Mixed Pathologies and Neural Reserve: Implications of Complexity for Alzheimer Disease Drug Discovery

Overview

Journal PLoS Med

Specialty General Medicine

Date 2017 Mar 15

PMID 28291788

Citations 37

Authors

David A Bennett

Affiliations

Soon will be listed here.

Abstract

In a Perspective, David Bennett makes a case for neural reserve to be considered as a therapeutic endpoint in clinical trials for dementia.

Citing Articles

Moderate-to-Vigorous Physical Activity at any Dose Reduces All-Cause Dementia Risk Regardless of Frailty Status.

Wanigatunga A, Dong Y, Jin M, Leroux A, Cui E, Zhou X J Am Med Dir Assoc. 2025; 26(3):105456.

PMID: 39826907 PMC: 11890932. DOI: 10.1016/j.jamda.2024.105456.

Exploring temporal and sex-linked dysregulation in Alzheimer disease phosphoproteome.

Yilmaz S, Lopes F, Schlatzer D, Wang R, Qi X, Koyuturk M iScience. 2024; 27(10):110941.

PMID: 39391719 PMC: 11465087. DOI: 10.1016/j.isci.2024.110941.

Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.

Kotredes K, Pandey R, Persohn S, Elderidge K, Burton C, Miner E Alzheimers Dement. 2024; 20(6):4126-4146.

PMID: 38735056 PMC: 11180851. DOI: 10.1002/alz.13828.

Brain-age estimation with a low-cost EEG-headset: effectiveness and implications for large-scale screening and brain optimization.

Kounios J, Fleck J, Zhang F, Oh Y Front Neuroergon. 2024; 5:1340732.

PMID: 38721435 PMC: 11077564. DOI: 10.3389/fnrgo.2024.1340732.

Assessment of neurovascular uncoupling: APOE status is a key driver of early metabolic and vascular dysfunction.

Onos K, Lin P, Pandey R, Persohn S, Burton C, Miner E Alzheimers Dement. 2024; 20(7):4951-4969.

PMID: 38713704 PMC: 11247674. DOI: 10.1002/alz.13842.

References

Grinberg L, Nitrini R, Suemoto C, Ferretti-Rebustini R, Leite R, Farfel J . Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clinics (Sao Paulo). 2013; 68(8):1140-5. PMC: 3752642. DOI: 10.6061/clinics/2013(08)13. View

Sonnen J, Santa Cruz K, Hemmy L, Woltjer R, Leverenz J, Montine K . Ecology of the aging human brain. Arch Neurol. 2011; 68(8):1049-56. PMC: 3218566. DOI: 10.1001/archneurol.2011.157. View

Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P . Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol. 1988; 23(2):138-44. DOI: 10.1002/ana.410230206. View

del Ser T, Hachinski V, Merskey H, Munoz D . An autopsy-verified study of the effect of education on degenerative dementia. Brain. 1999; 122 ( Pt 12):2309-19. DOI: 10.1093/brain/122.12.2309. View

Stephan B, Matthews F, Ma B, Muniz G, Hunter S, Davis D . Alzheimer and vascular neuropathological changes associated with different cognitive States in a non-demented sample. J Alzheimers Dis. 2012; 29(2):309-18. PMC: 3975483. DOI: 10.3233/JAD-2011-110518. View

Farfel J, Nitrini R, Suemoto C, Grinberg L, Ferretti R, Leite R . Very low levels of education and cognitive reserve: a clinicopathologic study. Neurology. 2013; 81(7):650-7. PMC: 3775692. DOI: 10.1212/WNL.0b013e3182a08f1b. View

Dodge H, Zhu J, Woltjer R, Nelson P, Bennett D, Cairns N . Risk of incident clinical diagnosis of Alzheimer's disease-type dementia attributable to pathology-confirmed vascular disease. Alzheimers Dement. 2016; 13(6):613-623. PMC: 5466467. DOI: 10.1016/j.jalz.2016.11.003. View

White L, Edland S, Hemmy L, Montine K, Zarow C, Sonnen J . Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies. Neurology. 2016; 86(11):1000-8. PMC: 4799714. DOI: 10.1212/WNL.0000000000002480. View

Wilson R, Nag S, Boyle P, Hizel L, Yu L, Buchman A . Neural reserve, neuronal density in the locus ceruleus, and cognitive decline. Neurology. 2013; 80(13):1202-8. PMC: 3691778. DOI: 10.1212/WNL.0b013e3182897103. View

10.

James B, Wilson R, Boyle P, Trojanowski J, Bennett D, Schneider J . TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia. Brain. 2016; 139(11):2983-2993. PMC: 5091047. DOI: 10.1093/brain/aww224. View

11.

Brookmeyer R, Kawas C, Abdallah N, Paganini-Hill A, Kim R, Corrada M . Impact of interventions to reduce Alzheimer's disease pathology on the prevalence of dementia in the oldest-old. Alzheimers Dement. 2016; 12(3):225-32. PMC: 4808364. DOI: 10.1016/j.jalz.2016.01.004. View

12.

Montine T, Sonnen J, Montine K, Crane P, Larson E . Adult Changes in Thought study: dementia is an individually varying convergent syndrome with prevalent clinically silent diseases that may be modified by some commonly used therapeutics. Curr Alzheimer Res. 2012; 9(6):718-23. PMC: 3409333. DOI: 10.2174/156720512801322555. View

13.

Jack Jr C, Wiste H, Weigand S, Knopman D, Vemuri P, Mielke M . Age, Sex, and APOE ε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span. JAMA Neurol. 2015; 72(5):511-9. PMC: 4428984. DOI: 10.1001/jamaneurol.2014.4821. View

14.

Yu L, Boyle P, Segawa E, Leurgans S, Schneider J, Wilson R . Residual decline in cognition after adjustment for common neuropathologic conditions. Neuropsychology. 2014; 29(3):335-43. PMC: 4420708. DOI: 10.1037/neu0000159. View

15.

Schneider J, Arvanitakis Z, Leurgans S, Bennett D . The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol. 2009; 66(2):200-8. PMC: 2812870. DOI: 10.1002/ana.21706. View

16.

Brayne C, Ince P, Keage H, McKeith I, Matthews F, Polvikoski T . Education, the brain and dementia: neuroprotection or compensation?. Brain. 2010; 133(Pt 8):2210-6. DOI: 10.1093/brain/awq185. View

17.

Honda H, Sasaki K, Hamasaki H, Shijo M, Koyama S, Ohara T . Trends in autopsy-verified dementia prevalence over 29 years of the Hisayama study. Neuropathology. 2016; 36(4):383-7. DOI: 10.1111/neup.12298. View

18.

Norton S, Matthews F, Barnes D, Yaffe K, Brayne C . Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 2014; 13(8):788-94. DOI: 10.1016/S1474-4422(14)70136-X. View

19.

Valenzuela M, Matthews F, Brayne C, Ince P, Halliday G, Kril J . Multiple biological pathways link cognitive lifestyle to protection from dementia. Biol Psychiatry. 2011; 71(9):783-91. DOI: 10.1016/j.biopsych.2011.07.036. View

20.

Cummings J, Morstorf T, Zhong K . Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014; 6(4):37. PMC: 4095696. DOI: 10.1186/alzrt269. View