Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
Add more filters










Publication year range
1.
Alzheimers Dement ; 7(5): 509-13, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21723206

ABSTRACT

BACKGROUND: Normal pressure hydrocephalus (NPH) is considered to be potentially treatable with the placement of a cerebrospinal fluid (CSF) shunt. However, the procedure has been reported to have variable success, particularly with respect to improving the cognitive impairment in NPH. The presence of neurologic comorbidities, particularly Alzheimer's disease (AD), may contribute to shunt responsiveness. Uncovering the extent to which AD and NPH co-occur has implications for diagnosis and treatment of NPH. Autopsy studies of patients with NPH during their lifetime would elucidate the frequency of such comorbidities. METHODS: A search of the Sun Health Research Institute Brain Donation Program database was conducted between January 1, 1997 and April 1, 2009 to identify all cases with neuropathologic evidence of dementia as well as those of clinically diagnosed NPH. We reviewed the medical records and brain findings of each NPH case. RESULTS: Of the 761 cases autopsied over the study interval, 563 were found to have neuropathologic evidence meeting criteria for a dementing illness. Of 563 cases, AD was found exclusively in 313 (56%), and 94 suffered from secondary diagnosis of dementia. Nine of 761 cases were identified with a clinical diagnosis of NPH, which were among the 563 cases with neuropathology of dementing illness at autopsy, representing 1.6% (9/563) of the cases. On review of brain autopsy reports of these nine patients, eight (89%) were found to have AD and one (11%) had progressive supranuclear palsy. Review of the medical records of the nine NPH cases revealed the following clinical comorbidities: five suffered from AD, one from Parkinson's Disease, one from mild cognitive impairment, and one from seizure disorder. CONCLUSIONS: Given the findings of the present study, we support the AD-NPH theory and posit that AD is a common pathologic comorbidity in the setting of NPH and may preclude cognitive improvement postshunt placement. This may influence the selection of cases for shunting in the future.


Subject(s)
Alzheimer Disease/epidemiology , Alzheimer Disease/pathology , Hydrocephalus, Normal Pressure/epidemiology , Hydrocephalus, Normal Pressure/pathology , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Autopsy , Brain/pathology , Brain/physiopathology , Cognition Disorders/epidemiology , Cognition Disorders/pathology , Cognition Disorders/physiopathology , Comorbidity , Female , Humans , Hydrocephalus, Normal Pressure/physiopathology , Male , Prevalence , Retrospective Studies
2.
Alzheimers Dement ; 7(4): 445-55, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21388892

ABSTRACT

BACKGROUND: Multiple lines of evidence suggest that cardiovascular co-morbidities hasten the onset of Alzheimer's disease (AD) or accelerate its course. METHODS: To evaluate the utility of cerebral vascular physical function and/or condition parameters as potential systemic indicators of AD, transcranial Doppler (TCD) ultrasound was used to assess cerebral blood flow and vascular resistance of the 16 arterial segments comprising the circle of Willis and its major tributaries. RESULTS: Our study showed that decreased arterial mean flow velocity and increased pulsatility index are associated with a clinical diagnosis of presumptive AD. Cerebral blood flow impairment shown by these parameters reflects the global hemodynamic and structural consequences of a multifaceted disease process yielding diffuse congestive microvascular pathology, increased arterial rigidity, and decreased arterial compliance, combined with putative age-associated cardiovascular output declines. CONCLUSIONS: TCD evaluation offers direct physical confirmation of brain perfusion impairment and might ultimately provide a convenient and a noninvasive means to assess the efficacy of medical interventions on cerebral blood flow or reveal incipient AD. In the near term, TCD-based direct assessments of brain perfusion might offer the prospect of preventing or mitigating AD simply by revealing patients who would benefit from interventions to improve circulatory system function.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/physiopathology , Cerebrovascular Circulation/physiology , Ultrasonography, Doppler, Transcranial , Aged , Aged, 80 and over , Blood Flow Velocity/physiology , Circle of Willis/diagnostic imaging , Circle of Willis/pathology , Female , Humans , Male , Mental Status Schedule , Middle Aged , ROC Curve
3.
Acta Neuropathol ; 119(6): 689-702, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20306269

ABSTRACT

A sensitive immunohistochemical method for phosphorylated alpha-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson's disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer's disease with Lewy bodies (ADLB) and 17 with Alzheimer's disease with no Lewy bodies (ADNLB). The relative densities and frequencies of occurrence of phosphorylated alpha-synuclein histopathology (PASH) were tabulated and correlated with diagnostic category. The greatest densities and frequencies of PASH occurred in the spinal cord, followed by the paraspinal sympathetic ganglia, the vagus nerve, the gastrointestinal tract and endocrine organs. The frequency of PASH within other organs and tissue types was much lower. Spinal cord and peripheral PASH was most common in subjects with PD and DLB, where it appears likely that it is universally widespread. Subjects with ILBD had lesser densities of PASH within all regions, but had frequent involvement of the spinal cord and paraspinal sympathetic ganglia, with less-frequent involvement of end-organs. Subjects with ADLB had infrequent involvement of the spinal cord and paraspinal sympathetic ganglia with rare involvement of end-organs. Within the gastrointestinal tract, there was a rostrocaudal gradient of decreasing PASH frequency and density, with the lower esophagus and submandibular gland having the greatest involvement and the colon and rectum the lowest.


Subject(s)
Alzheimer Disease/metabolism , Lewy Body Disease/metabolism , Parkinson Disease/metabolism , alpha-Synuclein/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Brain/metabolism , Brain/pathology , Female , Ganglia, Sympathetic/metabolism , Ganglia, Sympathetic/pathology , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology , Humans , Immunohistochemistry , Lewy Body Disease/pathology , Male , Parkinson Disease/pathology , Peripheral Nervous System/metabolism , Peripheral Nervous System/pathology , Phosphorylation , Spinal Cord/metabolism , Spinal Cord/pathology
4.
Alzheimer Dis Assoc Disord ; 23(3): 229-33, 2009.
Article in English | MEDLINE | ID: mdl-19812464

ABSTRACT

Argyrophilic grains (AGs) are a pathologic feature found in association with neurodegenerative disease. Some have suggested that these features may occur as a distinctive condition. We reviewed 80 subjects from our tissue bank with pathologically confirmed AGs and identified their clinical features. We compared these subjects' features to the features of subjects with matched clinical diagnoses but without AGs. Subjects with AGs represented 21.7% of the entire autopsy sample from 1999 to 2005 (80 out of 367). Of Alzheimer disease (AD) subjects, 43 out of 233 had AGs (18.4% of AD subjects); 11 out of 42 Parkinson disease with dementia subjects had AGs (26.1% of Parkinson disease with dementia subjects); 2 out of 9 dementia with Lewy bodies subjects had AGs (22.2% of dementia with Lewy bodies subjects); 4 out of 15 mild cognitive impairment subjects had AGs (26.7% of mild cognitive impairment subjects); and 20 out of 68 cognitively normal subjects had AGs (29.4% of cognitively normal). Subjects with AGs tended to be older but only significantly so in AD. Many comorbid non-neurologic health conditions were seen in cases of AGs without any single predilection emerging. AGs occur in approximately 22% of the entire autopsy cohort and are likely associated with advanced age. No distinctive antemortem clinical features were over represented in the AG cases. AGs can occur with or without neurodegenerative conditions and can occur in the absence of significant cognitive decline. AGs are not clearly associated with any single comorbid health condition.


Subject(s)
Aging/pathology , Brain/pathology , Inclusion Bodies/pathology , Neurodegenerative Diseases/pathology , Aged, 80 and over , Autopsy , Female , Humans , Male
5.
Alzheimer Dis Assoc Disord ; 23(3): 295-7, 2009.
Article in English | MEDLINE | ID: mdl-19812474

ABSTRACT

Subjects with Parkinson disease (PD) frequently develop dementia with greater than one-third meeting neuropathologic diagnostic criteria for Alzheimer disease (AD). The objective is to identify clinical and neuropathologic differences between Parkinson disease with dementia (PDD) subjects, with and without coexistent AD pathology. Neuropathologic examination was available on subjects diagnosed by clinicopathologic criteria with PDD-AD (N=23) and PDD+AD (N=28). A small subset of subjects with PDD-AD and PDD+AD had received at least 1 standardized neuropsychologic assessment. PDD+AD subjects were significantly older at age of PD onset and death, progressed to onset of dementia in less time, and had a shorter duration of PD symptoms before the onset of dementia. Education, responsiveness of L-dopa and dopaminergic medications, presence of cognitive fluctuations and hallucinations, and mean Mini-Mental State Examination, Global Deterioration Scale, Functional Assessment Staging, and Unified Parkinson Disease Rating Scale scores did not differ significantly between the 2 groups. The PDD+AD group had significantly greater total plaques, neuritic plaques, total tangles, and Braak stages compared with PDD-AD. This study suggests that it is difficult to distinguish PDD+AD and PDD-AD on the basis of movement, clinical, and neuropsychologic assessment. PDD-AD and PDD+AD have similar degrees of dementia and approximately half of PDD subjects have enough AD pathology to attain a neuropathologic diagnosis of AD. PDD can develop in the absence of significant Alzheimer pathology.


Subject(s)
Alzheimer Disease/pathology , Dementia/pathology , Parkinson Disease/pathology , Aged , Aged, 80 and over , Alzheimer Disease/complications , Dementia/complications , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/complications
6.
J Ultrasound Med ; 28(11): 1493-500, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19854964

ABSTRACT

OBJECTIVE: There is considerable epidemiologic evidence that Alzheimer disease (AD) is linked to cardiovascular risk factors and associated with an increased risk of symptomatic left ventricular (LV) dysfunction. Formation of a vortex alongside a diastolic jet signifies an efficient blood transport mechanism. The vortex formation time (VFT) is an index of optimal conditions for vortex formation. We hypothesized that AD and its associated cardiovascular risk factors impair diastolic transmitral flow efficiency and, therefore, shift the VFT value out of its optimal range. METHODS: Echocardiographic studies were performed on 45 participants in total: 22 patients with AD diagnosed according to the American Psychiatric Association's criteria and 23 age-matched individuals as a control group with cognitive function within normal limits. RESULTS: The echocardiographic ratio of the early to atrial phases of the LV filling velocities was significantly lower in the AD group (mean +/- SD, 0.67 +/- 14) when compared with the control individuals (0.79 +/- 0.14; P = .003). The interventricular septum diastolic thickness, left ventricular posterior wall diastolic thickness, and right ventricular end-diastolic diameter were significantly higher in the AD group (P

Subject(s)
Alzheimer Disease/physiopathology , Blood Flow Velocity , Mitral Valve/physiopathology , Stroke Volume , Ventricular Dysfunction, Left/physiopathology , Aged , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Echocardiography/methods , Female , Humans , Male , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology
7.
Mov Disord ; 24(12): 1840-2, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19609905

ABSTRACT

Restless legs syndrome is a common disorder that may interrupt sleep and has been reported to produce daytime fatigue and/or mood changes. This study assessed whether patients with RLS have more cognitive dysfunction and depression than individuals of the same age and education who do not have RLS. The study showed that older individuals with mild RLS for at least 1 year do not have cognitive dysfunction and are not depressed compared with a control group of similar age and education.


Subject(s)
Cognition Disorders/etiology , Depression/etiology , Restless Legs Syndrome/complications , Aged , Aged, 80 and over , Humans , Neuropsychological Tests , Polysomnography , Psychiatric Status Rating Scales , Restless Legs Syndrome/drug therapy , Severity of Illness Index
8.
Cell Tissue Bank ; 9(3): 229-45, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18347928

ABSTRACT

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability.


Subject(s)
Academies and Institutes , Brain , Tissue Banks , Tissue and Organ Procurement , Arizona , Databases, Nucleic Acid , History, 20th Century , History, 21st Century , Humans , Postmortem Changes , Tissue Banks/history , Tissue Donors , Tissue Preservation , Tissue Survival , Tissue and Organ Procurement/history
9.
Neurol Res ; 28(6): 672-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16945221

ABSTRACT

OBJECTIVE: Recent post-mortem studies have reported that the severity of atheromatous deposits in the circle of Willis is significantly greater, relative to non-demented (ND) elderly persons, in subjects with neuropathologically diagnosed Alzheimer's disease (AD). Additionally, the severity of intracranial atherosclerosis correlates significantly with the densities of neuritic plaques and neurofibrillary tangles. In this study, we examine the arteries of the circle of Willis by transcranial Doppler (TCD) ultrasonography. METHODS: TCD was used to measure, in 25 AD patients and 30 ND elderly subjects, mean flow velocities and pulsatility indices in 16 different segments of the circle of Willis. The data were compared with and without adjustment for age, gender and systolic blood pressure. RESULTS: The AD patients had systematically higher pulsatility indices (p<0.005) than the ND group. Incremental increases of pulsatility indices in these segments had odds ratios ranging from 1.8 to 48 for the presence of AD when adjusted for age, gender and systolic blood pressure. The left internal carotid artery siphon and the left posterior cerebral artery were the two vessels that were strongly associated with AD diagnosis. Mean flow velocities were generally lower in patients with AD but the differences did not reach the significance level. DISCUSSION: The pulsatility indices of the arteries of AD patients were generally greater than those of similarly-aged ND subjects. This difference is most likely due to increased arterial wall rigidity imposed by atherosclerotic changes. Atherosclerotic disease of intracranial arteries may be a risk factor for AD.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/pathology , Ultrasonography, Doppler, Transcranial , Aged , Aged, 80 and over , Alzheimer Disease/complications , Anterior Cerebral Artery/diagnostic imaging , Cardiovascular Diseases/complications , Cerebrovascular Circulation , Circle of Willis/diagnostic imaging , Female , Humans , Male , Nerve Degeneration/complications , Nerve Degeneration/diagnostic imaging , Nerve Degeneration/pathology , Posterior Cerebral Artery/diagnostic imaging
10.
Neurobiol Aging ; 27(12): 1733-9, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16290270

ABSTRACT

Brain deposits of amyloid beta peptide (Abeta) have been a diagnostic hallmark of Alzheimer's disease (AD) for nearly a century. Recent studies have demonstrated that Abeta is also present in peripheral blood. Here, we present evidence that circulating Abeta42 is subject to complement C3b-dependent adherence to complement receptor 1 (CR1) on erythrocytes, a classical set of mechanisms by which pathogens and proteins recognized as foreign are cleared from the bloodstream. Levels of Abeta42 targeted by this pathway differ significantly in AD compared to mild cognitive impairment and nondemented elderly controls.


Subject(s)
Amyloid beta-Peptides/blood , Complement C3/physiology , Erythrocytes/metabolism , Peptide Fragments/blood , Alzheimer Disease/blood , Cell Adhesion/immunology , Humans , Protein Transport/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...