References

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 3rd ed-Revised. Washington, DC 1987. 2. Fleming KC, Adams AC, Petersen RC. Dementia diagnosis and evaluation. Mayo. Clin. Proc. 1995 70 1093-1107. 3. Joachim CL, Morris JH, Selkoe DJ. Clinically diagnosed Alzheimer's disease autopsy neuropathological results in 150 cases. Ann. Neurol. 1988 24 50-56. 4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's...

Ap Deposition Appears To Be a Necessary but Not Sufficient Factor for the Genesis of AD

To summarize at this juncture, four genes that are unequivocally associated with the development of AD have been identified to date, and linkage analyses of other families make it clear that additional genes can be responsible (Table 1). Three of the known genes, APP on chromosome 21, PS-1 on chromosome 14, and PS-2 on chromosome 1, can be said to be causative of AD in the respective families in which mutations in these genes occur. In each of these three cases, there is now compelling evidence...

Clinical Versus Pathological Dimensions of AD

Rigorous study of a progressive neurological disease such as AD requires that we appreciate the distinction between its clinical and pathological dimensions. Clinically, AD most commonly manifests as an insidiously progressive decline in cognitive and functional status, with salient disruption of memory and other intellectual functions (see Chapter 2 for clinical definitions of AD). There are several different, but largely overlapping sets of criteria that specify the pattern of symptoms and...

Medial Temporal Lobe Atrophy

Although almost every study in which imaging measures of global or hemispheric atrophy have been employed has identified a statistically significant difference between the mean value found in AD patients and that found in control subjects, invariably substantial overlap exists between individual members of these two populations which in turn limits the clinical utility of this approach for diagnosis in individual patients (20). It is highly likely that this overlap between controls and AD...

The Acute Phase Response and Alzheimer Disease

The acute phase response (APR) is an orchestrated physiological response of the body to tissue injury, infection, or inflammation. A prominent feature of the APR is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines including interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-a) are important mediators of the APR. Different signaling pathways are activated by different cytokine-recep-tor interactions. Eventually,...

Lewy Body Variant

Lewy bodies (LB) are intracytoplasmic inclusions (74). They appear as a dense eosinophilic core surrounded by a less densely stained peripheral halo. The LB is a pathological hallmark of brains of patients suffering from Parkinson's disease (PD), within which LB are found most prominently in the substantia nigra (SN) and other subcortical nuclei. Sparsely distributed cortical LB are also found in most PD cases. The cortical LB are observed mostly in nonpyramidal neurons of layers V and VI (74)....

Dementia Associated with Sensorimotor Signs

A third major pattern in dementia is one in which cognitive decline is accompanied by sensory and motor signs. Most often, the salient mental state changes of these dementias also involve complex attention, behavior, and personality. Changes in executive functions are not universal, but depend on where the brunt of the neuropathology is located. Table 7 lists a number of disease processes that tend to have this dementia profile. The disease entity in this category with the highest prevalence is...

Assessing the Value of Candidate Tests The Problem of No Gold Standard

As noted above, one of the greatest challenges facing the assessment of candidate early markers for AD, especially those in the presymptomatic phase of the illness, is the lack of an appropriate in vivo gold standard upon which to make a judgment. Consider, for example, two biological markers that are tested on a group of elderly individuals who currently are not clinically demented. If one of the markers is positive in a portion of these elders and the other is negative in all cases, how do we...

Mild Cognitive Impairment in the Elderly At Risk or Preclinical Dementia

Despite living independently in the community, many elders show some degree of abnormal cognitive decline on standardized testing. When community dwelling elders with mild cognitive impairments are studied longitudinally, some go on to develop dementia 56-59 while some do not 60-61 . The presence of mild cognitive problems, by themselves, in community dwelling elders, is not necessarily predictive of a preclinical stage of Alzheimer's disease but can also be associated with the variability seen...

Diagnostic Classification

Several studies have attempted to calculate the diagnostic accuracy of PET or SPECT in differentiating AD from normal controls. The studies vary widely in the numbers of subjects, the severity of dementia, and the image analysis methodology. Most of the studies are plagued by lack of a gold standard, having limited numbers of autopsy-confirmed patients. A few studies have reported low sensitivity of functional image abnormalities in mild AD. Powers and colleagues 43 evaluated the...

Pathology of Normal Aging and Mild Dementia

A large number of investigations have indicated that SP and NFT can also occur in the brains of cognitively normal elderly 12,22,44,45 . SP and, in particular, A immunoreactive SP are commonly found in the cerebral cortex of many normal aged brains. In some of these brains, the density of A deposits has been found to be similar to that present in AD. NFT are also present in the normal aged brain. However, they are found less frequently, in much lower density and with very restricted...

Dementias With a Prominent Dysexecutive Syndrome

A second major dementia pattern involves patients who exhibit salient changes in personality and behavior, accompanied by compromised attention, motivation, judgment, insight, and other executive functions. This clinical entity has been given several names including frontotemporal dementia FTD , dementia of the frontal lobe type, and comportmental dementia 30,50,86-88 . In addition, there are overlapping features with the so-called subcortical dementias 89,90 . This overlap is likely due to the...

Sensorimotor Examination

The sensorimotor neurological examination does not contribute to making a diagnosis of dementia per se. However, the pattern of neurological abnormalities often point to likely underlying diseases that may be contributing to the dementing process. For example, a clinician should look for evidence of upper motor neuron signs e.g., hemiparesis, asymmetric deep tendon reflexes, extensor plantar responses that would suggest the possibility of stroke or structural lesion. Extrapyramidal signs would...