OBJECTIVES:Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard.
METHODS:Data from the Arizona Study of Aging and ...Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard.
RESULTS:Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia.
CONCLUSIONS:Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 yearsʼ duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced.
CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%.
Sex differences in Alzheimer's disease (AD) may contribute to disease heterogeneity and affect prevalence, risk factors, disease trajectories and outcomes. Depression impacts a large number of ...patients with AD and has been reported to be more prevalent in women. We aimed to better understand the interaction between sex, depression and AD neuropathology, which could have implications for detection of symptoms, earlier diagnosis, therapeutic management, and enhanced quality of life.
We compared 338 cases with clinicopathologically confirmed AD (46% women) to 258 control cases (50% women), without dementia, parkinsonism or a significant pathological diagnosis. Depression was assessed both, using the Hamilton Depression Scale (HAM-D), and as being reported in their medical history combined with treatment with antidepressant medication.
In the control group, women showed a higher depression severity, and a higher proportion of women were found to meet the cut-off score for depression on the HAM-D (32 vs. 16%) and having an history of depression (33 vs. 21%), while these sex differences were not observed in AD. Further, in both groups, female sex independently predicted the presence of depression, with covariates for age and cognitive status. AD subjects had higher mean HAM-D scores, were more likely to meet cutoff scores for depression (41 vs. 24%) and have a history of depression than controls (47 vs. 27%). When comparing the increase in frequency of depression in controls versus AD, the difference was significantly greater in men (AD men - control men: 24%) than in women (AD women - control women: 9%). Although subjects with depression were more likely to have higher levels of AD neuropathology, these differences were not observed when investigating the control or AD group separately.
Control women had a higher likelihood and severity of depression than control men, but this sex difference was not noted when considering only those with pathologically defined AD, emphasizing the importance of considering sex in aging studies. AD was associated with higher rates of depression and men may be more likely to report or be diagnosed with depression once they develop AD indicating the importance of more frequent depression screenings in men.
Abstract
This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data ...from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research clinical assessment, including subspecialty neurologist-administered movement and cognitive evaluation. Of the 280, 25.7% were cognitively normal, 8.6% had mild cognitive impairment, and 65.7% had dementia. All cases could be categorized into 1 of 5 USSLB stages (8.6% stage I—olfactory bulb only; 15.4% IIa—brainstem predominant; 13.6% IIb—limbic predominant; 31.8% III—brainstem and limbic; and 30.7% IV—neocortical) yet using the Braak staging system 70 cases (25.3%) could not be classified. Those with USSLB stages III and IV died at a younger age. Multiple measures of motor parkinsonism, cognitive impairment, hyposmia, and probable RBD were significantly correlated with increasing USSLB stage. We conclude that the USSLB is the most comprehensive staging system for all Lewy body disorders and allows for categorization and ranking of all brains with significant correlations to many motor and nonmotor clinical signs and symptoms.
The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain‐only donations and currently has banked more ...than 1600 brains. More than 430 whole‐body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0‐hour median post‐mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant‐funded projects.
Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains ...controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.
Abstract Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of ...LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer’s disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.
The utility of plasma amyloid beta (Aβ) and tau levels for the clinical diagnosis of Alzheimer's disease (AD) dementia has been controversial. The main objective of this study was to compare Aβ42 and ...tau levels measured by the ultra-sensitive immunomagnetic reduction (IMR) assays in plasma samples collected at the Banner Sun Health Institute (BSHRI) (United States) with those from the National Taiwan University Hospital (NTUH) (Taiwan). Significant increase in tau levels were detected in AD subjects from both cohorts, while Aβ42 levels were increased only in the NTUH cohort. A regression model incorporating age showed that tau levels identified probable ADs with 81 and 96% accuracy in the BSHRI and NTUH cohorts, respectively, while computed products of Aβ42 and tau increased the accuracy to 84% in the BSHRI cohorts. Using 382.68 (pg/ml)
as the cut-off value, the product achieved 92% accuracy in identifying AD in the combined cohorts. Overall findings support that plasma Aβ42 and tau assayed by IMR technology can be used to assist in the clinical diagnosis of AD.
Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer's disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with ...Lewy bodies (AD-DLB) or Alzheimer's disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course.
Subjects with dementia included those with "pure" ADD (n = 137), AD-DLB (n = 64) and AD-LB (n = 114), all with two or more complete Mini Mental State Examinations (MMSE) and a full neuropathological examination.
Linear mixed models assessing MMSE change showed that the AD-LB group had significantly greater decline compared to the ADD group (β = -0.69, 95% CI: -1.05, -0.33, p<0.001) while the AD-DLB group did not (β = -0.30, 95% CI: -0.73, 0.14, p = 0.18). Of those with AD-DLB and AD-LB, only 66% and 2.1%, respectively, had been diagnosed with LBD at any point during their clinical course. Compared with clinically-diagnosed AD-DLB subjects, those that were clinically undetected had significantly lower prevalences of parkinsonism (p = 0.046), visual hallucinations (p = 0.0008) and dream enactment behavior (0.013).
The probable cause of LBD clinical detection failure is the lack of a sufficient set of characteristic core clinical features. Core DLB clinical features were not more common in AD-LB as compared to ADD. Clinical identification of ADD with LBD would allow stratified analyses of ADD clinical trials, potentially improving the probability of trial success.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The original validation study for the Montreal Cognitive Assessment (MoCA) suggests a cutoff score of 26; however, this may be too stringent for older adults, particularly for those with less ...education. Given the rapidly increasing number of older adults and associated risk of dementia, this study aims to provide appropriate age- and education-adjusted norms for the MoCA. Data from 205 participants in an ongoing longevity study were used to derive normative data. Individuals were grouped based on age (70-79, 80-89, 90-99) and education level (≤12 Years, 13-15, ≥16 Years). There were significant differences between age and education groups with younger and more educated participants outperforming their counterparts. Forty-six percent of our sample scored below the suggested cutoff of 26. These normative data may provide a more accurate representation of MoCA performance in older adults for specific age and education stratifications.
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