Biomedical subjects

Mary Sano

Publications and source records attributed to Mary Sano.

At least 19 recordsLinked to original sources

PubMed2024

X-chromosome-wide association study for Alzheimer's disease.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Humans↗

PubMed2006

Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression.

CONTEXT: The hallmark pathological changes in Alzheimer disease (AD) are abundant plaque and tangle formation, especially in the temporal lobes and hippocampus. Although there is increasing evidence that major depression may interact with neuropathological processes in AD, there have been no studies of neuropathological changes in AD as a function of history of major depression. OBJECTIVE: To test the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the hippocampus of patients with AD with a lifetime history of major depressive disorder, as compared with patients with AD without depression history. DESIGN: Postmortem study. SETTING: Nursing home. PARTICIPANTS: The brains of 52 patients with AD without a lifetime history of major depression were compared with the brains of 50 patients with AD with a lifetime history of major depression. MAIN OUTCOME MEASURES: Neuropathological ratings from the Consortium to Establish a Registry in Alzheimer Disease battery. RESULTS: Brains of patients with AD with a lifetime history of depression showed higher levels of both plaque (P<.005) and tangle (P<.002) formation within the hippocampus than brains of patients with AD without a history of depression. Post hoc analyses showed that patients with AD who had a history of depression exhibited more rapid cognitive decline than patients without a history of depression (P<.004). Furthermore, within the group of patients with AD with a history of depression, patients who exhibited concurrent depression at the time of first diagnosis of AD exhibited more pronounced neuropathological changes in the hippocampus (P<.006). CONCLUSIONS: In AD, the presence of a lifetime history of depression corresponds to increases in AD-related neuropathological changes within the hippocampus. These changes go along with more rapid cognitive decline in patients with AD with a history of depression, and are more pronounced in patients with AD suffering from depression early on in the disease process, suggesting an interaction between major depression and AD neuropathology.

Age Factors↗

PubMed2006

Clinical characteristics and longitudinal changes of informal cost of Alzheimer's disease in the community.

Most estimates of the cost of informal caregiving in patients with Alzheimer's disease (AD) remain cross-sectional. Longitudinal estimates of informal caregiving hours and costs are less frequent and are from assessments covering only short periods of time. The objectives of this study were to estimate long-term trajectories of the use and cost of informal caregiving for patients with AD and the effects of patient characteristics on the use and cost of informal caregiving. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States (n=170). Generalized linear mixed models were used to estimate the effects of patient characteristics on use and cost of informal caregiving. Patients' clinical characteristics included cognitive status (Mini-Mental State Examination), functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities, psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal signs. Results show that rates of informal care use and caregiving hours (and costs) increased substantially over time but were related differently to patients' characteristics. Use of informal care was significantly associated with worse cognition, worse function, and higher comorbidities. Conditional on receiving informal care, informal caregiving hours (and costs) were mainly associated with worse function. Each additional point on the BDRS increased informal caregiving costs 5.4%. Average annual informal cost was estimated at $25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4.

Aged↗

PubMed2006

Neuropsychological testing in the diagnosis of dementia.

Neuropsychological testing can play a major role in the diagnosis of dementia by documenting cognitive deficits, the key criteria for the diagnosis. Because the most common dementia diagnosis, Alzheimer's disease, focuses on memory impairment, tests to assess this domain and to detect and characterize memory deficit are well established with recognized predictive value. Other neuropsychological domains are less well characterized and there are fewer tools to assess them. One domain that has been characterized as important in a number of other dementias is executive function. Improved neuropsychological assessment and characterization of other domains, such as executive function and attention, may assist in better identifying the pathophysiology of deficits in these areas, perhaps in combination with new technologies such as functional imaging. Finally, improved assessment tools for specific cognitive domains should assist in identifying a broad range of cognitive deficits at earlier stages and ultimately lead to more effective interventions for a wider range of cognitive deficits.

Cognition↗

PubMed2006

Cardiac risk factors and potential treatments in Alzheimer's disease.

Dementia is one of the commonest neurological disorders in the elderly population. In regards to the increasing longevity of populations worldwide, prevention of dementia has become a major public health challenge. There has been an intense research in the identification of modifiable risk factors for dementia. These risk factors could then be used as targets for intervention, pharmacologic or non-pharmacologic. Numerous reports of the relation between cardiovascular risk factors and cognitive decline and dementia have been published over the past years. This review focuses on the cardiovascular risk factors hypertension, hyperlipidemia and diabetes mellitus as targets for prevention of cognitive decline, overall dementia and Alzheimer's disease. Observational studies and clinical trials regarding the association between antihypertensive, lipid lowering and antidiabetic medications and the risk of impaired cognition, dementia or Alzheimer's disease are reviewed. Based on these data, we propose that early interventions at reducing these cardiovascular risk factors may have an impact on future incidence and prevalence of cognitive deficits of many etiologies including Alzheimer's disease.

Alzheimer Disease↗

PubMed2006

Women's cognitive and affective health and neuropsychiatry.

Recent interest in women's health has focused on the cognitive consequences of aging and hormonal changes. Based on hypotheses about estrogenic effects in the central nervous system (CNS), large-scale clinical trials were designed to address the efficacy of hormone replacement on protection against dementia and cognitive decline. Surprisingly, an absence of risk reduction for dementia and cognitive loss was found and much reanalysis of these findings has focused on timing of hormone replacement. Here we take a broad perspective to address a fuller range of psychological health. Gender differences in other psychiatric conditions including depression and anxiety have been attributed to hormones, and the neurotransmitter systems that are implicated in affective disorders may have an impact on cognitive impairment as well. Hormonal influences on neurotrophic mechanisms, as well as neurotransmitter effects, may be responsible for a breadth of neuropsychiatric conditions, particularly in aging. This review will focus on cognition, mood and anxiety issues among women with an emphasis on changes associated with aging. We will review data on the epidemiology of these entities and examine the biological mechanisms, which may be involved, with an emphasis on those mechanisms that may contribute to the multiple aspects of neuropsychiatry and women's health.

Bipolar Disorder↗

PubMed2005

Vitamin E and donepezil for the treatment of mild cognitive impairment.

BACKGROUND: Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. METHODS: In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. RESULTS: A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. CONCLUSIONS: Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.

Alzheimer Disease↗

PubMed2005

Relationship of neuropsychological performance to functional status in nursing home residents and community-dwelling older adults.

OBJECTIVES: The authors examined the association between neuropsychological tests of executive functioning and episodic memory and functional disability in nursing home residents versus community-dwelling older adults. METHODS: The neuropsychological performance of 96 residents from the Jewish Home and Hospital, Bronx, NY and 192 gender- and age-matched older adults from residential communities in the New York metropolitan area was assessed in eight tasks (Word List Recall, Delayed Recall, Recognition, Boston Naming, Verbal Fluency, Trailmaking A and B, and Digit Symbol Substitution). Functional status was derived from the Clinical Dementia Rating scale (CDR) extended activities of daily living scores. Regression analyses were performed to test for differences in cross-sectional age-gradients for cognitive and functional status between nursing home residents and community-dwellers. Furthermore, regression analyses, controlling for age, gender, dementia status, and education, were performed to determine the association between neuropsychological performance and functional status, comparing domains of executive functioning and memory. RESULTS: Community-dwelling older adults showed age-related deficits both in overall cognitive status and functional disability, which were larger in nursing home residents. Executive functioning was associated with functional disability beyond the effects of age, gender, education, dementia status, residential status, overall cognitive status, memory, and cognitive speed. CONCLUSION: Executive functioning is associated with functional deficits in both community-dwelling older adults and nursing home residents. Measures of executive functioning may prove useful in intervention studies aimed at delaying institutionalization.

Aged↗

PubMed2005

Neuropsychological differences between late-onset and recurrent geriatric major depression.

OBJECTIVE: Executive dysfunction, possibly related to vascular pathology, has been well documented in patients with a first episode of major depressive disorder in later life (late-onset geriatric major depression). However, it is unclear whether the neuropsychological presentation differs in patients with a lifetime history of major depressive disorder (recurrent geriatric major depressive disorder). The purpose of this study was to explore differences in neuropsychological function, symptoms, and cardiovascular comorbidity between patients with late-onset and recurrent geriatric major depression. METHOD: The study used a two-by-two factorial design in which one factor was current major depressive disorder (present versus absent) and the second factor was lifetime history of depression (present versus absent). Neuropsychological measures of executive functioning and episodic memory, as well as psychopathological symptoms and comorbid medical illness, were examined in a total of 116 older adults. RESULTS: Patients with late-onset major depressive disorder showed specific deficits in attention and executive function, whereas patients with recurrent major depressive disorder exhibited deficits in episodic memory. The rates of anhedonia and comorbid cardiovascular illness were higher in patients with late-onset geriatric major depressive disorder. CONCLUSIONS: In contrast to recurrent geriatric major depressive disorder, late-onset major depressive disorder is characterized by specific deficits in tasks of attention and executive function, consistent with increased anhedonia and cardiovascular comorbidity. These findings, if confirmed, suggest that recurrent and late-onset geriatric major depressive disorder may represent distinct phenomenological entities. Such phenomenological differences as a function of lifetime history of major depression can guide research in the neurophysiology, prevention, and treatment of geriatric major depressive disorder.

Affective Symptoms↗

PubMed2004

Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials.

BACKGROUND: Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD. OBJECTIVE: To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial. DESIGN: Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial. SETTING: Memory disorder centers in the United States and Canada. PATIENTS: A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0. MAIN OUTCOME MEASURES: Clinical, neuropsychologic, functional, neuroimaging, and genetic measures. RESULTS: Mean +/- SD Alzheimer's Disease Assessment Scale-Cognitive Subscale scores were 5.6 +/- 3.3 for controls, 11.3 +/- 4.4 for patients with MCI, 18.0 +/- 6.2 for the AD CDR 0.5 group, and 25.2 +/- 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E epsilon4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD. CONCLUSIONS: Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.

Aged↗

PubMed2004

A guide to diagnosis of Alzheimer's disease.

A major challenge in the management of Alzheimer's disease (AD) is accurate diagnosis of the condition. Aging itself is associated with cognitive change, and physicians must first distinguish between age-associated complaints and true memory impairment as in AD before optimal management can begin. This article reviews tools used to assess and diagnose AD patients in both the primary care and clinical trial settings. AD assessment instruments commonly used in research may be too cumbersome for use in primary care. Tools specifically designed to meet the needs of busy practitioners that can accurately assess function, cognition, and global change will be reviewed. The issues of cognitive screening in old age and age-associated memory impairment will be discussed. Similarly, the pitfalls and advantages of routine cognitive screening in daily practice will be addressed.

Activities of Daily Living↗

PubMed2004

Economic effect of cholinesterase inhibitor therapy: implications for managed care.

The growing elderly population is at great risk for Alzheimer's disease (AD). In 1997, annual costs associated with AD were 100 billion dollars. Cholinesterase inhibitor (ChEI) therapy is most commonly used to manage patients with AD, but the economic implications arising from their use are not well known. A review of studies assessing the cost effectiveness of ChEIs suggests that ChEI therapy provides benefit at every stage of disease, with better outcomes resulting from persistent, uninterrupted treatment. The cost savings range from 73 dollars over two years to 3891 dollars over one year, depending on the type of study, drug evaluated, and economic model employed in the evaluation.

Aged↗

PubMed2003

Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial.

CONTEXT: Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. OBJECTIVE: To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. SETTING: Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. PARTICIPANTS: Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. INTERVENTIONS: Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. MAIN OUTCOME MEASURES: The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). RESULTS: The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. CONCLUSION: The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.

Activities of Daily Living↗

PubMed2003

Estrogen levels do not correlate with improvement in cognition.

OBJECTIVE: To investigate whether an association exists between estradiol and estrone levels and measures of cognitive functioning in women with Alzheimer disease (AD) treated with conjugated equine estrogen (Premarin; Wyeth-Ayerst, Philadelphia, Pa). METHODS: We studied 120 postmenopausal women who underwent hysterectomy and who had AD treated with Premarin for 1 year. Plasma estradiol and estrone levels were determined at multiple points during the 1-year treatment trial. The change from baseline level at 2 and 12 months was associated with the change score on 7 different assessments of cognitive functioning. RESULTS: At baseline, estradiol levels were low and there were no associations between the estradiol level and the 7 neuropsychological measures. A similar pattern was observed for estrone treatment. During treatment with 0.625 mg/d of Premarin, estradiol levels increased about 4-fold; while receiving 1.25 mg/d of Premarin, estradiol levels increased about 8-fold. A similar pattern was seen with estrone treatment. For both estradiol and estrone levels, there were no significant associations between the change in plasma level and the change in neuropsychological test scores at either 2 or 12 months. CONCLUSION: Although Premarin elevated estradiol and estrone levels, there was no association between hormone levels and cognitive functioning after either 2 or 12 months of treatment.

Aged↗

PubMed2003

The effects of galantamine treatment on caregiver time in Alzheimer's disease.

AIM: The aim of the study was to determine whether the clinical benefits of galantamine for patients with Alzheimer's disease lead to benefits for caregivers. METHODS: Data were pooled from two concurrent, multi-centre, randomized, double-blind, placebo-controlled, 6-month trials. Time caregivers spent assisting with activities of daily living (ADL) and time patients could be left unsupervised each day were assessed using the Allocation of Caregiver Time Survey. In total, 825 patients with mild-to-moderate Alzheimer's disease were included. RESULTS: At endpoint, caregivers of galantamine-treated patients were more likely to report reductions (41% vs 37%), maintenance (19% vs 14%) or smaller increases (26% vs 34% reporting an increase >30 minutes) in time assisting with ADL compared with the placebo group (p=0.026; Wilcoxon rank-sum test). The mean daily time difference was 32 minutes (p=0.011). Among patients with moderate Alzheimer's disease, caregivers of galantamine-treated patients were even more likely to report reductions (46% vs 37%), maintenance (15% vs 6%) or smaller increases (25% vs 42% for increases >30 min) vs placebo (p=0.004), with a mean daily time saving of 53 minutes (p=0.021). Caregivers of galantamine-treated patients were more likely to report increases (22% vs 18%), maintenance (45% vs 43%) or smaller reductions (30% vs 37% for reductions >30 minutes) in time the patient could be left unsupervised compared with placebo (p=0.027). Mean daily time saving was 27 minutes. Among patients with moderate Alzheimer's disease, the treatment effect was greater (p=0.029), with caregivers in the galantamine group reporting the change in time left unsupervised as 68 minutes longer each day than caregivers of patients receiving placebo. CONCLUSION: The clinical benefits of galantamine for patients with Alzheimer's disease are also associated with benefits to caregiving.

Activities of Daily Living↗

PubMed2003

Current concepts in the prevention of Alzheimer's disease.

Alzheimer's disease represents a significant challenge to the aging population. Since most estimates suggest that AD has a multifactorial etiology, the challenge to find preventative approaches is particularly great. With the aging of the population and the very high incidence from the eighth decade on, the challenge is further enhanced by the need to think of relatively safe interventions given the relative frailty of this elderly population. The need to find safe treatments, or ones with well-understood safety profiles, has led to the examination of known agents for potential dementia-preventing properties. Data supporting these interventions comes from observational studies, laboratory analyses, and clinical trials. Potential mechanisms for prevention of AD include anti-inflammatory and antioxidant approaches. Modulation of risk factors associated with cardiac disease may also reduce the risk of AD. Known agents have been examined for their potential to modify amyloid pathology. Trial designs to address prevention of AD include both primary and secondary prevention studies as well designs to assess slowing disease progression. Information can also be gathered when dementia evaluation is added to ongoing studies. As results from these studies becoming available, we will be able to refine our approach to managing this disease.

Adult↗

PubMed2003

Ischemic stroke and depression.

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 +/- 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 +/- 6.7 years). We required a SIGH-D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH-D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke.

Aged↗

PubMed2003

Neurocognitive assessment in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project schizophrenia trial: development, methodology, and rationale.

Patients with schizophrenia are severely impaired in crucial aspects of neurocognitive function. This impairment is the strongest clinical correlate of poor long-term outcome and adaptive dysfunction. Reports of neurocognitive enhancement with second generation antipsychotic medications have thus offered promise for improvement in the long-term outcome of patients with schizophrenia. However, the majority of these studies have had serious weaknesses in methodology, such as open-label design, small samples, or inappropriate dosing of medications. More recent studies have addressed these methodological issues but have been of short duration and have largely been sponsored by pharmaceutical companies. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project is a unique opportunity to address the comparative neurocognitive effectiveness of available antipsychotic medications. This article describes the neurocognitive methods used in the schizophrenia trial of the CATIE project, including the selection and training of neurocognitive raters, patient inclusion criteria for assessment, rationale for the choice of neurocognitive instruments, and methodology for each neurocognitive test.

Antipsychotic Agents↗