Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship

Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer disease (AD). There is controversy regarding the use of current diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to cognitive impairment. Because AD is specific to humans, rigorous and comprehensiveclinicopathologic studies are necessary to test and refine hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but thepredictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration. We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy. There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD. For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function. We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.

[1]  F. Schmitt,et al.  Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer's disease and AD + DLB. , 2009, Journal of Alzheimer's disease : JAD.

[2]  W. Markesbery,et al.  Characterization of Japanese-American men with a single neocortical AD lesion type , 2008, Neurobiology of Aging.

[3]  C. Jack,et al.  MRI correlates of neurofibrillary tangle pathology at autopsy , 2008, Neurology.

[4]  Seth Love,et al.  Long-term effects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial , 2008, The Lancet.

[5]  Hyoung-Gon Lee,et al.  Alzheimer Disease Pathology As a Host Response , 2008, Journal of neuropathology and experimental neurology.

[6]  H. Braak,et al.  Invited Article: Nervous system pathology in sporadic Parkinson disease , 2008, Neurology.

[7]  T. Koepsell,et al.  Education, cognitive function, and severity of neuropathology in Alzheimer disease , 2008, Neurology.

[8]  D. Holtzman,et al.  Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease , 2008, Nature.

[9]  R. Mayeux,et al.  Alzheimer's disease: advances in trafficking , 2008, The Lancet Neurology.

[10]  R. Petersen,et al.  Mild Cognitive Impairment: An Overview , 2008, CNS Spectrums.

[11]  H. Braak,et al.  Neurofibrillary changes of the Alzheimer type in very elderly individuals: Neither inevitable nor benign Commentary on “No disease in the brain of a 115-year-old woman” , 2007, Neurobiology of Aging.

[12]  D. Graham,et al.  Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans , 2007, Experimental Neurology.

[13]  Peter T Nelson,et al.  Clinicopathologic Correlations in a Large Alzheimer Disease Center Autopsy Cohort: Neuritic Plaques and Neurofibrillary Tangles "Do Count" When Staging Disease Severity , 2007, Journal of neuropathology and experimental neurology.

[14]  C. Bouras,et al.  Identification of Alzheimer and vascular lesion thresholds for mixed dementia. , 2007, Brain : a journal of neurology.

[15]  S. Haneuse,et al.  Pathological correlates of dementia in a longitudinal, population‐based sample of aging , 2007, Annals of neurology.

[16]  D. Berlau,et al.  Dissociation of Neuropathologic Findings and Cognition: Case Report of an Apolipoprotein E ε2/ε2 Genotype , 2007 .

[17]  D. Bennett,et al.  Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons , 2007, Annals of neurology.

[18]  Joylee Wu,et al.  The National Alzheimer's Coordinating Center (NACC) Database: The Uniform Data Set , 2007, Alzheimer disease and associated disorders.

[19]  J. Schneider,et al.  Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration , 2007, Acta Neuropathologica.

[20]  K. Jellinger,et al.  Neuropathological evaluation of mixed dementia , 2007, Journal of the Neurological Sciences.

[21]  C. J. Rivara,et al.  Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm? , 2007, Journal of the Neurological Sciences.

[22]  J. Keller,et al.  RNA in Brain Disease: No Longer Just "The Messenger in the Middle" , 2007, Journal of neuropathology and experimental neurology.

[23]  D. Labarthe,et al.  Prevalence of stroke--United States, 2005. , 2007, MMWR. Morbidity and mortality weekly report.

[24]  F. Schmitt,et al.  Brain structural alterations before mild cognitive impairment , 2007, Neurology.

[25]  P. Hof,et al.  Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia , 2007, Neurology.

[26]  M. Mesulam,et al.  Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease , 2007, Neurobiology of Aging.

[27]  D. Berlau,et al.  Dissociation of neuropathologic findings and cognition: case report of an apolipoprotein E epsilon2/epsilon2 genotype. , 2007, Archives of neurology.

[28]  D. Dickson,et al.  Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration , 2006, Acta Neuropathologica.

[29]  J. Morris,et al.  Survival and mortality differences between dementia with Lewy bodies vs Alzheimer disease , 2006, Neurology.

[30]  T. Iwaki,et al.  Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle‐only dementia): The Hisayama study , 2006, Neuropathology : official journal of the Japanese Society of Neuropathology.

[31]  Chris Zarow,et al.  Cognitive impact of subcortical vascular and Alzheimer's disease pathology , 2006, Annals of neurology.

[32]  G. Livingston,et al.  Relationship of vascular risk to the progression of Alzheimer disease , 2006, Neurology.

[33]  P. S. St George-Hyslop,et al.  Characterization of the Kindred of Alois Alzheimer's Patient With Plaque-only Dementia , 2006, Alzheimer disease and associated disorders.

[34]  J. Schneider,et al.  Neuropathology of older persons without cognitive impairment from two community-based studies , 2006, Neurology.

[35]  E. Tangalos,et al.  Neuropathologic features of amnestic mild cognitive impairment. , 2006, Archives of neurology.

[36]  R. Petersen,et al.  Incidence and causes of nondegenerative nonvascular dementia: a population-based study. , 2006, Archives of neurology.

[37]  Yvette I. Sheline,et al.  Potential antecedent marker of Alzheimer disease , 2006 .

[38]  Charles D. Smith,et al.  Neuropathologic substrate of mild cognitive impairment. , 2006, Archives of neurology.

[39]  W. Markesbery,et al.  Recent Clinical-Pathologic Research on the Causes of Dementia in Late Life: Update From the Honolulu-Asia Aging Study , 2005, Journal of geriatric psychiatry and neurology.

[40]  Y. Stern,et al.  APOE related alterations in cerebral activation even at college age , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[41]  M. Chong,et al.  Preclinical Alzheimer's disease: diagnosis and prediction of progression , 2005, The Lancet Neurology.

[42]  Lars Bäckman,et al.  Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis. , 2005, Neuropsychology.

[43]  E B Larson,et al.  Cognitive differences in dementia patients with autopsy-verified AD, Lewy body pathology, or both , 2005, Neurology.

[44]  P. Zandi,et al.  A Population Study of Alzheimer’s Disease: Findings From the Cache County Study on Memory, Health, and Aging , 2005, Care Management Journals.

[45]  P. Hof,et al.  Cognitive Consequences of Thalamic, Basal Ganglia, and Deep White Matter Lacunes in Brain Aging and Dementia , 2005, Stroke.

[46]  J. Morris,et al.  Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study. , 2005, Archives of neurology.

[47]  K. Jellinger,et al.  Correlations between mental state and quantitative neuropathology in the Vienna Longitudinal Study on Dementia , 2005, European Archives of Psychiatry and Clinical Neuroscience.

[48]  Paul G. Ince,et al.  Vascular pathologies and cognition in a population-based cohort of elderly people , 2004, Journal of the Neurological Sciences.

[49]  Henry Rusinek,et al.  Magnetic resonance and PET studies in the early diagnosis of Alzheimer’s disease , 2004, Expert review of neurotherapeutics.

[50]  Dietmar Rudolf Thal,et al.  Neurodegeneration in normal brain aging and disease. , 2004, Science of aging knowledge environment : SAGE KE.

[51]  L A Hansen,et al.  The importance of neuritic plaques and tangles to the development and evolution of AD , 2004, Neurology.

[52]  M. Mesulam,et al.  Cholinergic nucleus basalis tauopathy emerges early in the aging‐MCI‐AD continuum , 2004, Annals of neurology.

[53]  L. Thal,et al.  Alzheimer disease without neocortical neurofibrillary tangles , 2004, Neurology.

[54]  D. Bennett,et al.  Decreases in soluble α-synuclein in frontal cortex correlate with cognitive decline in the elderly , 2004, Neuroscience Letters.

[55]  J. Trojanowski,et al.  More than just two peas in a pod: common amyloidogenic properties of tau and α-synuclein in neurodegenerative diseases , 2004, Trends in Neurosciences.

[56]  J. Schneider,et al.  Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. , 2004, Archives of neurology.

[57]  Michel Goedert,et al.  Tau protein and neurodegeneration. , 2004, Seminars in cell & developmental biology.

[58]  K. Jellinger.  Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies , 2004, Neurology.

[59]  H. Wiśniewski,et al.  Phagocytosis of β/A4 amyloid fibrils of the neuritic neocortical plaques , 2004, Acta Neuropathologica.

[60]  H. Mori,et al.  Curly fibers are tau-positive strands in the pre- and post-synaptic neurites, consisting of paired helical filaments: observations by the freeze-etch and replica method , 2004, Acta Neuropathologica.

[61]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[62]  Henry Rusinek,et al.  Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. , 2003, Radiology.

[63]  Keith A. Johnson,et al.  Neuropathology of Cognitively Normal Elderly , 2003, Journal of neuropathology and experimental neurology.

[64]  D. Bennett,et al.  Alzheimer disease in the US population: prevalence estimates using the 2000 census. , 2003, Archives of neurology.

[65]  K. Rockwood.  Mixed Dementia: Alzheimer's and Cerebrovascular Disease , 2003, International Psychogeriatrics.

[66]  D. Jeste,et al.  Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies , 2003, Neurology.

[67]  M. Mesulam,et al.  Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. , 2003, Archives of neurology.

[68]  T. Perls,et al.  Distinguishing Between Neurodegenerative Disease and Disease-Free Aging: Correlating Neuropsychological Evaluations and Neuropathological Studies in Centenarians , 2002, Psychosomatic medicine.

[69]  W. Markesbery,et al.  Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: Findings from the Nun Study , 2002, Annals of neurology.

[70]  W. Markesbery,et al.  Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer’s disease , 2002, Neurobiology of Aging.

[71]  Kyoko Suzuki,et al.  Regional quantitative analysis of NFT in brains of non‐demented elderly persons: Comparisons with findings in brains of late‐onset Alzheimer’s disease and limbic NFT dementia , 2002, Neuropathology : official journal of the Japanese Society of Neuropathology.

[72]  J. Schneider,et al.  Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease , 2002, Annals of neurology.

[73]  S. Corkin.  What's new with the amnesic patient H.M.? , 2002, Nature Reviews Neuroscience.

[74]  J. Kril,et al.  Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation , 2002, Acta Neuropathologica.

[75]  J. Bohl,et al.  Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer's disease , 2002, Acta Neuropathologica.

[76]  W. Jagust,et al.  The effects of age on rate of progression of Alzheimer disease and dementia with associated cerebrovascular disease. , 2001, Archives of neurology.

[77]  E. Otomo,et al.  Senile Dementia of the Neurofibrillary Tangle Type: A Comparison with Alzheimer’s Disease , 2001, Dementia and Geriatric Cognitive Disorders.

[78]  H. Braak,et al.  The evolution of Alzheimer's disease‐related cytoskeletal pathology in the human raphe nuclei , 2000, Neuropathology and applied neurobiology.

[79]  J. Schneider,et al.  Novel Method to Quantify Neuropil Threads in Brains from Elders With or Without Cognitive Impairment , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[80]  I. Skoog.  Detection of preclinical Alzheimer's disease. , 2000, The New England journal of medicine.

[81]  J. Ashford,et al.  “Preclinical” AD revisited , 2000, Neurology.

[82]  H. Braak,et al.  Sequence of Aβ‐Protein Deposition in the Human Medial Temporal Lobe , 2000 .

[83]  Patrick R. Hof,et al.  Tau protein isoforms, phosphorylation and role in neurodegenerative disorders 1 1 These authors contributed equally to this work. , 2000, Brain Research Reviews.

[84]  P. Hof,et al.  Clinical validity of Braak neuropathological staging in the oldest-old , 2000, Acta Neuropathologica.

[85]  R. Lipton,et al.  The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians. , 2000, Archives of neurology.

[86]  C. Brayne,et al.  Neuropathological Findings in the Very Old: Results from the First 101 Brains of a Population‐based Longitudinal Study of Dementing Disorders , 2000, Annals of the New York Academy of Sciences.

[87]  H. Braak,et al.  Sequence of Abeta-protein deposition in the human medial temporal lobe. , 2000, Journal of neuropathology and experimental neurology.

[88]  J. Growdon,et al.  Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer disease. , 1999, Journal of neuropathology and experimental neurology.

[89]  K. Davis,et al.  Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. , 1999, Archives of neurology.

[90]  F. Schmitt,et al.  Alzheimer neuropathologic alterations in aged cognitively normal subjects. , 1999, Journal of neuropathology and experimental neurology.

[91]  J. Morris,et al.  Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease , 1999, Annals of neurology.

[92]  P. Coleman,et al.  Neurons may live for decades with neurofibrillary tangles. , 1999, Journal of neuropathology and experimental neurology.

[93]  D. Mash,et al.  Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. , 1998, Journal of neuropathology and experimental neurology.

[94]  Brent A. Vogt,et al.  Multivariate Analysis of Laminar Patterns of Neurodegeneration in Posterior Cingulate Cortex in Alzheimer's Disease , 1998, Experimental Neurology.

[95]  L. Thal,et al.  Cognitive decline is faster in Lewy body variant than in Alzheimer's disease , 1998, Neurology.

[96]  K. Kosaka,et al.  Recent advances in dementia research in Japan: Non‐Alzheimer‐type degenerative dementias , 1998, Psychiatry and clinical neurosciences.

[97]  J. Price,et al.  Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. , 1998, Archives of neurology.

[98]  V. Hachinski,et al.  Fallacies in the pathological confirmation of the diagnosis of Alzheimer’s disease , 1998, Journal of neurology, neurosurgery, and psychiatry.

[99]  J. Trojanowski,et al.  Editorial on Consensus Recommendations for the Postmortem Diagnosis of Alzheimer Disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer Disease , 1997, Journal of neuropathology and experimental neurology.

[100]  James A. Mortimer,et al.  Brain Infarction and the Clinical Expression of Alzheimer Disease-Reply , 1997 .

[101]  G C Roman,et al.  Brain infarction and the clinical expression of Alzheimer disease. , 1997, JAMA.

[102]  S. Mirra.  The CERAD Neuropathology Protocol and Consensus Recommendations for the Postmortem Diagnosis of Alzheimer’s Disease: A Commentary , 1997, Neurobiology of Aging.

[103]  John Q. Trojanowski,et al.  Consensus Recommendations for the Postmortem Diagnosis of Alzheimer’s Disease , 1997, Neurobiology of Aging.

[104]  C. Duyckaerts,et al.  Modeling the Relation Between Neurofibrillary Tangles and Intellectual Status , 1997, Neurobiology of Aging.

[105]  J. Wegiel,et al.  Relationships between Regional Neuronal Loss and Neurofibrillary Changes in the Hippocampal Formation and Duration and Severity of Alzheimer Disease , 1997, Journal of neuropathology and experimental neurology.

[106]  W. Markesbery,et al.  Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. , 1997, JAMA.

[107]  Richard Hollister,et al.  Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease , 1997, Annals of neurology.

[108]  H. Braak,et al.  Staging of Alzheimer-related cortical destruction. , 1997, International psychogeriatrics.

[109]  Brian J Cummings,et al.  β-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease , 1996, Neurobiology of Aging.

[110]  D. Dickson,et al.  Neurodegenerative disorders with extensive tau pathology: A comparative study and review , 1996, Annals of neurology.

[111]  J. Price,et al.  Cerebral amyloid deposition and diffuse plaques in ``normal'' aging , 1996, Neurology.

[112]  D. Graham,et al.  Altered β-APP Metabolism After Head Injury and its Relationship to the Aetiology of Alzheimer’s Disease , 1996 .

[113]  Brian J Cummings,et al.  Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease. , 1996, Neurobiology of aging.

[114]  D. Graham,et al.  Altered beta-APP metabolism after head injury and its relationship to the aetiology of Alzheimer's disease. , 1996, Acta neurochirurgica. Supplement.

[115]  P. Hof,et al.  Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients. , 1995, Archives of neurology.

[116]  Nigel J. Cairns,et al.  Neurons, intracellular and extracellular neurofibrillary tangles in subdivisions of the hippocampal cortex in normal ageing and Alzheimer's disease , 1995, Neuroscience Letters.

[117]  H. Braak,et al.  Staging of alzheimer's disease-related neurofibrillary changes , 1995, Neurobiology of Aging.

[118]  A. Smith,et al.  Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria. , 1995, Dementia.

[119]  Claudia H. Kawas,et al.  The epidemiology of dementia and Alzheimer disease. , 1994 .

[120]  E. Masliah,et al.  Plaque‐Only Alzheimer Disease is Usually the Lewy Body Variant, and Vice Versa , 1993, Journal of neuropathology and experimental neurology.

[121]  W. Benzing,et al.  Immunocytochemical distribution of peptidergic and cholinergic fibers in the human amygdala: their depletion in Alzheimer's disease and morphologic alteration in non-demented elderly with numerous senile plaques , 1993, Brain Research.

[122]  M. Sliwinski,et al.  Pathological markers associated with normal aging and dementia in the elderly , 1993, Annals of neurology.

[123]  W. Markesbery,et al.  Morphometric image analysis of neuropil threads in alzheimer's disease , 1993, Neurobiology of Aging.

[124]  J. Miller,et al.  Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older. , 1993, Archives of neurology.

[125]  Bradley T. Hyman,et al.  Distribution of Alzheimer‐type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease , 1992, Neurology.

[126]  Bradley T. Hyman,et al.  Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease , 1992, Neurology.

[127]  J. Ulrich.  Abundant neurofibrillary tangles without senile plaques in a subset of patients with senile dementia , 1992 .

[128]  A. Paetau,et al.  Histamine neurons in human hypothalamus: Anatomy in normal and alzheimer diseased brains , 1991, Neuroscience.

[129]  T. Ogihara,et al.  The 717Val----Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. , 1991, Biochemical and biophysical research communications.

[130]  J. Price,et al.  The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease , 1991, Neurobiology of Aging.

[131]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[132]  H. Wiśniewski,et al.  Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques. , 1991, Acta Neuropathologica.

[133]  D. Allsop,et al.  The occult aftermath of boxing. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[134]  W. Benzing,et al.  Substance P and somatostatin coexist within neuritic plaques: Implications for the pathogenesis of Alzheimer's disease , 1989, Neuroscience.

[135]  H. Braak,et al.  Alzheimer's disease: Mismatch between amyloid plaques and neuritic plaques , 1989, Neuroscience Letters.

[136]  I. Izquierdo,et al.  Mechanism of action of scopolamine as an amnestic. , 1989, Trends in pharmacological sciences.

[137]  D. Price,et al.  The neuropathology of aminergic nuclei in Alzheimer's disease , 1988, Progress in clinical and biological research.

[138]  J. Morris,et al.  The association of ventral tegmental area histopathology with adult dementia. , 1988, Archives of neurology.

[139]  C. Filley.  Diagnosis of Alzheimer's disease. , 1988, Colorado medicine.

[140]  T. Erkinjuntti,et al.  Suspected dementia: evaluation of 323 consecutive referrals , 1987, Acta neurologica Scandinavica.

[141]  D. German,et al.  Alzheimer's disease: Neurofibrillary tangles in nuclei that project to the cerebral cortex , 1987, Neuroscience.

[142]  R. Katzman.,et al.  Senile Dementia of the Alzheimer Type Without Neocortical Neurofibrillary Tangles , 1987, Journal of neuropathology and experimental neurology.

[143]  D. Selkoe,et al.  Neurofibrillary degeneration of cholinergic and noncholinergic neurons of the basal forebrain in Alzheimer's disease , 1986, Annals of neurology.

[144]  H. Braak,et al.  Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: A third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques , 1986, Neuroscience Letters.

[145]  D. German,et al.  Neuronal pathology in the nucleus basalis and associated cell groups in senile dementia of the Alzheimer's type , 1985, Neurology.

[146]  C. Saper,et al.  A cytoarchitectonic and histochemical study of nucleus basalis and associated cell groups in the normal human brain , 1984, Neuroscience.

[147]  J. Brust.  Dementia and cerebrovascular disease. , 1983, Advances in neurology.

[148]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[149]  H. Wiśniewski,et al.  Pathogenesis of neuritic (senile) and amyloid plaque formation. , 1982, Experimental brain research.

[150]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[151]  R. Elston,et al.  Specificity of the clinical diagnosis of dementia , 1975, Journal of the Neurological Sciences.

[152]  S. Otsuki,et al.  Frequency of Alzheimer's Neurofibrillary Tangles in the Basal Ganglia and Brain‐stem in Alzheimer's Disease, Senile Dementia and the Aged , 1975, Folia psychiatrica et neurologica japonica.

[153]  H. Wiśniewski,et al.  NEURITIC (SENILE) PLAQUES AND FILAMENTOUS CHANGES IN AGED RHESUS MONKEYS , 1973, Journal of neuropathology and experimental neurology.

[154]  Alistair Burns,et al.  Observations on the brains of demented old people. B.E. Tomlinson, G. Blessed and M. Roth, Journal of the Neurological Sciences (1970) 11, 205–242; (1968) 7, 331–356 , 1997 .

[155]  W. Scoville,et al.  LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS , 1957, Journal of neurology, neurosurgery, and psychiatry.