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Diagnosis, Classification and Natural History of Degenerative Dementias

Published online by Cambridge University Press:  02 December 2014

H. Feldman
Affiliation:
Division of Neurology, UBC Hospital, Vancouver Canada
A. Kertesz
Affiliation:
Department, of Clinical Neurological Sciences, St. Joseph's Health Centre, London ON Canada
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Abstract

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The release of the first approved medications for the treatment of Alzheimer’s disease in Canada has highlighted the renewed need and importance of diagnostic accuracy and understanding of the spectrum of the dementias. The epidemiological scope of the problem of dementia in Canada including risk factors, caregiving patterns and costs of care have been well-characterized through the Canadian Study of Health and Aging (CSHA 1991-1996) with some of the key findings reviewed here. Beyond Alzheimer’s disease the phenotypes and genotypes of the other degenerative dementias have been emerging with proposed operational diagnostic criteria that should facilitate their recognition in clinical practice. This paper reviews the clinical phenotypes of the most common causes of dementia with a proposed classification scheme and with discussion of their relevance from a differential treatment standpoint. This paper served as a background document for the working group of the Consensus Conference on Dementia (C3D) in February 1998 and has been revised subsequently for this publication.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2001

References

REFERENCES

1. Morris, JC, McKeel, DW, Fulling, K, Torack, RM, Berg, L. Validation of clinical diagnostic criteria for Alzheimer’s disease. Ann Neurol 1988;24:1722.CrossRefGoogle ScholarPubMed
2. Tierney, MC, Fisher, RH, Lewis, AJ, et al. The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease: a clinicopathologic study of 57 cases. Neurology 1988;38:359364.CrossRefGoogle ScholarPubMed
3. APA (American Psychiatric Association). Diagnostic and Statistical Manual of Mental Disorders. Third, revised Ed. Washington, DC: American Psychiatric Association, 1987 Google Scholar
4. A PA (American Psychiatric Association). Diagnostic and Statistical Manual of Mental Disorders. Fourth Ed. Washington, DC: American Psychiatric Association, 1994 Google Scholar
5. World Health Organization. ICD-10: International statistical classification of diseases and related health problems: Based on recommendations of the Tenth Revision Conference, 1989 and adopted by the Forty-third World Health Assembly. 1992;10th revision edition:(Abstract).Google Scholar
6. Roth, M, Tym, E, Mountjoy, CQ, et al. CAMDEX – A standardized instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149:698709.CrossRefGoogle Scholar
7. Cummings, JL, Benson, DF. Dementia: definition, prevalence, classification, and approach to diagnosis. In: Anonymous Dementia: A Clinical Approach. 2nd Ed. Stoneham, MA: Butterworth-Heinemann, 1992:117.Google Scholar
8. Erkinjuntti, T, Ostbye, T, Steenhuis, R, Hachinski, V. The effect of different diagnostic criteria on the prevalence of dementia. N Engl J Med 1997;337:16671674.CrossRefGoogle ScholarPubMed
9. Verhey, FRJ, Lodder, J, Rozendaal, N, Jolles, J. Comparison of seven sets of criteria used for the diagnosis of vascular dementia. Neuroepidemiology 1996;15:166172.CrossRefGoogle ScholarPubMed
10. Canadian Study of Health and Aging Working Group. Canadian Study of Health and Aging: study methods and prevalence of dementia. Can Med Assoc J 1994;150:899913.Google Scholar
11. Launer, LJ, Hofman, A. Studies on the incidence of dementia: the European perspective [review]. Neuroepidemiology 1992;11:127134.CrossRefGoogle ScholarPubMed
12. McKhann, G, Drachman, DA, Folstein, M, et al. Clinical diagnosis of Alzheimer’s disease – report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984;34:939944.CrossRefGoogle ScholarPubMed
13. Boller, F, Lopez, OL, Moossy, J. Diagnosis of dementia: clinicopathologic correlations. Neurology 1989;39:7679.CrossRefGoogle ScholarPubMed
14. Mayeux, R, Saunders, AM, Shea, S, et al. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. N Engl J Med 1998;338:506511.CrossRefGoogle ScholarPubMed
15. Buschke, H. Cued recall in amnesia. J Clin Neuropsych 1984;6:433440.CrossRefGoogle ScholarPubMed
16. Blacker, D, Albert, MS, Bassett, SS, et al. Reliability and validity of NINCDS-ADRDAcriteria for Alzheimer’s disease. Arch Neurol 1994;51:11981204.CrossRefGoogle ScholarPubMed
17. Lund and Manchester Groups. Clinical and neuropathological criteria for frontotemporal dementia [review]. J Neurol Neurosurg Psychiatry 1994;57(4):416418.CrossRefGoogle Scholar
18. Kertesz, A, Davidson, W, Fox, H. Frontal behavioral inventory:diagnostic criteria for frontal lobe dementia. Can J Neurol Sci 1997;24:2936.CrossRefGoogle ScholarPubMed
19. Roman, GC, Tatemichi, TK, Erkinjuntti, T, et al. Vascular dementia:diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250260.CrossRefGoogle ScholarPubMed
20. Chui, HC, Victoroff, JI, Margolin, D, et al. Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s Disease Diagnostic and Treatment Centers. Neurology 1992;42:473480.CrossRefGoogle ScholarPubMed
21. McKeith, IG, Galasko, D, Kosaka, K, et al. Consensus guidelines for the clinical and pathological diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47:11131124.CrossRefGoogle Scholar
22. Litvan, I, Agid, Y, Goetz, C, et al. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997;48:119125.CrossRefGoogle ScholarPubMed
23. Miller, BL, Ikonte, C, Ponton, M, et al. A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations. Neurology 1997;48:937942.CrossRefGoogle ScholarPubMed
24. Amar, K, Wilcock, GK, Scott, M. The diagnosis of vascular dementiain the light of the new criteria. Age Ageing 1996;25:5155.CrossRefGoogle Scholar
25. Gold, G, Giannakopoulos, P, Montes-Paixao, C Jr, et al. Sensitivity and specificity of newly proposed clinical criteria for possible vascular dementia. Neurology 1997;49:690694.CrossRefGoogle ScholarPubMed
26. Mega, MS, Masterman, DL, Benson, DF, et al. Dementia with Lewy bodies: reliability and validity of clinical and pathologic criteria. Neurology 1996;47:14031409.CrossRefGoogle ScholarPubMed
27. McKeith, IG, Perry, EK, Perry, RH. Report of the second dementia with Lewy body international workshop. Neurology 1999;53:902905.CrossRefGoogle ScholarPubMed
28. McKeith, IG, Ayre, GA. Consensus criteria for the clinical diagnosis of dementia with Lewy bodies. In: Iqbal, K, Winblad, B, Nishimura, T, Takeda, M, Wisniewski, HM, eds. Alzheimer’s Disease: Biology, Diagnosis and Therapeutics. Chichester: John Wiley & Sons Ltd, 1997:167177.Google Scholar
29. McKeith, IG, Perry, RH, Fairburn, AF, Jabeen, S, Perry, EK. Operational criteria for senile dementia of Lewy body type. Psychol Med 1992;22:911922.CrossRefGoogle ScholarPubMed
30. Hansen, L, Salmon, D, Galasko, D, et al. The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology 1990;40:18.CrossRefGoogle ScholarPubMed
31. Byrne, EJ, Lennox, G, Lowe, J, Godwin-Austen, RB. Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry 1989;52:709717.CrossRefGoogle ScholarPubMed
32. Ballard, C, McKeith, I, Harrison, R, et al. A detailed phenomenological comparison of complex visual hallucinations in dementia with Lewy bodies and Alzheimer’s disease. Int Psychogeriatr 1997;9:381388.CrossRefGoogle ScholarPubMed
33. Lippa, CF, Smith, TW, Perry, E. Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology. J Neural Transm 1999;106:525535.CrossRefGoogle ScholarPubMed
34. Perry, EK, Haroutunian, V, Davis, KL, et al. Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer’s disease. Neuroreport 1994;5:747749.CrossRefGoogle ScholarPubMed
35. Dickson, DW, Davies, P, Mayeux, R, et al. Diffuse Lewy body disease. Neuropathological and biochemical studies of six patients. Acta Neuropathol (Berl.) 1987;75:815.CrossRefGoogle ScholarPubMed
36. McKeith, IG, Fairbairn, A, Perry, RH, Thompson, P, Perry, E. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ 1992;305:673678.CrossRefGoogle ScholarPubMed
37. Shea, C, MacKnight, C, Rockwood, K. Donepezil for treatment of dementia with Lewy bodies: a case series of nine patients. Int Psychogeriatr 1998;10:229238.CrossRefGoogle ScholarPubMed
38. McKeith, I, Del-Ser, T, Anand, R, et al. Rivastigmine provides symptomatic benefit in dementia with Lewy bodies: Findings from a placebo-controlled international multicenter study. Neurology 2000;54:A450(Abstract)Google Scholar
39. Holmes, C, Cairns, N, Lantos, P, Mann, A. Validity of current clinical criteria for Alzheimer’s disease, vascular dementia and dementia with Lewy bodies. Br J Psychiatry 1999;174:4550.CrossRefGoogle ScholarPubMed
40. Barber, R, Scheltens, P, Gholkar, A, et al. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer’s disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry 1999;67:6672.CrossRefGoogle ScholarPubMed
41. Mirra, SS, Gearing, M, Heyman, A. CERAD guide to the neuropathological assessment of Alzheimer’s disease and other dementias. For information contact: Albert Heyman MD, Box 3203 Duke University Medical Center, Durham NC 27710 USA. 1994.Google Scholar
42. Hansen, LA, Samuel, W. Criteria for Alzheimer’s disease and the nosology of dementia with Lewy bodies. Neurology 1997;48:126132.CrossRefGoogle ScholarPubMed
43. Mirra, SS, Gearing, M, Nash, F. Neuropathological assessment of Alzheimer’s disease. Neurology 1997;49(suppl 3):S14–S16CrossRefGoogle ScholarPubMed
44. Knopman, DS, Mastri, AR, Frey, WH, Sung, JH, Rustan, T. Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 1990;40:251256.CrossRefGoogle ScholarPubMed
45. Kertesz, A, Hudson, L, Mackenzi, IRA, Munoz, DG. The pathology and nosology of primary progressive aphasia. Neurology 1994;44:20652072.CrossRefGoogle ScholarPubMed
46. Kertesz, A, Munoz, DG. Pick’s Disease and Pick Complex. New York:Wilem-Liss, 1998.Google ScholarPubMed
47. Mesulam, MM. Slowly progressive aphasia without generalized dementia. Ann Neurol 1982;11:592598.CrossRefGoogle ScholarPubMed
48. Frattali, CM, Grafman, J, Patronas, N, Makhlouf, F, Litvan, I. Language disturbances in corticobasal degeneration. Neurology 2000;54:990992.CrossRefGoogle ScholarPubMed
49. Cummings, JL, Litvan, I. Neuropsychiatric aspects of corticobasal degeneration. Adv Neurol 2000; 82:147152.Google ScholarPubMed
50. Foster, NL, Wilhelmsen, K, Sima, AA, et al. Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants. [Review]. Ann Neurol 1997;41:706715.CrossRefGoogle ScholarPubMed
51. Spillantini, MG, Goedert, M, Crowther, RA, et al. Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments. Proc Natl Acad Sci USA 1997;94(8):41134118.CrossRefGoogle ScholarPubMed
52. Cooper, PN, Jackson, M, Lennox, G, Lowe, J, Mann, DM. Tau, ubiquitin, and alpha B-crystallin immunohistochemistry define the principal causes of degenerative frontotemporal dementia. Arch Neurol 1995;52:10111015.CrossRefGoogle ScholarPubMed
53. Froelich, S, Basun, H, Forsell, C, et al. Mapping of a disease locus for familial rapidly progressive frontotemporal dementia to chromosome 17q12–21. Am J Med Gen 1997;74:380385.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
54. Bird, TD, Nochlin, D, Poorkaj, P, et al. A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L) [published erratum appears in Brain 1999 Jul;122(Pt 7):1398]. Brain 1999;122:741756.CrossRefGoogle Scholar
55. Kertesz, A, Orange, JB. Primary progressive aphasia – the future of neurolinguistic and biologic characterization. Brain Lang 2000; 71:116119.CrossRefGoogle ScholarPubMed
56. Gustafson, L. Clinical picture of frontal lobe degeneration of non-Alzheimer type. Dementia 1993;4:143148.Google ScholarPubMed
57. Erkinjuntti, T, Hachinski, VC. Rethinking Vascular Dementia. Cerebrovasc Dis 1993;3:323.CrossRefGoogle Scholar
58. Hachinski, VC, Lassen, NA, Marshal, J. Multi-infarct dementia: a cause of mental deterioration in the elderly. Lancet 1974;2:207210.CrossRefGoogle ScholarPubMed
59. Rockwood, K, Ebly, EM, Hachinski, VC, Hogan, D. Presence and treatment of vascular risk factors in patients with vascular cognitive impairment. Arch Neurol 1997;54:3339.CrossRefGoogle ScholarPubMed
60. Rockwood, K, Black, S, Gauthier, S, Feldman, H, Wentzel, C. Clinical and neuroimaging findings in mixed dementia. Research and Practice in Alzheimer’s Disease 2000, 3rd Ed. Google ScholarPubMed
61. Joutel, A, Corpechot, C, Ducros, A, et al. Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia. Ann NY Acad Sci 1997; 826:213217.CrossRefGoogle ScholarPubMed
62. Joutel, A, Vahedi, K, Corpechot, C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 1997;350:15111515.CrossRefGoogle ScholarPubMed
63. Snowdon, DA, Greiner, LH, Mortimer, JA, et al. Brain infarction and the clinical expression of Alzheimer’s disease: The nun study. JAMA 1997;277:813817.CrossRefGoogle ScholarPubMed
64. Erkinjuntti, T, Inzitari, D, Pantoni, L, et al. Limitations of clinical criteria for the diagnosis of vascular dementia in clinical trials. Is a focus on subcortical vascular dementia a solution? Ann NY Acad Sci 2000;903:262272.CrossRefGoogle ScholarPubMed
65. Erkinjuntti, T, Inzitari, D, Pantoni, L, et al. Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm 2000;59(Suppl):2330.Google ScholarPubMed
66. Tomlinson, BE, Blessed, G, Roth, M. Observations on the brains of demented old people. J Neurol Sci 1970;11:205 242.CrossRefGoogle ScholarPubMed
67. Statistics Canada. A portrait of seniors in Canada (89–519–XPE). 1996.Google Scholar
68. The Canadian Study of Health and Aging. The Canadian Study of Health and Aging: risk factors for Alzheimer’s disease in Canada. Neurology 1994;44:20732080.CrossRefGoogle Scholar
69. Ostbye, T, Crosse, E. Net economic costs of dementia in Canada. Can Med Assoc J 1994;151:14571464.Google ScholarPubMed
70. McDowell, I. The incidence of dementia in Canada: The Canadian Study of Health and Aging Working Group. Neurology 2000.Google Scholar
71. Lindsay, J, Hebert, R, Rockwood, K. The Canadian Study of Health and Aging: risk factors for vascular dementia. Stroke 1997;28:526530.CrossRefGoogle ScholarPubMed
72. van Duijn, CM, Stijnen, T, Hofman, A. Risk factors for Alzheimer’s disease: overview of the EURODEM collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 (Suppl 2):S4–S12.Google ScholarPubMed
73. van Duijn, CM, Clayton, D, Chandra, V, et al. Familial aggregation of Alzheimer’s disease and related disorders: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 (Suppl 2):S13–S20.Google Scholar
74. Rocca, WA, van Duijn, CM, Clayton, D, et al. Maternal age and Alzheimer’s disease: a collaborative re- analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 (Suppl 2):S21–S27.CrossRefGoogle ScholarPubMed
75. Mortimer, JA, van Duijn, CM, Chandra, V, et al. Head trauma as a risk factor for Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 (Suppl 2):S28–S35.CrossRefGoogle ScholarPubMed
76. Breteler, MMB, van Duijn, CM, Chandra, V, et al. Medical history and the risk of Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 (Suppl 2):S36–S42.CrossRefGoogle ScholarPubMed
77. Jorm, AF, van Duijn, CM, Chandra, V, et al. Psychiatric history and related exposures as risk factors for Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 Suppl 2:S43–S47.CrossRefGoogle ScholarPubMed
78. Graves, AB, van Duijn, CM, Chandra, V, et al. Alcohol and tobacco consumption as risk factors for Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 (Suppl2) :S48–S57.Google ScholarPubMed
79. Graves, AB, van Duijn, CM, Chandra, V, et al. Occupational exposures to solvents and lead as risk factors for Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20 Suppl 2:S58–S61.Google ScholarPubMed
80. van Duijn, CM, Hofman, A. Risk factors for Alzheimer’s disease: the EURODEM collaborative re-analysis of case-control studies. Neuroepidemiology 1992;11 (Suppl 1):106113.CrossRefGoogle ScholarPubMed
81. Orgogozo, JM, Dartigues, JF, Lafont, S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol 1997;153(3):185192.Google ScholarPubMed
82. McEwen, BS, Alves, SE, Bulloch, K, Weiland, NG. Ovarian steroids and the brain: implications for cognition and aging. Neurology 1997;48(Suppl 7):S8–S15.CrossRefGoogle ScholarPubMed
83. Ferreira, A, Caceres, A. Estrogen-enhanced neurite growth: evidence for a selective induction of Tau and stable microtubules. J Neurosci 1991;11(2):392400.CrossRefGoogle ScholarPubMed
84. Warren, SG, Humphreys, AG, Juraska, JM, Greenough, WT. LTP varies across the estrous cycle: enhanced synaptic plasticity in proestrus rats. Brain Res 1995;703(1–2):2630.CrossRefGoogle ScholarPubMed
85. Birge, SJ. The role of estrogen deficiency in the aging central nervous system. In: Lobo, RA, Ed. Treatment of the postmenopausal woman: basic and clinical aspects. New York: Raven Press, 1994:153157.Google Scholar
86. Henderson, VW, Paganini-Hill, A, Emanuel, CK, Dunn, ME, Buckwalter, JG. Estrogen replacement therapy in older women. Arch Neurol 1994;51:896900.CrossRefGoogle ScholarPubMed
87. Paganini-Hill, A, Henderson, VW. Estrogen deficiency and risk of Alzheimer’s disease in women. Am J Epidemiol 1994;140:256261.CrossRefGoogle ScholarPubMed
88. Kawas, C, Resnick, S, Morrison, A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology 1997;48:15171521.CrossRefGoogle ScholarPubMed
89. Tang, MX, Jacobs, D, Stern, Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996;348:429432.CrossRefGoogle ScholarPubMed
90. Thal, LJ, Carta, A, Doody, R, et al. Prevention protocols for Alzheimer’s disease. Alzheimer Dis Assoc Disord 1997;11 (Supp 3) :4649.Google Scholar
91. Corder, EH, Saunders, AM, Strittmatter, WJ, et al. Gene dose of apoliprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993;261:921923.CrossRefGoogle Scholar
92. National Institute on Aging, Alzheimer’s Association Working Group. Apolipoprotein E genotyping in Alzheimer’s disease. Lancet 1996;347:10911095.CrossRefGoogle Scholar
93. Mayeux, R, Stern, Y, Ottman, R, et al. The apolipoprotein epsilon 4 allele in patients with Alzheimer’s disease. Ann Neurol 1993;34:752754.CrossRefGoogle ScholarPubMed
94. Lucotte, G, David, F, Visvikis, S, et al. Apolipoprotein E-epsilon 4 allele and Alzheimer’s disease. Lancet 1993;342:1309.Google ScholarPubMed
95. Nalbantoglu, J, Gilfix, BM, Bertrand, P, et al. Predictive value of apolipoprotein E genotyping in Alzheimer’s disease: results of an autopsy series and an analysis of several combined studies. Ann Neurol 1994;36:889895.CrossRefGoogle Scholar
96. Myers, RH, Schaefer, EJ, Wilson, PWF, et al. Apolipoprotien E e4 association with dementia in a population-based study: The Framingham Study. Neurology 1996;46:673677.CrossRefGoogle Scholar
97. Rockwood, K. Lessons from mixed dementia [editorial]. Int Psychogeriatr 1997;9:245249.CrossRefGoogle ScholarPubMed
98. Skoog, I. The relationship between blood pressure and dementia: a review. Biomed Pharmacother 1997;51:367375.CrossRefGoogle ScholarPubMed
99. Meyer, JS, McClintic, KL, Rogers, RL, Sims, P, Mortel, KF. Aetiological considerations and risk factors for multi-infarct dementia. J Neurol Neurosurg Psychiatry 1988;51:14891497.CrossRefGoogle ScholarPubMed
100. Berlinger, WG, Potter, JF. Low Body Mass Index in demented outpatients. J Am Geriatr Soc 1991;39:973978.CrossRefGoogle ScholarPubMed
101. Staessen, JA, Fagard, R, Thijs, L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997;350:757764.CrossRefGoogle ScholarPubMed
102. Maxwell, CJ, Hogan, DB, Ebly, EM. Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging. 1999;161 (5):501506.Google ScholarPubMed
103. Galasko, D, Edland, SD, Morris, JC, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part XI. Clinical milestones in patients with Alzheimer’s disease followed over 3 years. Neurology 1995;45: 14511455.CrossRefGoogle Scholar
104. Reisberg, B, Ferris, SH, de Leon, MJ, Crook, T. The Global Deterioration Scale (GDS). Psychopharmacol Bull 1988;24(4): 661663.Google ScholarPubMed
105. Feldman, H, Schulzer, M, Wang, S, Tuokko, H, Beattie BL. The Functional Rating Scale in Alzheimer’s disease assessment: a longitudinal study. Research Advances in Alzheimer’s Disease and Related Disorders 1995;235241.Google Scholar
106. Scheltens, P, Leys, D, Barkhof, F, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1992;55:967972.CrossRefGoogle ScholarPubMed
107. Kennard, ML, Feldman, H, Yamada, T, Jefferies WA. Serum levels of the iron binding protein, p97 are elevated in Alzheimer’s disease. Nat Med 1996;2(11):12301235.CrossRefGoogle ScholarPubMed
108. Licastro, F, Davis, LJ, Polazzi, E, Rossi, S, Cucinotta, D. Serological alpha 1-antichymotrypsin in patients with probable senile dementia of Alzheimer type: a short-term longitudinal study. Alzheimer Dis Assoc Disord 1996;10:192196.CrossRefGoogle ScholarPubMed
109. Laakso, MP, Partanen, K, Riekkinen, P, et al. Hippocampal volumes in Alzheimer’s disease, Parkinson’s disease with and without dementia, and in vascular dementia: an MRI study. Neurology 1996;46:678681.CrossRefGoogle ScholarPubMed
110. Seubert, P, Motter, R, Schenk, D, et al. Elevation of CSF tau in early stage Alzheimer’s disease. Neurology 1997;46:A161(Abstract).Google Scholar
111. Galasko, D, Seubert, P, Motter, R, et al. CSF levels of A-beta 432 and tau as aids to diagnosing Alzheimer’s disease. Neurology 1997;48:A379(Abstract).Google Scholar
112. Reisberg, B. Functional Assessment Staging (FAST). Psychopharmacol Bull 1988;24(4):653659.Google ScholarPubMed
113. Reisberg, B, Ferris, SH, Franssen, EH, et al. Mortality and temporal course of probable Alzheimer’s disease: a 5-year prospective study. Int Psychogeriatr 1996;8:291311.CrossRefGoogle ScholarPubMed
114. Reisberg, B, Sclan, SG, Franssen, E, Kluger, A, Ferris, SH. Dementia staging in chronic care populations. [Review]. Alzheimer Dis Assoc Disord 1994;8 (Suppl 1):S188–S205Google ScholarPubMed
115. Mann, UM, Mohr, E, Gearing, M, Chase, TN. Heterogeneity in Alzheimer’s disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles. J Neurol Neurosurg Psychiatry 1992;55:956959.CrossRefGoogle ScholarPubMed
116. Boller, F, Becker, JT, Holland, AL, Forbes, MM, Hood, PC. Predictors of decline in Alzheimer’s Disease. Cortex 1991;27:917.CrossRefGoogle ScholarPubMed
117. Yesavage, JA, Brooks, JO, Taylor, J, Tinkelberg, J. Development of aphasia, apraxia, and agnosia and decline in Alzheimer’s disease. Am J Psychiatry 1993;150:742747.Google ScholarPubMed
118. Stern, Y, Mayeux, R, Sano, M, Hauser, WA, Bush, T. Predictors of disease course in patients with probable Alzheimer’s disease. Neurology 1987;37:16491653.CrossRefGoogle ScholarPubMed
119. Stern, Y, Albert, M, Brandt, J, et al. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer’s disease: prospective analyses from the Predictors Study. Neurology 1994;44:23002307.CrossRefGoogle ScholarPubMed
120. Jacobs, D, Sano, M, Marder, K, et al. Age at onset of Alzheimer’s disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology 1994;44:12151220.CrossRefGoogle ScholarPubMed