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Objectives: To identify patients with pure hippocampal sclerosis (HS) as a cause of dementia, to determine whether they have had histories of hypotension or hypoxia, and to compare the clinical features of patients with pure HS with a control group of AD patients without HS., Methods: In a retrospective study, the authors reviewed all 1771 cases received in their dementia brain bank from 1978 through 1996 to identify those patients with pure HS, defined as severe degeneration and gliosis of the CA1 sector and subiculum of the hippocampal formation in the absence of other significant dementing disease such as Alzheimer's changes. The control group included all patients received during the same period with severe AD without HS, infarcts, or other dementing disease., Results: Seven pure HS cases (0.4%) were identified. None had any episodes of syncope, hypotension, or hypoxia reported in association with dementia onset. Six had memory loss as the primary presenting symptom, and all became progressively demented. Forty-five AD patients without HS were identified for the control group. There were no clear clinical differences between the two groups with regard to sex, age at onset, risk factors for vascular disease, symptoms of cerebrovascular disease, treatment with tranquilizing medications, treatment for depression, or nursing home placement. There was a tendency for heart disease to be more prevalent and the duration of illness to be shorter in the patients with pure HS., Conclusions: Pure hippocampal sclerosis (HS) occurred in only 0.4% of our dementia patients. Clinically, the seven patients with pure HS were similar to our AD control group. Further research is needed to determine the causes of HS and why HS appears to mimic AD.

The NINCDS-ADRDA criteria for the clinical diagnosis of probable Alzheimer disease (AD) state that "gait disturbances at the onset or very early in the course of the illness make the diagnosis of Alzheimer disease uncertain or unlikely," yet there have been few studies documenting the validity of the statement. We therefore reviewed all cases of pure autopsy-proven AD in the Ramsey Brain Bank to determine how frequently an abnormal gait was noted at time of presentation. Any reported gait disturbance was considered an abnormal gait. Only cases for which medical records were available documenting the patient's presentation for dementia were included. Cases were excluded if any other pathology was present that may have contributed to the patient's dementia or to a gait disorder, if neuroleptic medication had been used, or if there was a preexisting gait disorder. Clinical dementia severity at time of presentation was graded as mild, moderate, or severe per DSM-IIIR criteria. Of the 95 cases that met study criteria, none of the 36 patients with mild dementia were reported to have had an abnormal gait. Sixteen percent of the patients with moderate and 32% with severe dementia had gait abnormalities reported. This study confirms the statement regarding gait in the NINCDS-ADRDA criteria.

The clinical recognition of Pick's disease depends on its differentiation from Alzheimer's disease (AD). To identify distinguishing clinical features, we reviewed the clinical records of 21 patients with pathologically confirmed Pick's disease and matched them by sex, age of onset, and duration of dementia with 42 patients having pathologically confirmed AD. In the absence of temporal or frontal lobar atrophy on CTs, all the Pick patients and none of the AD patients had three of five clinical features: presenile onset (before age 65), an initial personality change, hyperorality, disinhibition, and roaming behavior. In addition, the Pick patients had a tendency toward reiterative and other speech disturbances. These findings suggest that Pick patients are potentially distinguishable from AD patients on the basis of clinical manifestations.

We investigated potential risk factors for Alzheimer's disease (AD) in a clinicopathologic study of 407 patients with definite AD, 100 non-Alzheimer dementia patients, and 50 normal subjects. The AD patients had more first-degree relatives with dementia than the non-AD dementia group (odds ratio of 1.85, 95% confidence interval of 1.07-3.20) or the normal elderly (odds ratio of 3.60, 95% confidence interval of 1.50-8.64) but did not have significantly more head injuries, medical and psychiatric illnesses, or relatives with Down's syndrome. The AD patients with a family history of dementia had their dementia at a later age than those without an affected relative. These findings indicate a familial risk for AD that is greater than for other dementing illnesses and has age-related penetrance. This study does not support other putative risk factors for AD such as head trauma and familial Down's syndrome.

Despite the introduction of formal clinical criteria for Alzheimer disease (AD), the clinical diagnosis of AD remains one of exclusion of other dementias. To determine the accuracy of a clinical diagnosis of AD as made by practicing physicians, we reviewed the clinicopathologic records of a dementia brain bank and summarized the literature. Of 650 demented patients diagnosed during life as having AD, at autopsy 505 (78%) had AD with or without other neuropathologic conditions; only 390 (60%) of these had AD as the only neuropathologic condition. Of the remaining 145 (22%) patients with no neuropathologic evidence of AD, 39 had the nigrostriatal changes of Parkinson disease (PD), 25 had nonspecific degenerations, 15 had Pick disease, 14 had multiple infarcts, and 11 lacked any neuropathologic abnormality. Although the overall clinical accuracy for AD was lower than that summarized from the literature, clinical accuracy improved significantly between 1986 and 1990. In our broad sample of practitioners, accuracy of clinical diagnosis of AD may be improving, but continues to be hampered by difficulty in distinguishing the dementia of AD from certain dementing conditions and from AD mixed with other neuropathologic conditions.

From a series of 460 dementia patients referred to a regional brain bank, 14 (3%) patients had a pathologic diagnosis of primary degeneration of the brain involving multiple sites (frontoparietal cortex, striatum, medial thalamus, substantia nigra, and hypoglossal nucleus), with cell loss and astrocytosis. There were no neuronal inclusions and essentially no senile plaques. This entity, which we have termed "dementia lacking distinctive histology" (DLDH), presented with memory loss and personality changes, and led to death, usually within 2 to 7 years. Dysarthria and dysphagia were prominent in the later phases of the illness in most patients. The psychometric findings of some of the patients were consistent with a "frontal" lobe dementia. A few patients had prominent caudate atrophy on CT as well as neuropathologically. Eight of our patients had positive family histories for neurologic disease, mainly dementia. DLDH, in addition to Pick's disease, is a major member of the frontal-lobe dementia group. In patients under age 70 years, the frontal lobe dementias represent an important diagnostic consideration.

The ganglioside monoclonal antibody A2B5 has previously been used at the light microscopic level to label Alzheimer neurofibrillary tangles (NFTs). Light microscopic analysis, however, could not reveal whether the A2B5 antibody-labeled NFTs or membrane fragments associated with NFTs. Therefore, we used pre-embedding immunohistochemical electron microscopy to examine A2B5 labeling of NFT. We found that the A2B5 antibody does indeed label a NFT antigen associated with the paired helical filament (PHF) structure, while no significant labeling of membranes or membrane fragments was observed. However, no clear periodicity of the immunogold label on the PHF was found.

Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles both in isolated neurofibrillary tangle-bearing nerve cells and in partially purified preparations of tangle fibers. Antibody staining was preabsorbed by preincubation of antibody with neuronal ganglioside preparations. These results suggest that Alzheimer's neurofibrillary tangles have a ganglioside associated with them.