There is evidence suggesting that although amnestic MCI patients may not meet neuropathologic criteria for Alzheimer's disease, patients may be in a transitional stage of evolving Alzheimer's disease; patients in this hypothesized transitional stage demonstrated diffuse amyloid in the neocortex and frequent neurofibrillary tangles in the medial temporal lobe. Alternatively, many individuals develop neurofibrillary tangles without amyloid, a pattern termed primary age-related tauopathy.

There is emerging evidence that magnetic resonance imaging can observe deterioration, including progressive loss of gray matter in the brain, from mild cognitive impairment to full-blown Alzheimer disease. A technique known as PiB PET imaging is used to clearly show the sites and shapes of beta amyloid deposits in living subjects using a tracer that binds selectively to such deposits. Such tools may help greatly in assisting clinical research for therapies.

The diagnosis of MCI requires considerable clinical judgement, and as such a comprehensive clinical assessment including clinical observation, neuroimaging, blood tests and neuropsychological testing are best in order to rule out an alternate diagnosis.

MCI is diagnosed when there is:

1. Evidence of memory impairment

2. Preservation of general cognitive and functional abilities

3. Absence of diagnosed dementia

There are some brief tests (5–15 minutes) that have reasonable reliability to screen for dementia.

While many tests have been studied, presently the mini mental state examination (MMSE) is the best studied and most commonly used. The MMSE is a useful tool for helping to diagnose dementia if the results are interpreted along with an assessment of a person's personality, their ability to perform activities of daily living, and their behaviour. Other cognitive tests include the abbreviated mental test score (AMTS), the, "Modified Mini-Mental State Examination" (3MS), the "Cognitive Abilities Screening Instrument" (CASI), the Trail-making test, and the clock drawing test. The MOCA (Montreal Cognitive Assessment) is a very reliable screening test and is available online for free in 35 different languages. The MOCA has also been shown somewhat better at detecting mild cognitive impairment than the MMSE.

Another approach to screening for dementia is to ask an informant (relative or other supporter) to fill out a questionnaire about the person's everyday cognitive functioning. Informant questionnaires provide complementary information to brief cognitive tests. Probably the best known questionnaire of this sort is the "Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)". There is not sufficient evidence to determine how accurate the IQCODE is for diagnosing or predicting dementia. The Alzheimer's Disease Caregiver Questionnaire is another tool. It is about 90% accurate for Alzheimer's and can be completed online or in the office by a caregiver. On the other hand, the "General Practitioner Assessment Of Cognition" combines both, a patient assessment and an informant interview. It was specifically designed for the use in the primary care setting.

Clinical neuropsychologists provide diagnostic consultation following administration of a full battery of cognitive testing, often lasting several hours, to determine functional patterns of decline associated with varying types of dementia. Tests of memory, executive function, processing speed, attention, and language skills are relevant, as well as tests of emotional and psychological adjustment. These tests assist with ruling out other etiologies and determining relative cognitive decline over time or from estimates of prior cognitive abilities.

Routine blood tests are also usually performed to rule out treatable causes. These tests include vitamin B, folic acid, thyroid-stimulating hormone (TSH), C-reactive protein, full blood count, electrolytes, calcium, renal function, and liver enzymes. Abnormalities may suggest vitamin deficiency, infection, or other problems that commonly cause confusion or disorientation in the elderly.

Of the many medical imaging techniques available, single photon emission computed tomography (SPECT) appears to be superior in differentiating Alzheimer's disease from other types of dementia, and this has been shown to give a greater level of accuracy compared with mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.

PiB PET remains investigational, but a similar PET scanning radiopharmaceutical called florbetapir, containing the longer-lasting radionuclide fluorine-18, has recently been tested as a diagnostic tool in Alzheimer's disease, and given FDA approval for this use.

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.

In 2011 An FDA panel voted unanimously to recommend approval of florbetapir, which is currently used in an investigational study. The imaging agent can help to detect Alzheimer's brain plaques, but will require additional clinical research before it can be made available commercially.

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 AD 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 AD 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 AD 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.

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 AD—causes which may, in rare cases, be reversible. It is common to perform thyroid function tests, assess B12, rule out syphilis, rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels of heavy metals (e.g. lead, mercury) and anaemia. (It is also necessary to rule out delirium).

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

Due to low accuracy, the C-PIB-PET scan is not recommended to be used as an early diagnostic tool or for predicting the development of Alzheimer's disease when people show signs of mild cognitive impairment (MCI). The use of ¹⁸F-FDG PET scans, as a single test, to identify people who may develop Alzheimer's disease is also not supported by evidence.

There have been assertions of a possible link between TGA and the use of statins (a class of drug used in treating cholesterol).

En bloc memory loss which is total, permanent, and irrecoverable can occur as an alcoholic "black out," usually lasting longer than an hour and up to 2–5 days.

Marijuana intoxication, Halogenated hydroxyquinolines such as Clioquinol, PDE inhibitors such as sildenafil, Digitalis and scopolamine intoxication, and general anaesthesia have been reported with TGA.

The body's inflammatory response to surgery likely plays an important role, at least in elderly patients. Various research initiatives during recent years have evaluated whether actions taken before, during and after surgery can lessen the possible deleterious effects of inflammation. For example, anti-inflammatory agents can be given before surgery. During surgery, inflammation can be modulated by temperature control, use of regional rather than general anesthesia or the use of beta blockers. After surgery, optimal pain management and infection control is important. Several studies have shown variable-significance positive effects when a multidisciplinary, multifactorial approach to elderly patient is followed during pre, peri and post-operative care.

Animal studies indicate that volatile anaesthestics may augment the pathological processes of Alzheimer's Disease by affecting amyloid-beta processing. However, in young healthy mice, the volatile anesthetic isoflurane can also produce long-lasting memory impairment. This adverse effect is preventable by pre-administering the GABA(A)α5 inverse agonist L-655,708.

The prognosis of "pure" TGA is very good. It does not affect mortality or morbidity and unlike earlier understanding of the condition, TGA is not a risk factor for stroke or ischemic disease. Rates of recurrence are variously reported, with one systematic calculation suggesting the rate is under 6% per year. TGA "is universally felt to be a benign condition which requires no further treatment other than reassurance to the patient and his or her family."

"The most important part of management after diagnosis is looking after the psychological needs of the patient and his or her relatives. Seeing a once competent and healthy partner, sibling or parent become incapable of remembering what was said only a minute ago is very distressing, and hence it is often the relatives who will require reassurance."

TGA may have multiple etiologies and prognoses. Atypical presentations may masquerade as epilepsy and be more properly considered TEA. In addition to such probable TEA cases, some people experiencing amnestic events diverging from the diagnostic criteria articulated above may have a less benign prognosis than those with "pure" TGA.

Recently, moreover, both imaging and neurocognitive testing studies question whether TGA is as benign as has been thought. MRI scans of the brain in one study showed that among people who had experienced TGA, all had cavities in the hippocampus, and these cavities were far more numerous, larger, and more suggestive of pathological damage than in either healthy controls or a large control group of people with tumor or stroke. Verbal and cognitive impairments have been observed days after TGA attacks, of such severity that the researchers estimated the effects would be unlikely to resolve within a short time frame. A large neurocognitive study of patients more than a year after their attack has shown persistent effects consistent with amnestic mild cognitive impairment (MCI-a) in a third of the people who had experienced TGA. In another study, "selective cognitive dysfunctions after the clinical recovery" were observed, suggesting a prefrontal impairment. These dysfunctions may not be in memory "per se" but in retrieval, in which speed of access is part of the problem among people who have had TGA and experience ongoing memory problems.

POCD is common after cardiac surgery, and recent studies have now verified that POCD also exists after major non-cardiac surgery, although at a lower incidence. The risk of POCD increases with age, and the type of surgery is also important because there is a very low incidence associated with minor surgery. POCD is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 years or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery. Research interest has increased since early 2000, especially as more elderly patients are able to undergo successful minor and major surgeries.

POCD has been studied through various institutions since the inception of the IPOCDS-I study centred in Eindhoven, Netherlands and Copenhagen, Denmark. This study found no causal relationship between cerebral hypoxia and low blood pressure and POCD. Age, duration of anaesthesia, introperative complications, and postoperative infections were found to be associated with POCD.

- POCD is just as likely to occur after operations under regional anesthesia as under general anesthesia.

- More likely after major operations than minor operations.

- More likely after heart operations than other types of surgery.

- More likely in aged than in younger patients.

- More likely in older patients with high alcohol intake/abuse.

- People with higher preoperative ASA physical status scores are more likely to develop POCD.

- People with lower educational level are more likely to develop POCD than those with a higher educational level.

- People with prior history of a stroke, even though there is complete functional recovery, are more likely to develop POCD.

- More likely in the elderly with pre-existing declining mental functions, termed mild cognitive impairment (MCI). MCI is a transitional zone between normal mental function and evident Alzheimer's disease or other forms of dementia. It is insidious, and seldom recognized, except in retrospect after affected persons are evidently demented.

- Delirium and severe worsening of mental function is very likely in those with clinically evident Alzheimer's disease or other forms of dementia, as well as those with a history of delirium after previous operations.