Biomedical subjects

S M Greenberg

Publications and source records attributed to S M Greenberg.

At least 19 recordsLinked to original sources

PubMed2006

Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy.

OBJECTIVE: To determine the rate of progression of white matter lesions and hemorrhages in a cohort with cerebral amyloid angiopathy (CAA). METHODS: The authors analyzed data from 26 patients with possible (3) or probable (23) CAA, diagnosed by the Boston Criteria. Brain maps of white matter hyperintensities, normalized to head size (nWMH), were created by blinded computer-assisted segmentation of MRI images obtained at baseline and after a median follow-up interval of 1.1 year. RESULTS: There was a substantial nWMH volume increase over the interscan interval (median 0.5 mL/year, interquartile range 0.1 to 2.8, p < 0.001). The median yearly increase, expressed as a percentage of the baseline WMH volume, was 18%. The characteristic most strongly associated with nWMH volume increase was the baseline nWMH volume (r = 0.57, p = 0.002). The volume of nWMH progression was also associated with history of cognitive impairment (median 5.0 mL/year in cognitively impaired subjects vs 0.3 mL/year in cognitively unimpaired, p = 0.02) but not age or hypertension. This association remained present in an analysis stratified by baseline WMH volume. New hemorrhages, including asymptomatic microbleeds, were seen in 46% of subjects. The number of new MRI hemorrhages correlated strongly with baseline nWMH (r = 0.53, p = 0.005) but not with nWMH progression (r = 0.22, p = 0.28). CONCLUSIONS: There is a progressive increase in white matter lesions in subjects with cerebral amyloid angiopathy. The association of white matter lesions with incident lobar hemorrhages suggests that white matter damage may reflect a progressive microangiopathy due to cerebral amyloid angiopathy.

Aged↗

PubMed2006

Antiplatelet use after intracerebral hemorrhage.

BACKGROUND: Survivors of intracerebral hemorrhage are at risk for recurrent intracerebral hemorrhage and ischemic cardiovascular and cerebrovascular disease. OBJECTIVE: To determine whether antiplatelet therapy increases the risk of recurrent intracerebral hemorrhage. METHODS: The authors reviewed data from consecutive survivors of primary intracerebral hemorrhage enrolled in a single-center prospective cohort study. Survivors were followed by telephone interview; recurrent intracerebral hemorrhage and post-index antiplatelet agent use and duration were recorded. Cox proportional hazards models was used with antiplatelet agent exposure as a time-dependent variable to assess the effect of antiplatelet agent use on recurrent intracerebral hemorrhage, stratified by lobar and deep hemispheric location. RESULTS: Recurrent intracerebral hemorrhage was more common in survivors of lobar hemorrhage compared with survivors of deep hemorrhage (cumulative 2-year rate 22% vs 4%; p = 0.007). Antiplatelet agents were prescribed in 22% of intracerebral hemorrhage survivors (27/127 lobar, 19/80 deep hemispheric), most commonly for prevention of ischemic heart disease. Antiplatelet agent use was not associated with intracerebral hemorrhage recurrence in survivors of either lobar hemorrhage (hazard ratio [HR] 0.8, 95% CI 0.3 to 2.3, p = 0.73) or of deep hemorrhage (HR 1.2, 95% CI 0.1 to 14.3, p = 0.88). CONCLUSION: Antiplatelet agent use is relatively common following intracerebral hemorrhage but did not appear to be associated with a large increased risk of intracerebral hemorrhage recurrence in this observational study.

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PubMed2006

Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy.

BACKGROUND: Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating beta-amyloid peptide in microvascular dysfunction and white matter disease. METHODS: The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of beta-amyloid (Abeta40 and Abeta42) detected by specific enzyme-linked immunosorbent assays. RESULTS: Plasma Abeta40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p < or = 0.005). Plasma Abeta40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Abeta40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons). CONCLUSIONS: Plasma beta-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly.

Aged↗

PubMed2006

Current pharmacotherapy for Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects approximately 4.5 million people in the United States. The mainstays of current pharmacotherapy for AD are compounds aimed at increasing the levels of acetylcholine in the brain, thereby facilitating cholinergic neurotransmission through inhibition of the cholinesterases. These drugs, known as acetylcholinesterase inhibitors (AChEIs), were first approved by the U.S. Food and Drug Administration (FDA) in 1995 based on clinical trials showing modest symptomatic benefit on cognitive, behavioral, and global measures. In 2004 the FDA approved memantine, an NMDA antagonist, for treating dementia symptoms in moderate to severe AD cases. In clinical practice, memantine may be co-administered with an AChEI, although neither drug individually or in combination affects the underlying pathophysiology of dementia. Dementia in AD results from progressive synaptic loss and neuronal death. As knowledge of the mechanisms responsible for neurodegeneration in AD increases, it is anticipated that neuroprotective drugs to slow or prevent neuronal dysfunction and death will be developed to complement current symptomatic treatments.

Alzheimer Disease↗

PubMed2005

Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease.

BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases. OBJECTIVE: To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD). METHODS: Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88). RESULTS: The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001). CONCLUSIONS: Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.

Aged↗

PubMed2005

Prevalence and effects of lobar microhemorrhages in early-stage dementia.

BACKGROUND: 80-100% of patients with Alzheimer's disease have vascular pathology related to cerebral amyloid angiopathy (CAA), and 5-7% have CAA-related lobar microhemorrhages (LMH) at autopsy. The prevalence and effects of LMH detectable by gradient echo MRI (GE-MRI) in early-stage dementia are unknown. OBJECTIVE: To obtain, using GE-MRI, a prevalence estimate for LMH in patients with early-stage dementia and to assess the effects of LMH on dementia severity. METHODS: Eighty-four subjects aged >or=55 years (range 58-89; mean 76) underwent cognitive and GE-MRI evaluation. The 84 subjects consisted of 61 consecutive subjects evaluated as part of an initial clinical evaluation for dementia and 23 consecutively evaluated healthy older subjects (controls). Data were analyzed for presence and number of LMH on GE-MRI and the effect of number of LMH on dementia severity. RESULTS: Nine (15%) of the 61 dementia patients versus 1 (4%) of the 23 control subjects demonstrated LMH on GE-MRI. Multiple (>or=2) LMH were found in 7 of the 9 (88%) dementia subjects with LMH (range of LMH counts 1-330) and no (0%) control subjects. Multivariable causal modeling indicated that number of LMH (p < 0.02), age (p < 0.01) and duration of symptoms (p < 0.001) significantly increased dementia severity while higher educational level (p < 0.001) was protective. CONCLUSIONS: LMH were detected by GE-MRI in 15% of patients with early-stage dementia and may contribute to dementia severity.

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PubMed2005

Size-dependent feeding and reproduction by boll weevil (Coleoptera: Curculionidae).

The considerable variation in adult size of the boll weevil, Anthonomus grandis grandis Boheman, has been well documented, but the influences of adult size on reproductive rate are not known. We examined the relationship between the size of boll weevils and their feeding and oviposition. Weevils weighed to the nearest milligram were grouped into five categories based on pupal weight: < or =5, 6-10, 11-15, 16-20, and >20 mg. Numbers of lifetime punctures produced in flower buds (squares) of cotton, Gossypium hirsutum L., by both sexes of adults tended to increase with pupal weight. Boll weevil females with pupal weights >10 mg produced progeny with significantly higher survival to adulthood and also produced a higher percentage of female progeny than those with pupal weights < or =10 mg. The population growth indices for females having pupal weights >10 mg averaged 1.8-fold higher than those of females weighing < or =10 mg. Survivorship of adults of both sexes also tended to increase with pupal weight. The percentage of females laying eggs on any given day averaged 2.1 times higher when their pupal weights were >10 mg than when their pupal weights were < or =10 mg. Although small size negatively affected female reproductive potential, even extremely small females produced some viable offspring. However, the penalties of small adult size, in terms of longevity and reproductive potential, suggest that cultural practices that result in the production of small adults may be used to impact weevil populations.

Animals↗

PubMed2005

Effects of planting dates on boll weevils (Coleoptera: Curculionidae) and cotton fruit in the subtropics.

The effects of planting dates 2-3-wk apart on boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), field-level populations, and feeding and oviposition damage to cotton, Gossypium hirsutum L., squares and bolls, were studied during 2002 and 2003 in the Lower Rio Grande Valley of Texas. Squares were 44-56% more abundant in some later planted treatments than in the earlier planted treatments, but mean cumulative numbers of oviposition- and feeding-damaged squares were 2.7 - 4.8-fold greater in some later planted treatments than in earlier treatments. Increased square production in later planted cotton was offset by boll weevil infestations that occurred when squares are most vulnerable and contribute most toward the pest's reproduction. Early planting avoided boll weevil population buildups in the field when large squares were abundant. Lint yields in 2002 did not differ significantly between the planting date treatments, but in 2003, mean yield in the middle treatment was 23% greater than in the early and late-planted treatments. Insecticide sprays in the earliest planted treatment of each year, based on the 10% damaged squares threshold, were >33% and >43% fewer than in the corresponding middle and latest planting treatments, respectively. Delayed planting, relative to the onset of favorable cotton-growing weather, at the field level, even when not applied uniformly on an areawide scale, is more cost-effective than planting too early or too late.

Agriculture↗

PubMed2004

White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage.

BACKGROUND: Accumulating evidence suggests that white matter lesions are associated with vascular cognitive impairment. The authors investigated the relationships between white matter lesions, cognitive impairment, and risk of recurrent hemorrhage in a prospectively identified cohort of patients with lobar intracerebral hemorrhage (ICH). METHODS: The authors collected clinical and genetic information on 182 consecutive patients age > or = 55 who had CT scan at admission for lobar ICH. White matter disease was graded on CT in all subjects and on MRI in a subset of 82 patients. All scans were interpreted blinded to clinical information. Survivors were followed for recurrent ICH by telephone interview. RESULTS: White matter damage was common (present on CT in 77%) and severe (advanced CT grade in 32%). White matter damage was correlated with the total number of hemorrhages on gradient-echo MRI and with risk of recurrent ICH. Subjects with cognitive impairment prior to their index ICH were more likely to have severe white matter damage on CT (OR 3.6, 95% CI 1.6 to 8.1, p = 0.003) and more likely to have advanced periventricular hyperintensities on MRI. The relationships between white matter damage and cognitive impairment were similar in the subset of 88 subjects meeting criteria for probable or definite cerebral amyloid angiopathy and remained independent after adjustment for age, cortical atrophy, and APOE genotype. CONCLUSIONS: White matter damage in lobar ICH is common and is associated with cognitive impairment. These data support the possibility that an underlying vasculopathy in lobar ICH patients, possibly cerebral amyloid angiopathy, can cause clinically important vascular dysfunction.

Cerebral Amyloid Angiopathy↗

PubMed2004

Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage.

BACKGROUND: Warfarin increases mortality of intracerebral hemorrhage (ICH). The authors investigated whether this effect reflects increased baseline ICH volume at presentation or increased ICH expansion. METHODS: Subjects were drawn from an ongoing prospective cohort study of ICH outcome. The effect of warfarin on baseline ICH volume was studied in 183 consecutive cases of supratentorial ICH age > or = 18 years admitted to the emergency department over a 5-year period. Baseline ICH volume was determined using computerized volumetric analysis. The effect of warfarin on ICH expansion (increase in volume > or = 33% of baseline) was analyzed in 70 consecutive cases in whom ICH volumes were measured on all subsequent CT scans up to 7 days after admission. Multivariable analysis was used to determine warfarin's influence on baseline ICH, ICH expansion, and whether warfarin's effect on ICH mortality was dependent on baseline volume or subsequent expansion. RESULTS: There was no effect of warfarin on initial volume. Predictors of larger baseline volume were hyperglycemia (p < 0.0001) and lobar hemorrhage (p < 0.0001). Warfarin patients were at increased risk of death, even when controlling for ICH volume at presentation. Warfarin was the sole predictor of expansion (OR 6.2, 95% CI 1.7 to 22.9) and expansion in warfarin patients was detected later in the hospital course compared with non-warfarin patients (p < 0.001). ICH expansion showed a trend toward increased mortality (OR 3.5, 95% CI 0.7 to 8.9, p = 0.14) and reduced the marginal effect of warfarin on ICH mortality. CONCLUSIONS: Warfarin did not increase ICH volume at presentation but did raise the risk of in-hospital hematoma expansion. This expansion appears to mediate part of warfarin's effect on ICH mortality.

Adult↗

PubMed2004

Effects of burial and soil condition on postharvest mortality of boll Weevils (Coleoptera: Curculionidae) in fallen cotton fruit.

Effects of soil condition and burial on boll weevil, Anthonomus grandis grandis Boheman, mortality in fallen cotton, Gossypium hirsutum L., fruit were assessed in this study. During hot weather immediately after summer harvest operations in the Lower Rio Grande Valley of Texas, burial of infested fruit in conventionally tilled field plots permitted significantly greater survival of weevils than in no-tillage plots. Burial of infested squares protected developing weevils from heat and desiccation that cause high mortality on the soil surface during and after harvest in midsummer and late summer. A laboratory assay showed that burial of infested squares resulted in significantly greater weevil mortality in wet than in dry sandy or clay soils. Significantly fewer weevils rose to the soil surface after burial of infested bolls during winter compared with bolls set on the soil surface, a likely result of wetting by winter rainfall. A combination of leaving infested fruit exposed to heat before the onset of cooler winter temperatures and burial by tillage when temperatures begin to cool might be an important tactic for reducing populations of boll weevils that overwinter in cotton fields.

Agriculture↗

PubMed2004

Deterrent effects of four neem-based formulations on gravid female boll weevil (Coleoptera: Curculionidae) feeding and oviposition on cotton squares.

Three commercial neem-based insecticides, Agroneem, Ecozin, and Neemix, and a neem seed extract formulation, bitters, containing 1,036, 16,506, 471, and 223 microg/ml azadirachtin, respectively, were assessed for feeding and oviposition deterrence against gravid female boll weevils, Anthonomus grandis grandis Boheman, in the laboratory. In choice assays, excised cotton squares dipped in the separate formulations were first physically contacted by the weevils' tarsi or antennae fewer times than nontreated control squares. In choice and no-choice assays, each formulation repelled the weevils for > or = 90 min. After 24 h in the choice assays, feeding punctures on the squares treated with Agroneem, Ecozin, or bitters were significantly fewer compared with controls. Egg punctures on the Ecozin- and the bitters-treated squares were significantly fewer than on control squares after 24 h. In the no-choice assay, no significant difference was detected. Aging the formulations under outdoor conditions for 24 h before weevils were exposed resulted in 46-60% and 62-82% reductions in feeding and oviposition punctures, respectively, compared with controls. Agroneem- and bitters-treated squares had > 37% fewer feeding punctures after being aged for 48 h. No significant difference was detected after 72 h of aging. Because the deterrence of the gravid female boll weevils was not correlated with amounts of azadirachtin, azadirachtin does not seem to be the only, or the most influential, component of neem that induced the observed deterrence.

Animals↗

PubMed2003

Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation.

The authors searched for mutations in the beta-amyloid precursor protein in a Spanish family with a hereditary syndrome of hemorrhagic stroke, dementia, leukoencephalopathy, and occipital calcifications. DNA from two affected members demonstrated the Iowa amyloid precursor protein mutation previously identified as a cause of severe amyloid angiopathy without hemorrhagic stroke. These data point to other genetic or environmental factors that may determine the occurrence of symptomatic hemorrhage in amyloid angiopathy.

Age of Onset↗

PubMed2003

Alzheimer disease's double-edged vaccine.

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Alzheimer Disease↗

PubMed2002

Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke.

BACKGROUND AND OBJECTIVES: Prior ischemic stroke is a risk factor for intracerebral hemorrhage (ICH) in patients taking warfarin, but the mechanism is not known. This study investigates radiographic and clinical characteristics of patients with warfarin-related ICH following ischemic stroke. METHODS: In this case-control study, the authors selected all patients with warfarin-related ICH and previous symptomatic ischemic stroke from a prospective cohort of consecutive patients with ICH. Control subjects were similarly aged patients with history of symptomatic stroke randomly chosen from an anticoagulant therapy unit. The 26 eligible ICH cases and 56 controls were compared for vascular risk factors, stroke characteristics, and extent of leukoaraiosis (graded in anterior and posterior brain regions on a validated scale of 0 to 4). RESULTS: The presence and severity of leukoaraiosis on CT scan correlated strongly with the occurrence of ICH. Leukoaraiosis was seen in 24 of 26 cases (92%) compared with 27 of 56 controls (48%), yielding an odds ratio of 12.9 (95% CI 2.8 to 59.8). Other clinical factors associated with ICH included an international normalized ratio >3.0, history of multiple previous strokes, and the presence of carotid artery stenosis. The relationship between leukoaraiosis and ICH persisted in multivariable analyses controlling for these risk factors as well as hypertension and diabetes mellitus. CONCLUSIONS: Leukoaraiosis is an independent risk factor for warfarin-related ICH in survivors of ischemic stroke, including those in the commonly employed range of anticoagulation.

Aged↗

PubMed2001

Pathogenic effects of D23N Iowa mutant amyloid beta -protein.

Cerebral amyloid beta-protein angiopathy (CAA) is a key pathological feature of patients with Alzheimer's disease and certain related disorders. In these conditions the CAA is characterized by the deposition of Abeta within the cerebral vessel wall and, in severe cases, hemorrhagic stroke. Several mutations have been identified within the Abeta region of the Abeta protein precursor (AbetaPP) gene that appear to enhance the severity of CAA. We recently described a new mutation within the Abeta region (D23N) of AbetaPP that is associated with severe CAA in an Iowa kindred (Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G., Rebeck, G. W., and Greenberg, S. M. (2001) Ann. Neurol. 49, 697-705). In the present study, we investigated the effect of this new D23N mutation on the processing of AbetaPP and the pathogenic properties of Abeta. Neither the D23N Iowa mutation nor the E22Q Dutch mutation affected the amyloidogenic processing of AbetaPP expressed in H4 cells. The A21G Flemish mutation, in contrast, resulted in a 2.3-fold increase in secreted Abeta peptide. We also tested synthetic wild-type and mutant Abeta40 peptides for fibrillogenesis and toxicity toward cultured human cerebrovascular smooth muscle (HCSM) cells. The E22Q Dutch, D23N Iowa, and E22Q,D23N Dutch/Iowa double mutant Abeta40 peptides rapidly assembled in solution to form fibrils, whereas wild-type and A21G Flemish Abeta40 peptides exhibited little fibril formation. Similarly, the E22Q Dutch and D23N Iowa Abeta40 peptides were found to induce robust pathologic responses in cultured HCSM cells, including elevated levels of cell-associated AbetaPP, proteolytic breakdown of smooth muscle cell alpha-actin, and cell death. Double mutant E22Q,D23N Dutch/Iowa Abeta40 was more potent than either single mutant form of Abeta in causing pathologic responses in HCSM cells. These data suggest that the different CAA mutations in AbetaPP may exert their pathogenic effects through different mechanisms. Whereas the A21G Flemish mutation appears to enhance Abeta production, the E22Q Dutch and D23N Iowa mutations enhance fibrillogenesis and the pathogenicity of Abeta toward HCSM cells.

Amino Acid Sequence↗

PubMed2001

Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria.

The authors performed clinical-pathologic correlation to assess the validity of the Boston diagnostic criteria for cerebral amyloid angiopathy (CAA). Thirteen subjects were diagnosed clinically with probable CAA from among 39 patients with available pathologic tissue in a prospective cohort of subjects aged > or = 55 years with primary lobar hemorrhage. All 13 individuals were confirmed neuropathologically as having CAA. This small pathologic series indicates that the diagnosis of probable CAA can be made during life with high accuracy.

Brain↗

PubMed2001

Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy.

Several mutations in the amyloid precursor protein (APP) gene have been found to associate with pathologic deposition of the beta-amyloid peptide (Abeta) in neuritic plaques or in the walls of cerebral vessels. We report a mutation at a novel site in APP in a three-generation Iowa family with autosomal dominant dementia beginning in the sixth or seventh decade of life. The proband and an affected brother had progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. Neuropathological examination of the proband revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and unusually extensive distribution of Abeta40 in plaques. The affected brothers shared a missense mutation in APP, resulting in substitution of asparagine for aspartic acid at position 694. This site corresponds to residue 23 of Abeta, thus differing from familial Alzheimer's disease mutations, which occur outside the Abeta sequence. Restriction enzyme analysis of DNA from 94 unrelated patients with sporadic cerebral amyloid angiopathy-related hemorrhage found no other instances of this mutation. These results suggest a novel site within Abeta that may promote its deposition and toxicity.

Age of Onset↗