scholarly journals Faster Cognitive Decline in Dementia due to Alzheimer Disease with Clinically Undiagnosed Lewy Body Disease

2019 ◽  
Author(s):  
TG Beach ◽  
M Malek-Ahmadi ◽  
E Zamrini ◽  
CH Adler ◽  
MN Sabbagh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Clinical Features ◽  
Lewy Body ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
High Rate ◽  
Detection Failure

AbstractNeuropathology 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. 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. 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). Clinical identification of ADD with LBD would allow stratified analyses of ADD clinical trials, potentially improving the probability of trial success.

Cognitive decline is faster in Lewy body variant than in Alzheimer's disease

Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 351-357 ◽  
Author(s):  
J. M. Olichney ◽  
D. Galasko ◽  
D. P. Salmon ◽  
C. R. Hofstetter ◽  
L. A. Hansen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Lewy Body ◽  
Average Rate ◽  
Lewy Bodies ◽  
Time Interval ◽  
Similar Amount ◽  
Extrapyramidal Signs ◽  
Lewy Body Variant

Objectives: To quantify the rate of cognitive decline on the Mini-Mental State Examination (MMSE) in autopsy-diagnosed Lewy body variant (LBV) of Alzheimer's disease (AD) cases. We hypothesized that LBV patients would have a faster cognitive decline and shorter survival compared with patients with pure AD.Background: Prior reports have shown extrapyramidal signs to be associated with a poorer prognosis in AD. It has been suggested that LBV is often characterized by a rapidly progressive course. Few data are available regarding the rate of cognitive decline in autopsy-confirmed LBV dementia cases.Methods: We searched the databases of the University of California-San Diego Alzheimer's Disease Research Center and the Consortium to Establish a Registry in Alzheimer's Disease (CERAD) for dementia cases with 1) an autopsy diagnosis of definite or probable AD (CERAD criteria) with concomitant Lewy bodies and 2) longitudinal MMSE assessments. This resulted in a series of 40 LBV cases and 148 AD cases without Lewy bodies, with comparable baseline MMSE scores, age, and education. The rate of cognitive decline was calculated as the baseline MMSE - final MMSE. Methods were devised to reduce floor effects on the MMSE.Results: The average rate of cognitive decline was -5.8 ± 4.5 points/y in LBV and -4.1 ± 3.0 points/y in AD (t-test, p< 0.01). The LBV group declined a similar amount on the MMSE (means, -10.0 versus -9.6 points) over a significantly shorter time interval (1.9 versus 2.7 years; p = 0.005) than did AD patients. At baseline, the mean MMSE scores were nearly identical (18.2 in LBV; 17.8 in AD), but on follow-up examinations approximately 1, 2, and 3 years later, there were intergroup mean differences of 1.8 points (two-tailed p = 0.19), 4.2 points (p = 0.04), and 5.6 points (p = 0.03), respectively. The LBV cases had shorter survival time from the onset of cognitive symptoms (7.7 ± 3.0 years versus 9.3 ± 3.5 years; p = 0.007) and a shorter mean survival after entry/baseline, which was of marginal significance (3.6 versus 4.1 years; p = 0.11).Conclusions: This study demonstrates that LBV is characterized by a faster cognitive decline and accelerated mortality compared with AD.

scholarly journals Diffuse Lewy body disease: clinical features in nine cases without coexistent Alzheimer's disease.

1996 ◽  
Vol 60 (5) ◽  
pp. 531-538 ◽  
Author(s):  
M A Hely ◽  
W G Reid ◽  
G M Halliday ◽  
D A McRitchie ◽  
J Leicester ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Features ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Diffuse Lewy Body Disease

O1-04-07: ″Amygdala predominant″ Lewy body disease: A subtype of Alzheimer's disease with a more aggressive clinical course

2006 ◽  
Vol 2 ◽  
pp. S16-S17
Author(s):  
James B. Leverenz ◽  
Eric B. Larson ◽  
Darcy Vavrek ◽  
Elaine R. Peskind ◽  
James D. Bowen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Clinical Course ◽  
Lewy Body Disease ◽  
Aggressive Clinical Course

scholarly journals Impact of Alzheimer's Disease, Lewy Body and Vascular Co-Pathologies on Clinical Transition to Dementia in a National Autopsy Cohort

2016 ◽  
Vol 42 (1-2) ◽  
pp. 106-116 ◽  
Author(s):  
Jagan A. Pillai ◽  
Robert S. Butler ◽  
Aaron Bonner-Jackson ◽  
James B. Leverenz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Lewy Body ◽  
Functional Decline ◽  
Lewy Body Disease ◽  
Vascular Pathology ◽  
Final Visit ◽  
Clinical Dementia Rating ◽  
National Cohort

Aims: We examined the effect of vascular or Lewy body co-pathologies in subjects with autopsy-confirmed Alzheimer's disease (AD) on the rate of cognitive and functional decline and transition to dementia. Methods: In an autopsy sample of prospectively characterized subjects from the National Alzheimer's Coordinating Center database, neuropathology diagnosis was used to define the groups of pure AD (pAD, n = 84), mixed vascular and AD (ADV, n = 54), and mixed Lewy body disease and AD (ADLBD, n = 31). Subjects had an initial Clinical Dementia Rating-Global (CDR-G) score <1, Mini-Mental State Examination ≥15, a final visit CDR-G >1, ≥3 evaluations, and Braak tangle stage ≥III. We compared the rate of cognitive and functional decline between the groups. Results: The rate of functional and cognitive decline was lower for ADV, and ADV patients had less severe deficits on CDR-G and the CDR-Sum of Boxes scores at the last visit than pAD and ADLBD patients. No significant differences were noted between ADLBD and pAD patients. After controlling for age at death, the odds of reaching CDR ≥1 at the last visit were lower in the ADV subjects compared to the pAD subjects. Conclusions: The mean rate of functional and cognitive decline among ADV subjects was slower than among either pAD or ADLBD patients. Vascular pathology did not increase the odds of attaining CDR ≥1 when occurring with AD in this national cohort.

scholarly journals Cognition at Each Stage of Lewy Body Disease with Co-occurring Alzheimer’s Disease Pathology

2021 ◽  
Vol 80 (3) ◽  
pp. 1243-1256
Author(s):  
Sephira G. Ryman ◽  
Maya Yutsis ◽  
Lu Tian ◽  
Victor W. Henderson ◽  
Thomas J. Montine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Cognitive Domain ◽  
Data Set ◽  
Pathologic Stage ◽  
Cortical Regions ◽  
The Impact

Background: Alzheimer’s disease neuropathologic change (ADNC) may contribute to dementia in patients with Lewy body disease (LBD) pathology. Objective: To examine how co-occurring ADNC impacts domain specific cognitive impairments at each pathologic stage (brainstem, limbic, cerebral cortical) of LBD. Methods: 2,433 participants with antemortem longitudinal neuropsychological assessment and postmortem neuropathological assessment from the National Alzheimer’s Coordinating Center’s Uniform Data Set were characterized based on the evaluation of ADNC and LBD. Longitudinal mixed-models were used to derive measures of cumulative cognitive deficit for each cognitive domain at each pathologic stage of LBD (brainstem, limbic, and cerebral cortical). Results: 111 participants with a pathologic diagnosis of LBD, 741 participants with combined LBD and ADNC, 1,357 participants with ADNC only, and 224 with no pathology (healthy controls) were included in the analyses. In the executive/visuospatial domain, combined LBD and ADNC showed worse deficits than LBD only when Lewy bodies were confined to the brainstem, but no difference when Lewy bodies extended to the limbic or cerebral cortical regions. The cerebral cortical LBD only group exhibited greater executive/visuospatial deficits than the ADNC only group. By contrast, the ADNC only group and the combined pathology group both demonstrated significantly greater cumulative memory deficits relative to Lewy body disease only, regardless of stage. Conclusion: The impact of co-occurring ADNC on antemortem cumulative cognitive deficits varies not only by domain but also on the pathological stage of Lewy bodies. Our findings stress the cognitive impact of different patterns of neuropathological progression in Lewy body diseases.

scholarly journals Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies

2020 ◽  
pp. 1-7
Author(s):  
Gemma Roberts ◽  
Paul C. Donaghy ◽  
Jim Lloyd ◽  
Rory Durcan ◽  
George Petrides ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diagnostic Accuracy ◽  
Lewy Body ◽  
Photon Emission ◽  
Lewy Bodies ◽  
Positive Likelihood Ratio ◽  
Lewy Body Disease

Background Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. Aims To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. Method We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. Results At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3. Conclusions It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.

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