressors., Methods: 76 patients diagnosed with PSP according to the NINDS-SPSP criteria and 68 age-matched unrelated controls were administered a life stressor questionnaire. Stress was quantified as total number of events, number of life changing events, and number of events characterized by self-rated severity. Conditional odds ratio (OR) was calculated for each measure, with participants in the highest quartile of each measure being defined as high-exposure in relation to all other participants., Results: There were no significant differences between the reported number of total events or life-changing events in cases and controls. However, we found 24.4% of cases (N = 11) and 9.1% of controls (N = 5) had a higher exposure to high severity events, yielding an OR of 3.2 (p = 0.04)., Conclusions: We found that cases have over a three times greater odds of high exposure to high-severity events than controls prior to the clinical development of PSP, while there were no differences in overall number of reported events. Our findings suggest that high exposure to highly stressful events may be associated with the development of PSP.

Importance: Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials., Objective: To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS)., Design, Setting, and Participants: A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013., Exposure: Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion., Main Outcomes and Measures: Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years., Results: Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P < .001 for all); behavioral domain scores did not diverge significantly between groups., Conclusions and Relevance: Using these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.

Psychological and psychosocial resources, including resilience and social support, have traditionally been studied in the context of the stress paradigm and, more recently, in the context of successful aging. This study used moderated mediation analyses to examine the role of perceived stress in the relationships between physical and mental health functioning and self-rated successful aging (SRSA) and whether differences between people in level of resilience and social support changes the role of perceived stress in these relationships. A cross-sectional study of 1,006 older adults (mean age: 77 years) completed scales addressing SRSA, physical and mental health functioning, perceived stress, resilience, and social support. Results indicated that the strength of relationships between both physical and mental health functioning and SRSA were reduced after accounting for variation in level of perceived stress. The role of perceived stress in the association between mental health functioning and SRSA was found to be stronger among participants with the highest levels of resilience, and the influence of perceived stress on the degree of relationship between physical health functioning and SRSA was stronger among those with greatest social support. These findings suggest that interventions to reduce perceived stress may help break the link between disability and poor well-being in older adults. The findings further suggest that the impact of such interventions might differ depending on psychological resources (i.e., resilience) for mental health disabilities and external resources (i.e., social support) for those with physical health problems. The complex interplay of these factors should be taken into account in clinical settings., (Copyright © 2015 American Association for Geriatric Psychiatry. All rights reserved.)

Initiation and inhibition of saccadic eye movements has been shown to be impaired in patients with Huntington's disease (HD) and premanifest gene carriers (PMGC), and may provide biomarkers useful in tracking phenotypic change. Computerized behavioral tests of prosaccade latency and disinhibition presented to 31 non-gene carriers (NGC), 25 PMGC, and 12 HD patients. These tests provided quantitative performance measures without use of eye-tracking equipment. Significant differences on saccade tests were found, with PMGC intermediate between NGC and HD patients. Saccade latency discriminated PMGC from NGC, whereas saccade disinhibition discriminated PMGC from HD patients. Results suggest utility of behavioral saccade measures as premanifest indicators of phenoconversion in HD.

The goal of this study was to explore whether the Montreal Cognitive Assessment (MoCA), a new screening instrument, would be more sensitive to mild to moderate cognitive impairment in Huntington's disease (HD) than an established screening measure, the Mini Mental State Exam (MMSE). Our reasoning for this query is that the MoCA includes a broader range of test items and an additional assessment of executive functioning and attention compared with the MMSE. Using the receiver operating characteristic (ROC) analysis to examine performance of HD and control groups on both tests on overall scores and scores from various subdomains (i.e., visuospatial abilities) revealed that the MoCA achieved higher sensitivity without sacrificing specificity in many domains relative to the MMSE.

The current study examined temporal order memory in preclinical Huntington's disease (pre-HD). Participants were separated into less than 5 years (pre-HD near) and more than 5 years (pre-HD far) from estimated age of clinical diagnosis. Participants completed a temporal order memory task on a computerized radial eight-arm maze. On the study phase of each trial, participants viewed a random sequence of circles appearing one at a time at the end of each arm. On the choice phase, participants viewed two circles at the end of the study phase arms and chose the circle occurring earliest in the sequence. The task involved manipulations of the temporal lag, defined as the number of arms occurring in the sample phase sequence between the two choice phase arms. Research suggests that there is more interference for temporally proximal stimuli relative to temporally distal stimuli. There were no significant differences between the pre-HD far group and controls on the temporal order memory task. The pre-HD near group demonstrated significant impairments relative to the other groups on closer temporal lags, but were normal on the furthest temporal lag. Therefore, temporal order memory declines with increased temporal interference in pre-HD close to estimated diagnosis of HD.

The present study compared the performance of individuals with Huntington's disease (HD) and Alzheimer's disease (AD) on three types of California Verbal Learning Test-Second Edition (CVLT-II) recognition discriminability indices (RDI): Source, Novel, and Total. The HD and AD groups did not differ significantly on Source RDI (all 16 targets versus the 16 previously presented, List B, distractors). However, HD patients performed significantly better than AD patients on Total RDI (all 16 targets versus all 32 distractors) and Novel RDI (all 16 targets versus 16 new distractors). Implications of these findings on the differentiation of the memory disorders associated with HD and AD are discussed.

Individuals in preclinical and clinical stages of Huntington's disease (HD) demonstrate impairments in olfactory functioning. In addition, HD patients are impaired in source memory for verbal stimuli. A task combining both source and odor memory may be particularly sensitive to early changes in HD. The present study examined source and item memory for olfactory and visual stimuli in 10 individuals with HD, 10 asymptomatic HD gene carriers, 8 nongene carriers who had a parent with HD, and 20 normal controls. During the study phase, a male and a female experimenter (sources) presented odors and objects to the participant in an alternating sequence. To assess item memory, a stimulus from the study phase (target) and a novel stimulus (distractor) were presented, and the participant was asked to choose the target. To assess source memory, the experimenter presented a stimulus and asked whether the male or female experimenter had previously presented the stimulus. Results indicate that source memory for both visual and olfactory stimuli was impaired in HD patients compared to normal controls. In asymptomatic gene carriers, however, source memory for olfactory stimuli, but not visual stimuli, was more impaired than in nongene carriers and normal controls. Furthermore, gene carriers and HD patients showed a similar degree of impairment in source memory for olfactory stimuli. The only significant impairment found in item memory was for olfactory stimuli in HD patients. These results suggest that source memory for olfactory stimuli may be particularly sensitive to neuropathological changes in preclinical stages of HD.

Objective and Background: Previous studies have shown that patients with frontal-striatal dysfunction demonstrate improved performance on tests of recognition memory relative to free recall memory, suggesting deficits in retrieval processes. Not all studies, however, have indicated that all patients with frontal-striatal dysfunction display this profile. In this study, we examined the ubiquity of this "retrieval deficit" profile in a relatively large sample of patients with Parkinson disease (PD) or Huntington disease (HD)., Methods: Participants included 150 patients with PD and 65 patients with HD. Patients were classified as demonstrating a retrieval deficit or not based on a comparison of their standardized performances on the Recognition Discriminability and Long-Delay Free Recall indices from the California Verbal Learning Test., Results: Results indicated that 1) a retrieval deficit was more prevalent in patients with HD than PD, 2) this group difference emerged only in patients with at least a mild level of global cognitive impairment, and 3) even when the profile did emerge more frequently in patients with HD, it was present in only 44% of the patients., Conclusions: These findings suggest that not all patient groups with frontal-striatal dysfunction display a retrieval deficit profile, but in groups that do (ie, patients with HD), it is more likely to appear in individuals with greater cognitive impairment.

Memory tests that are in a recall format have almost universally measured accuracy in terms of the number of target items reported by the examinee. However, this traditional scoring method can, in certain cases, result in artificially inflated memory accuracy scores. That is, just as a "yes" response bias and high false-positive rate on recognition testing can artificially inflate a patient's hit rate, so, too, a liberal response bias and high intrusion rate on recall testing can artificially inflate a patient's level of target recall. Recognition tests correct for this problem by using a discriminability measure that provides a single score of hit rate relative to false-positive rate; however, recall tests rarely provide a single score of recall accuracy that corrects for intrusion rate. In the present study, we examined the utility of a new recall discriminability measure that analyzes target recall relative to intrusion rate. Patients with Alzheimer's disease (AD) or Huntington's disease (HD) were administered the CVLT-II, which provides both the traditional measure of target recall and a new measure of recall discriminability. The results indicate that the new recall discriminability measure was superior to the traditional level of target recall measure in distinguishing the recall performance of AD and HD patients. Implications of these results for clinical practice and theories of memory disorder in dementia are discussed.

The influence of Huntington's disease (HD) on the olfactory event-related potential (OERP), an electrophysiological measure of olfactory information processing, has not been reported to date. In the present study, olfactory and auditory event-related potentials (ERPs) were recorded monopolarly from Fz, Cz, and Pz electrode sites in 8 patients with HD and 8 age- and gender-matched control participants. Results demonstrated that individuals with HD were delayed compared with controls on the P3 component of the OERP (p<.001), with a trend toward a significant delay on the auditory ERP P3 (p<.06). The effect size for OERP P3 latency (pi(2)=.72) was larger than that for the auditory P3 (pi(2)=.24), which has previously been shown to be delayed in HD. Patients performed significantly worse than controls did on all neuropsychological measures. These measures significantly correlated with several components of the OERP. These findings extend the understanding of olfactory deficits in HD., ((c) 2005 APA, all rights reserved.)

Background: Cross-sectional studies in Alzheimer's disease (AD) show a strong relationship between extrapyramidal motor signs and presence of psychosis, yet it remains unclear whether neuromotor abnormalities precede and therefore can predict development of psychosis in AD., Objective: To identify cognitive and motor risk factors for the development of psychosis in patients with AD., Methods: Baseline clinical motor ratings and instrumental measures of neuromuscular function were obtained from 54 nonpsychotic patients with AD who were evaluated annually for 2 years for the development of psychosis. Survival analyses were performed to identify incidence and risks associated with psychosis., Results: The incidence of new onset psychosis in our sample was 32.5% in 2 years. Patients with abnormal agonist muscle burst amplitudes during rapid alternating movements of the hand were more likely to develop psychosis than those without (OR = 4.31; p = 0.007). Women with AD also had a higher risk of developing psychosis within 2 years than men (OR = 1.33; p = 0.01)., Conclusions: Using simple noninvasive instrumental procedures for assessing neuromotor function, it may be possible to identify an individual's level of risk for developing psychosis during the course of AD.

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.

A Phase I, double-blind, placebo-controlled, single-dose, escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics, Inc.) was conducted in healthy elderly volunteers. This trial was designed to evaluate single-dose safety, tolerability, and pharmacokinetics. Potential cognitive domains that might benefit from AIT-082 were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease (AD). Preclinical studies indicate that AIT-082 has memory-enhancing properties, stimulates neuritogenesis, and upregulates neurotrophic factors. Subjects received a single oral dose of AIT-082 or placebo on a weekly basis for 5 wk. All patients received a placebo dose at baseline. Six subjects received increasing doses of AIT-082 over the next 4 wk at doses of 0.6, 2.0, 6.0, and 20.0 mg of AIT-082 per kilogram of body weight. Two subjects received placebo throughout the trial. Nine subjects were recruited. One subject was withdrawn after the third treatment visit owing to poor venous access. There were no serious adverse events. The drug was well-tolerated. The time to peak drug concentration was approx 85 min with an elimination half-life of approx 17.6 h. Performance on the Number Comparison, Symbol Digit, and Trails A tests improved with AIT-082 dosing compared to baseline (placebo). In conclusion, AIT-082 was rapidly absorbed by the oral route with a half-life suitable for once daily dosing. No problems with tolerability or safety were demonstrated.

Objective: To evaluate whether the relationship between extrapyramidal signs (EPS) and cognitive disturbances in Alzheimer's disease (AD) is influenced by illness duration., Methods: A multivariate regression analysis was used to study the relationships between EPS, illness duration and five cognitive ability areas based on the Mattis Dementia Rating Scale (DRS) in 89 clinically diagnosed AD patients with extrapyramidal motor involvement., Results: Severity of EPS was statistically associated with performance on four cognitive ability areas from the DRS including: attention, initiation and perseveration, construction and memory. Age was a significant factor related to severity of EPS. However illness duration did not contribute to the strength of the association between EPS and cognitive disturbances in patients with AD., Conclusions: The findings of the present study support the notion that while neuropsychological and motor functions often coexist in patients with AD, their relationship seems to be unrelated to degenerative processes that accumulate throughout the illness., (Copyright 2001 John Wiley & Sons, Ltd.)

Successful efforts to prevent health-care acquired infections occur daily in U.S. hospitals. However, few of these "success stories" are presented in the medical literature or discussed at professional meetings. Key components of successful prevention efforts include multidisciplinary teams, appropriate educational interventions, and data dissemination to clinical staff.

We describe the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance system. Elements of the system critical for successful reduction of nosocomial infection rates include voluntary participation and confidentiality; standard definitions and protocols; identification of populations at high risk; site-specific, risk- adjusted infection rates comparable across institutions; adequate numbers of trained infection control professionals; dissemination of data to health-care providers; and a link between monitored rates and prevention efforts.

Neurobehavioral disturbances often coexist with extrapyramidal signs (EPS) in patients with Alzheimer's disease (AD). In the present study, we examined the relationships between delusions and hallucinations and EPS by using standard observer ratings and sensitive electromyographic (EMG) measures in 52 patients with probable AD. On the basis of observer ratings, 36.5% of the patients exhibited psychotic features and 63.5% exhibited parkinsonism. Severity of clinically rated parkinsonism and the EMG measure of bradykinesia were significantly correlated with severity of neurobehavioral disturbances in this sample. The association between parkinsonism and delusions and hallucinations suggests a subcortical mechanism in the etiopathology of psychosis in AD.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, & Price, 1986).

HIV infection has been associated with decline in a number of cognitive functions that are components of 'working memory'. Thus, tests of working memory that require the interaction of these components may be particularly sensitive to cognitive dysfunction that arises from HIV infection. To assess this possibility, working memory was examined in 147 HIV-seropositive (HIV+) and 38 HIV-seronegative (HIV-) males using the Reading Span Test and the Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R). Speed of information processing, a component of some working memory tasks, was assessed with a version of the Sternberg Memory Scanning task. Results indicated that symptomatic HIV+ subjects were impaired relative to HIV- control subjects on the Reading Span and Digit Span tests. Asymptomatic and mildly symptomatic HIV+ groups exhibited a trend toward impairment on these tests, and on the whole, a greater proportion of HIV+ subjects than HIV- subjects were impaired. The groups did not differ significantly in information processing speed. These results indicate that deficits in working memory are apparent in at least a subset of HIV-infected individuals. These deficits are most apparent in symptomatic HIV+ individuals, but the decline may begin during the asymptomatic phase of infection.

In the present study, the California Verbal Learning Test (CVLT) was administered to symptomatic HIV+ (n = 31), asymptomatic HIV+ (n = 94), and HIV-normal control (HIV-NC) (n = 40) subjects to assess the prevalence and nature of their verbal memory deficits. Symptomatic HIV+ subjects were significantly impaired relative to HIV-control subjects on CVLT measures of acquisition and retention, and were significantly less likely than control subjects to use a semantic clustering strategy to support recall. The performance of the asymptomatic HIV+ subjects fell between those of the symptomatic HIV+ subjects and HIV-controls on almost every CVLT measure. A linear discriminant function analysis (DFA) was used to compare the performances of these three groups to Alzheimer's disease (AD). Huntington's disease (HD), and normal control (NC) subjects on three CVLT measures, including total recall over five learning trials, intrusion errors, and a derived score of delayed recognition discriminability minus the final learning trial. Significant differences were found between the number of symptomatic HIV+ subjects classified as HD (32%), AD (3%), and normal (65%), the number of asymptomatic HIV+ subjects classified as HD (16%), AD (1%), and normal (83%), and the number of HIV-NC subjects classified as HD (2%), AD (0%), and normal (98%). The profile of verbal memory deficits exhibited by the subgroup of impaired HIV+ subjects was similar to that of patients with HD, a prototypical subcortical dementia, and different from that of patients with AD, a prototypical cortical dementia. This finding is consistent with reports of the predominance of subcortical neuropathological changes associated with HIV infection.