Details of the studies on early AD conducted at our center have been published. The population for these studies are the residents of the Jewish Home and Hospital (JHH), a long-term care facility affiliated with the Mount Sinai School of Medicine in New York.
The two main campuses of the JHH have approximately 1,600 residents, with an average age of over 85. Cognitive screening is a routine part of clinical care in the JHH, and Mini-Mental State Examination (MMSE)
scores are available for nearly all residents. For the early AD study, all consenting residents with MMSE scores of 15 or greater are given a thorough diagnostic evaluation and are assigned a score on the Clinical
Dementia Rating (CDR; Morris et al., 1993). Those with CDR scores of 0 (no dementia), 0.5 (questionable dementia), or 1.0 (mild dementia) are administered a battery of neuropsychological tests.
The JHH routinely requests autopsy permission when a resident dies and, over the period of the early AD project, more than 50 autopsies have been obtained from residents who died with CDR scores of 0 to 1.0, and evidenced either no significant neuropathology or had neuropathologic lesions associated with AD only. As might be expected with cases from a long-term care facility, many more autopsies have been obtained from residents who died with more severe dementia or with comorbid neuropathologic lesions.
Neuropathologic studies of cases dying with no dementia, questionable dementia, or mild dementia have shown that senile plaques are more abundant in most areas of the neocortex in patients with CDR 0.5 than in persons dying without any evidence of dementia (CDR 0) (Haroutunian et al., 1998). Examination of specific amyloid fragments has shown that the Afi peptides, especially the A^ 42 peptide, are markedly elevated even in the CDR 0.5 cases, compared with the CDR 0 cases (Naslund et al., 2000). By contrast, neurofibrillary tangles were evident in the entorhinal cortex and hippocampus of virtually all brains from
persons over age 80, even those from nondemented individuals; extensive neurofibrillary tangles in the neocortex were evident only in patients with CDR 2.0 (moderate dementia) or greater (Haroutunian et al., 1999). These data support the view that overproduction and accumulation of amyloid protein, particularly the ^ 42 fragment, is a very early manifestation of AD. Neurofibrillary tangles in entorhinal cortex and hippocampus are age-related phenomena that are further influenced by AD as dementia progresses
from severe to terminal, while the development of tangles in the neocortex is associated with progression to moderate and severe dementia.
Other biologic manifestations of AD have also been examined in this series. Cholinergic markers, including choline acetyltransferase (ChAT) and acetylcholinesterase, were not diminished in early AD cases, but were reduced substantially in those patients dying with moderate-to-severe dementia (Davis et al., 1999a).
The two main campuses of the JHH have approximately 1,600 residents, with an average age of over 85. Cognitive screening is a routine part of clinical care in the JHH, and Mini-Mental State Examination (MMSE)
scores are available for nearly all residents. For the early AD study, all consenting residents with MMSE scores of 15 or greater are given a thorough diagnostic evaluation and are assigned a score on the Clinical
Dementia Rating (CDR; Morris et al., 1993). Those with CDR scores of 0 (no dementia), 0.5 (questionable dementia), or 1.0 (mild dementia) are administered a battery of neuropsychological tests.
The JHH routinely requests autopsy permission when a resident dies and, over the period of the early AD project, more than 50 autopsies have been obtained from residents who died with CDR scores of 0 to 1.0, and evidenced either no significant neuropathology or had neuropathologic lesions associated with AD only. As might be expected with cases from a long-term care facility, many more autopsies have been obtained from residents who died with more severe dementia or with comorbid neuropathologic lesions.
Neuropathologic studies of cases dying with no dementia, questionable dementia, or mild dementia have shown that senile plaques are more abundant in most areas of the neocortex in patients with CDR 0.5 than in persons dying without any evidence of dementia (CDR 0) (Haroutunian et al., 1998). Examination of specific amyloid fragments has shown that the Afi peptides, especially the A^ 42 peptide, are markedly elevated even in the CDR 0.5 cases, compared with the CDR 0 cases (Naslund et al., 2000). By contrast, neurofibrillary tangles were evident in the entorhinal cortex and hippocampus of virtually all brains from
persons over age 80, even those from nondemented individuals; extensive neurofibrillary tangles in the neocortex were evident only in patients with CDR 2.0 (moderate dementia) or greater (Haroutunian et al., 1999). These data support the view that overproduction and accumulation of amyloid protein, particularly the ^ 42 fragment, is a very early manifestation of AD. Neurofibrillary tangles in entorhinal cortex and hippocampus are age-related phenomena that are further influenced by AD as dementia progresses
from severe to terminal, while the development of tangles in the neocortex is associated with progression to moderate and severe dementia.
Other biologic manifestations of AD have also been examined in this series. Cholinergic markers, including choline acetyltransferase (ChAT) and acetylcholinesterase, were not diminished in early AD cases, but were reduced substantially in those patients dying with moderate-to-severe dementia (Davis et al., 1999a).
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