Semin Neurol 2019; 39(02): 153-166
DOI: 10.1055/s-0039-1683445
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

An Overview of Primary Dementias as Clinicopathological Entities

Arash Salardini
1   Department of Neurology, Yale School of Medicine, New Haven, Connecticut
› Author Affiliations
Further Information

Publication History

Publication Date:
29 March 2019 (online)

Abstract

Dementia is a state of cognitive dysfunction which leads to functional decline. It is a syndrome caused by several medical and neurological causes, but most cases of dementia are due to “primary dementias.” Primary dementias are neurological diseases whose manifestations are predominantly cognitive. Most primary dementias are caused by neurodegenerative proteinopathies where an accumulation of misfolded proteins leads to neuronal loss, neuroinflammation and glial reaction. Each proteinopathy is characterized by the type of protein implicated in its pathophysiology. Neurodegenerative dementias include the most prevalent cause of dementia—Alzheimer's disease—as well as Lewy body dementia, Parkinson's disease dementia, frontotemporal dementias, and prion diseases. Vascular dementia, especially small vessel disease, though not a neurodegenerative condition, is often grouped together with primary dementias. Each type of proteinopathy, characterized by the location and nature of misfolded protein accumulation, may correspond to a particular clinical phenotype. The correspondence between pathologies and clinical phenotypes is not exclusive, and there is a large degree of overlap. Although in the research setting the clinicopathological construct is on the wane, in the clinic it is the most practical way of approaching primary dementias. In this article, we introduce the clinicopathological construct, the understanding of which will form the basis of the other articles in this volume.

 
  • References

  • 1 LoGiudice D, Watson DLR. Dementia in older people: an update. Int Med J 2014; 44 (11) 1066-1073
  • 2 Sacuiu SF. Dementias. Handb Clin Neurol 2016; 138: 123-151
  • 3 Hogan DB, Fiest KM, Roberts JI. , et al. The prevalence and incidence of dementia with Lewy bodies: a systematic review. Can J Neurol Sci 2016; 43 (1, Suppl 1): S83-S95
  • 4 GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol 2018; 16 (11) 877-897
  • 5 McKhann GM, Knopman DS, Chertkow H. , et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7 (03) 263-269
  • 6 Albert MS, DeKosky ST, Dickson D. , et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7 (03) 270-279
  • 7 Geschwind MD. Rapidly progressive dementia. Continuum (Minneap Minn) 2016; 22 (2 Dementia): 510-537
  • 8 National Cancer Institute. Definition of biomarker - NCI dictionary of cancer terms. 2011 . Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biomarker . Accessed February 6, 2019
  • 9 Sachdev PS, Blacker D, Blazer DG. , et al. Classifying neurocognitive disorders: the DSM-5 approach. Nat Rev Neurol 2014; 10 (11) 634-642
  • 10 Schinka JA, Loewenstein DA, Raj A. , et al. Defining mild cognitive impairment: impact of varying decision criteria on neuropsychological diagnostic frequencies and correlates. Am J Geriatr Psychiatry 2010; 18 (08) 684-691
  • 11 Desai AK, Grossberg GT, Sheth DN. Activities of daily living in patients with dementia: clinical relevance, methods of assessment and effects of treatment. CNS Drugs 2004; 18 (13) 853-875
  • 12 Mlinac ME, Feng MC. Assessment of activities of daily living, self-care, and independence. Arch Clin Neuropsychol 2016; 31 (06) 506-516
  • 13 Petersen RC. Mild cognitive impairment. Continuum (Minneap Minn) 2016; 22 (2 Dementia): 404-418
  • 14 Eliassen CF, Reinvang I, Selnes P, Grambaite R, Fladby T, Hessen E. Biomarkers in subtypes of mild cognitive impairment and subjective cognitive decline. Brain Behav 2017; 7 (09) e00776
  • 15 Roberts R, Knopman DS. Classification and epidemiology of MCI. Clin Geriatr Med 2013; 29 (04) 753-772
  • 16 Cykowski MD, Powell SZ, Schulz PE. , et al. Hippocampal sclerosis in older patients: practical examples and guidance with a focus on cerebral age-related TDP-43 with sclerosis. Arch Pathol Lab Med 2017; 141 (08) 1113-1126
  • 17 Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004; 10 (Suppl): S10-S17
  • 18 Elahi FM, Miller BL. A clinicopathological approach to the diagnosis of dementia. Nat Rev Neurol 2017; 13 (08) 457-476
  • 19 Jack Jr CR, Bennett DA, Blennow K. , et al; Contributors. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018; 14 (04) 535-562
  • 20 Draper B, Withall A. Young onset dementia. Int Med J 2016; 46 (07) 779-786
  • 21 Kuruppu DK, Matthews BR. Young-onset dementia. Semin Neurol 2013; 33 (04) 365-385
  • 22 Salardini A, Biller J. . The Hospital Neurology Book. New York, NY: McGraw-Hill Education; 2016
  • 23 Hoenig MC, Bischof GN, Seemiller J. , et al. Networks of tau distribution in Alzheimer's disease. Brain 2018; 141 (02) 568-581
  • 24 Grand JH, Caspar S, Macdonald SW. Clinical features and multidisciplinary approaches to dementia care. J Multidiscip Healthc 2011; 4: 125-147
  • 25 Morris JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr 1997; 9 (Suppl. 01) 173-176 , discussion 177–178
  • 26 Perl DP. Neuropathology of Alzheimer's disease. Mt Sinai J Med 2010; 77 (01) 32-42
  • 27 Lam B, Masellis M, Freedman M, Stuss DT, Black SE. Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome. Alzheimers Res Ther 2013; 5 (01) 1
  • 28 Carmona S, Hardy J, Guerreiro R. The genetic landscape of Alzheimer disease. Handb Clin Neurol 2018; 148: 395-408
  • 29 Crous-Bou M, Minguillón C, Gramunt N, Molinuevo JL. Alzheimer's disease prevention: from risk factors to early intervention. Alzheimers Res Ther 2017; 9 (01) 71
  • 30 Chouraki V, Reitz C, Maury F. , et al; International Genomics of Alzheimer's Project. Evaluation of a genetic risk score to improve risk prediction for Alzheimer's disease. J Alzheimers Dis 2016; 53 (03) 921-932
  • 31 Jack CR, Knopman DS, Jagust WJ. , et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013; 12 (02) 207-216
  • 32 Janelidze S, Zetterberg H, Mattsson N. , et al; Swedish BioFINDER study group. CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 2016; 3 (03) 154-165
  • 33 Palmqvist S, Zetterberg H, Mattsson N. , et al; Alzheimer's Disease Neuroimaging Initiative; Swedish BioFINDER Study Group. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology 2015; 85 (14) 1240-1249
  • 34 Mattsson N, Schöll M, Strandberg O. , et al. 18F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer's disease. EMBO Mol Med 2017; 9 (09) 1212-1223
  • 35 Harper L, Barkhof F, Fox NC, Schott JM. Using visual rating to diagnose dementia: a critical evaluation of MRI atrophy scales. J Neurol Neurosurg Psychiatry 2015; 86 (11) 1225-1233
  • 36 Rice L, Bisdas S. The diagnostic value of FDG and amyloid PET in Alzheimer's disease-a systematic review. Eur J Radiol 2017; 94: 16-24
  • 37 Livingston G, Sommerlad A, Orgeta V. , et al. Dementia prevention, intervention, and care. Lancet 2017; 390 (10113): 2673-2734
  • 38 Mackenzie IR, Neumann M. Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. J Neurochem 2016; 138 (Suppl. 01) 54-70
  • 39 Mann DMA, Snowden JS. Frontotemporal lobar degeneration: pathogenesis, pathology and pathways to phenotype. Brain Pathol 2017; 27 (06) 723-736
  • 40 Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet 2015; 386 (10004): 1672-1682
  • 41 Ghosh S, Lippa CF. Clinical subtypes of frontotemporal dementia. Am J Alzheimers Dis Other Demen 2015; 30 (07) 653-661
  • 42 Pressman PS, Miller BL. Diagnosis and management of behavioral variant frontotemporal dementia. Biol Psychiatry 2014; 75 (07) 574-581
  • 43 Marshall CR, Hardy CJD, Volkmer A. , et al. Primary progressive aphasia: a clinical approach. J Neurol 2018; 265 (06) 1474-1490
  • 44 Lopez G, Bayulkem K, Hallett M. Progressive supranuclear palsy (PSP): Richardson syndrome and other PSP variants. Acta Neurol Scand 2016; 134 (04) 242-249
  • 45 Niccolini F, Wilson H, Hirschbichler S. , et al; Alzheimer's Disease Neuroimaging Initiative. Disease-related patterns of in vivo pathology in corticobasal syndrome. Eur J Nucl Med Mol Imaging 2018; 45 (13) 2413-2425
  • 46 Lillo P, Hodges JR. Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J Clin Neurosci 2009; 16 (09) 1131-1135
  • 47 Meeter LH, Kaat LD, Rohrer JD, van Swieten JC. Imaging and fluid biomarkers in frontotemporal dementia. Nat Rev Neurol 2017; 13 (07) 406-419
  • 48 Tsuboi Y, Uchikado H, Dickson DW. Neuropathology of Parkinson's disease dementia and dementia with Lewy bodies with reference to striatal pathology. Parkinsonism Relat Disord 2007; 13 (Suppl. 03) S221-S224
  • 49 Walker L, McAleese KE, Thomas AJ. , et al. Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes. Acta Neuropathol 2015; 129 (05) 729-748
  • 50 Gomperts SN. Lewy body dementias: dementia with Lewy bodies and Parkinson disease dementia. Continuum (Minneap Minn) 2016; 22 (2 Dementia): 435-463
  • 51 Vergouw LJM, van Steenoven I, van de Berg WDJ. , et al. An update on the genetics of dementia with Lewy bodies. Parkinsonism Relat Disord 2017; 43: 1-8
  • 52 McKeith IG, Boeve BF, Dickson DW. , et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 2017; 89 (01) 88-100
  • 53 O'Brien JT, Thomas A. Vascular dementia. Lancet 2015; 386 (10004): 1698-1706
  • 54 Kirshner HS, Bradshaw M. The inflammatory form of cerebral amyloid angiopathy or “cerebral amyloid angiopathy-related inflammation” (CAARI). Curr Neurol Neurosci Rep 2015; 15 (08) 54
  • 55 Croall ID, Lohner V, Moynihan B. , et al. Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies. Clin Sci (Lond) 2017; 131 (12) 1361-1373
  • 56 Sachdev P, Kalaria R, O'Brien J. , et al; Internationlal Society for Vascular Behavioral and Cognitive Disorders. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord 2014; 28 (03) 206-218
  • 57 Ikram MA, Bersano A, Manso-Calderón R. , et al. Genetics of vascular dementia – review from the ICVD working group. BMC Med 2017; 15 (01) 48
  • 58 Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol 2009; 8 (11) 1006-1018
  • 59 Rosenberg GA, Wallin A, Wardlaw JM. , et al. Consensus statement for diagnosis of subcortical small vessel disease. J Cereb Blood Flow Metab 2016; 36 (01) 6-25
  • 60 Ritchie DL, Ironside JW. Neuropathology of human prion diseases. Prog Mol Biol Transl Sci 2017; 150: 319-339
  • 61 Ironside JW, Ritchie DL, Head MW. Prion diseases. Handb Clin Neurol 2017; 145: 393-403
  • 62 Geschwind MD. Prion diseases. Continuum (Minneap Minn) 2015; 21 (6 Neuroinfectious Disease): 1612-1638