scholarly journals Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias

2014 ◽  
Vol 25 (4) ◽  
pp. 401-408 ◽  
Author(s):  
David R. Howlett ◽  
David Whitfield ◽  
Mary Johnson ◽  
Johannes Attems ◽  
John T. O'Brien ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Lewy Body ◽  
Multiple Pathology

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.

[P2-204]: RPT6, 20S α-6 AND α-3 PROTEASOME SUBUNIT LEVELS AND ASSOCIATION WITH COGNITIVE DECLINE IN ALZHEIMER's DISEASE AND LEWY BODY DEMENTIAS

2017 ◽  
Vol 13 (7S_Part_14) ◽  
pp. P684-P684
Author(s):  
Tibor Hortobagyi ◽  
Amani Alghamdi ◽  
David Whitfield ◽  
Julie Vallortigara ◽  
David Howlett ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Lewy Body ◽  
Proteasome Subunit

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 Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 108 ◽  
Author(s):  
Julie Vallortigara ◽  
Sindhoo Rangarajan ◽  
David Whitfield ◽  
Amani Alghamdi ◽  
David Howlett ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cognitive Decline ◽  
Lewy Body ◽  
Grey Matter ◽  
Psychiatric Symptoms ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Molecular Processes ◽  
Cortex Area ◽  
Synaptic Markers

Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer’s disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques - tangles) and for α-synuclein (Lewy bodies).Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex. On one hand, levels of Dynamin1 were significantly reduced, and correlated with a higher rate of cognitive decline observed in cases from three dementia groups. On the other hand, the fraction of phospho-CaMKII was decreased, and correlated with a high score of plaques and tangles in BA9. Interestingly, the correlation between the rate of cognitive decline and the level of Dynamin1 remained when the analysis was restricted to the PDD and DLB cases, highlighting an association of Dynamin1 with cognitive decline in people with Lewy Body dementia.

BuChE-K and APOE ϵ4 allele frequencies in Lewy body dementias, and influence of genotype and hyperhomocysteinemia on cognitive decline

2008 ◽  
Vol 24 (3) ◽  
pp. 392-400 ◽  
Author(s):  
Roger Lane ◽  
Yunsheng He ◽  
Christopher Morris ◽  
James B. Leverenz ◽  
Murat Emre ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Lewy Body ◽  
Allele Frequencies
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