Alzheimer's treatment

Alzheimer’s disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions. Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computed tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia. Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer’s disease.

Assessment of intellectual functioning including memory testing can further characterise the state of the disease. Medical organisations have created diagnostic criteria to ease and standardise the diagnostic process for practicing physicians. The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.
Criteria

The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (Alzheimer diseaseRDA, now known as the Alzheimer’s Association) established the most commonly used NINCDS-Alzheimer diseaseRDA Alzheimer’s Criteria for diagnosis in 1984, extensively updated in 2007. These criteria require that the presence of cognitive impairment, and a suspected dementia syndrome, be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable Alzheimer disease. A histopathologic confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. Good statistical reliability and validity have been shown between the diagnostic criteria and definitive histopathological confirmation. Eight cognitive domains are most commonly impaired in Alzheimer disease-memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities. These domains are equivalent to the NINCDS-Alzheimer diseaseRDA Alzheimer’s Criteria as listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) published by the American Psychiatric Association.
Techniques
Neuropsychological screening tests can help in the diagnosis of Alzheimer disease. In them patients have to copy drawings similar to the one shown in the picture, remember words, read, and subtract serial numbers.

Neuropsychological tests such as the mini-mental state examination (MMSE), are widely used to evaluate the cognitive impairments needed for diagnosis. More comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease. Neurological examination in early Alzheimer disease will usually provide normal results, except for obvious cognitive impairment, which may not differ from that resulting from other diseases processes, including other causes of dementia.

Further neurological examinations are crucial in the differential diagnosis of Alzheimer disease and other diseases. Interviews with family members are also utilised in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease, over time, of the person’s mental function. A caregiver’s viewpoint is particularly important, since a person with Alzheimer disease is commonly unaware of his own deficits. Many times, families also have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician.

Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins, both total tau protein and phosphorylated tau181P protein concentrations. Searching for these proteins using a spinal tap can predict the onset of Alzheimer’s with a sensitivity of between 94% and 100%. When used in conjunction with existing neuroimaging techniques, doctors can identify patients with significant memory loss who are already developing the disease. Spinal fluid tests are commercially available, unlike the latest neuroimaging technology. Alzheimer’s was diagnosed in one-third of the people who did not have any symptoms in a 2010 study, meaning that disease progression occurs well before symptoms occur.

Supplemental testing provides extra information on some features of the disease or is used to rule out other diagnoses. Blood tests can identify other causes for dementia than Alzheimer disease-causes which may, in rare cases, be reversible. It is common to perform thyroid function tests, assess B12, rule out syphillis, rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels of heavy metals (e.g. lead, mercury) and anemia. (See differential diagnosis for Dementia). (It is also necessary to rule out delirium).

Psychological tests for depression are employed, since depression can either be concurrent with Alzheimer disease (see Depression of Alzheimer disease), an early sign of cognitive impairment, or even the cause.
Imaging

When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging are used to confirm a diagnosis of Alzheimer’s in conjunction with evaluations involving mental status examination. In a person already having dementia, SPECT appears to be superior in differentiating Alzheimer’s disease from other possible causes, compared with the usual attempts employing mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.

A new technique known as PiB PET has been developed for directly and clearly imaging beta-amyloid deposits in vivo using a tracer that binds selectively to the A-beta deposits. The PiB-PET compound uses carbon-11 PET scanning. Recent studies suggest that PiB-PET is 86% accurate in predicting which people with mild cognitive impairment will develop Alzheimer’s disease within two years, and 92% accurate in ruling out the likelihood of developing Alzheimer’s.

A similar PET scanning radiopharmaceutical compound called (E)-4-(2-(6-(2-(2-(2-(-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine, or 18F AV-45, or florbetapir-fluorine-18, or simply florbetapir, contains the longer-lasting radionuclide fluorine-18, has recently been created, and tested as a possible diagnostic tool in Alzheimer’s patients.Florbetapir, like PiB, binds to beta-amyloid, but due to its use of fluorine-18 has a half-life of 110 minutes, in contrast to PiB’s radioactive half life of 20 minutes. Wong et al. found that the longer life allowed the tracer to accumulate significantly more in the brains of the Alzheimer disease patients, particularly in the regions known to be associated with beta-amyloid deposits.

One review predicted that amyloid imaging is likely to be used in conjunction with other markers rather than as an alternative.

Volumetric MRI can detect changes in the size of brain regions. Measuring those regions that atrophy during the progress of Alzheimer’s disease is showing promise as a diagnostic indicator. It may prove less expensive than other imaging methods currently under study.
Non-Imaging biomarkers

Recent studies have shown that patients with Alzheimer disease had decreased glutamate (Glu) as well as decreased Glu/creatine (Cr), Glu/myo-inositol (mI), Glu/N-acetylaspartate (NAA), and NAA/Cr ratios compared to normal patients. Both decreased NAA/Cr and decreased hippocampal glutamate may be an early indicator of Alzheimer disease.

Early research in mouse models may have identified markers for Alzheimer disease. The applicability of these markers to human patients is unknown.

A small human study in 2011 found that monitoring blood dehydroepiandrosterone (DHEA) variations in response to an oxidative stress could be a useful proxy test: the subjects with MCI did not have a DHEA variation, while the healthy controls did.