If one of the foregoing restricted deficits remains uncomplicated over a long period, one is justified in suspecting a cause other than Alzheimer disease, such as one of the lobar atrophies such as frontotemporal dementia (see further on), Binswanger disease, hydrocephalus, or embolic infarctions of the temporal or parietal lobes. Each of the restricted clinical disorders described above is only relatively pure. Careful testing of mental function—and this is of diagnostic importance—frequently discloses subtle abnormalities in several cognitive spheres. Initially, most patients have a disproportionate disorder of the temporoparietal cortices, reflected by an earlier impairment on the performance parts of the Wechsler Adult Intelligence Scale. Within a year or two, the more generalized aspects of mental deterioration become apparent, and the aphasic–agnosic–apraxic aspects of the syndrome become increasingly prominent. Although it is true that most patients with Alzheimer disease walk normally until relatively late in their illness, infrequently a short-stepped gait and imbalance draw attention to the disease and worsen slowly for several years before cognitive manifestations become evident. The general decrepitude in appearance that accompanies the middle and late stages of the disease in many patients is commented on in Chap. 20.
For research purposes and to establish certain inclusive and exclusive criteria for the diagnosis of Alzheimer disease, a working group of the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Diseases Association (ADRDA) in the past proposed the following criteria: (1) dementia defined by clinical examination, the Mini-Mental Scale, the Blessed Dementia Scale, or similar mental status examination—currently the Alzheimer Disease Assessment Scale (ADAS, which has 2 components, 1 for cognition, ADAS-cog and the other for activities of daily living, ADAS-ADL) is often used; (2) patient older than age 40 years; (3) deficits in 2 or more areas of cognition and progressive worsening of memory and other cognitive functions, such as language, perception, and motor skills (praxis); (4) absence of disturbed consciousness; and (5) exclusion of other brain diseases (McKhann et al, 1984; Tierney et al, 1988). These criteria have essentially been reaffirmed by more recent consensus panels (see McKhann et al, 2011). Using these measures, the correct diagnosis is achieved in more than 85 percent of patients, but this is not surprising given that Alzheimer disease is overwhelmingly the most common cause of adult dementia. Most cases are identifiable without resorting to restrictive lists such as these, especially if the patient is observed serially over a period of months or years. There is strong interest in the addition of biomarkers such as positron emission tomography (PET) ligand for amyloid and tau/amyloid ratio in CSF to the diagnostic criteria for the disease but the diagnosis remains predominantly a clinical one, aided by imaging and other tests.
In the advanced stages of the disease, the brain presents a diffusely atrophied appearance and its weight is usually reduced by 20 percent or more. Cerebral convolutions are narrowed and sulci are widened. The third and lateral ventricles are symmetrically enlarged to varying degrees. Usually, the atrophic process involves the frontal, temporal, and parietal lobes, but cases vary considerably. The extreme atrophy of the hippocampus, the most prominent finding visible on MRI (mainly coronal images), is diagnostic in the proper clinical circumstances.