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.

At present, there is no definitive evidence to support that any particular measure is effective in preventing AD. Global studies of measures to prevent or delay the onset of AD have often produced inconsistent results.

Epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's likelihood of developing AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD.

Computed tomography (CT) scans of people with PD usually appear normal. MRI has become more accurate in diagnosis of the disease over time, specifically through iron-sensitive T2* and SWI sequences at a magnetic field strength of at least 3T, both of which can demonstrate absence of the characteristic 'swallow tail' imaging pattern in the dorsolateral substantia nigra. In a meta-analysis, absence of this pattern was 98% sensitive and 95% specific for the disease. Diffusion MRI has shown potential in distinguishing between PD and Parkinson plus syndromes, though its diagnostic value is still under investigation. CT and MRI are also used to rule out other diseases that can be secondary causes of parkinsonism, most commonly encephalitis and chronic ischemic insults, as well as less frequent entities such as basal ganglia tumors and hydrocephalus.

Dopamine-related activity in the basal ganglia can be directly measured with PET and SPECT scans. A finding of reduced dopamine-related activity in the basal ganglia can rule out drug-induced parkinsonism, but reduced basal ganglia dopamine-related activity is seen in both PD and the Parkinson-plus disorders so these scans are not reliable in distinguishing PD from other neurodegenerative causes of parkinsonism.

A CT scan or magnetic resonance imaging (MRI scan) is commonly performed, although these tests do not pick up diffuse metabolic changes associated with dementia in a person that shows no gross neurological problems (such as paralysis or weakness) on neurological exam. CT or MRI may suggest normal pressure hydrocephalus, a potentially reversible cause of dementia, and can yield information relevant to other types of dementia, such as infarction (stroke) that would point at a vascular type of dementia.

The functional neuroimaging modalities of SPECT and PET are more useful in assessing long-standing cognitive dysfunction, since they have shown similar ability to diagnose dementia as a clinical exam and cognitive testing. The ability of SPECT to differentiate the vascular cause (i.e., multi-infarct dementia) from Alzheimer's disease dementias, appears superior to differentiation by clinical exam.

Recent research has established the value of PET imaging using carbon-11 Pittsburgh Compound B as a radiotracer (PIB-PET) in predictive diagnosis of various kinds of dementia, in particular Alzheimer's disease. Studies from Australia have found PIB-PET 86% accurate in predicting which patients with mild cognitive impairment will develop Alzheimer's disease within two years. In another study, carried out using 66 patients seen at the University of Michigan, PET studies using either PIB or another radiotracer, carbon-11 dihydrotetrabenazine (DTBZ), led to more accurate diagnosis for more than one-fourth of patients with mild cognitive impairment or mild dementia.

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.

A physician will initially assess for Parkinson's disease with a careful medical history and neurological examination. People may be given levodopa, with any resulting improvement in motor impairment helping to confirm the PD diagnosis. The finding of Lewy bodies in the midbrain on autopsy is usually considered final proof that the person had PD. The clinical course of the illness over time may reveal it is not Parkinson's disease, requiring that the clinical presentation be periodically reviewed to confirm accuracy of the diagnosis.

Other causes that can secondarily produce parkinsonism are stroke and drugs. Parkinson plus syndromes such as progressive supranuclear palsy and multiple system atrophy must be ruled out. Anti-Parkinson's medications are typically less effective at controlling symptoms in Parkinson plus syndromes. Faster progression rates, early cognitive dysfunction or postural instability, minimal tremor or symmetry at onset may indicate a Parkinson plus disease rather than PD itself. Genetic forms with an autosomal dominant or recessive pattern of inheritance are sometimes referred to as familial Parkinson's disease or familial parkinsonism.

Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process, especially in the early stages of the disease. The most widely known criteria come from the UK Queen Square Brain Bank for Neurological Disorders and the U.S. National Institute of Neurological Disorders and Stroke. The Queen Square Brain Bank criteria require slowness of movement (bradykinesia) plus either rigidity, resting tremor, or postural instability. Other possible causes of these symptoms need to be ruled out. Finally, three or more of the following supportive features are required during onset or evolution: unilateral onset, tremor at rest, progression in time, asymmetry of motor symptoms, response to levodopa for at least five years, clinical course of at least ten years and appearance of dyskinesias induced by the intake of excessive levodopa.

When PD diagnoses are checked by autopsy, movement disorders experts are found on average to be 79.6% accurate at initial assessment and 83.9% accurate after they have refined their diagnosis at a follow-up examination. When clinical diagnoses performed mainly by nonexperts are checked by autopsy, average accuracy is 73.8%. Overall, 80.6% of PD diagnoses are accurate, and 82.7% of diagnoses using the Brain Bank criteria are accurate.

A task force of the International Parkinson and Movement Disorder Society (MDS) has proposed diagnostic criteria for Parkinson’s disease as well as research criteria for the diagnosis of prodromal disease, but these will require validation against the more established criteria.

Several specific diagnostic criteria can be used to diagnose vascular dementia, including the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, the International Classification of Diseases, Tenth Edition (ICD-10) criteria, the National Institute of Neurological Disorders and Stroke criteria, Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, the Alzheimer's Disease Diagnostic and Treatment Center criteria, and the Hachinski Ischemic Score (after Vladimir Hachinski).

The recommended investigations for cognitive impairment include: blood tests (for anemia, vitamin deficiency, thyrotoxicosis, infection, etc.), chest X-Ray, ECG, and neuroimaging, preferably a scan with a functional or metabolic sensitivity beyond a simple CT or MRI. When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging may be used to confirm a diagnosis of multi-infarct dementia in conjunction with evaluations involving mental status examination. In a person already having dementia, SPECT appears to be superior in differentiating multi-infarct dementia from Alzheimer's disease, compared to the usual mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.

The screening blood tests typically include full blood count, liver function tests, thyroid function tests, lipid profile, erythrocyte sedimentation rate, C reactive protein, syphilis serology, calcium serum level, fasting glucose, urea, electrolytes, vitamin B-12, and folate. In selected patients, HIV serology and certain autoantibody testing may be done.

Mixed dementia is diagnosed when people have evidence of Alzheimer's disease and cerebrovascular disease, either clinically or based on neuro-imaging evidence of ischemic lesions.

The symptoms of DLB overlap clinically with those of Alzheimer's disease and Parkinson's disease, but are associated more commonly with the latter. Because of this overlap, early DLB is often misdiagnosed. The overlap of neuropathological and presenting symptoms (cognitive, emotional, and motor) may make an accurate differential diagnosis difficult. In fact, DLB often is confused in its early stages with Alzheimer's disease and/or vascular dementia (multi-infarct dementia). However, while Alzheimer’s disease usually begins gradually, DLB frequently has a rapid or acute onset, with an especially rapid cognitive and physical decline in the first few months. Thus, DLB tends to progress more rapidly than Alzheimer’s disease. Despite the difficulty, a prompt diagnosis is important because of the risks of sensitivity to certain neuroleptic (antipsychotic) medications and because appropriate treatment of symptoms may improve life for both the person with DLB and the person's caregivers.

Dementia with Lewy bodies is distinguished from the dementia that sometimes occurs in Parkinson's disease by the time frame in which dementia symptoms appear relative to Parkinson symptoms. Parkinson's disease with dementia (PDD) would be the diagnosis when the onset of dementia is more than a year after the onset of Parkinsonian symptoms. DLB is diagnosed when cognitive symptoms begin at the same time or within a year of Parkinson symptoms.

Gross examination of the brain may reveal noticeable lesions and damage to blood vessels. Accumulation of various substances such as lipid deposits and clotted blood appear on microscopic views. The white matter is most affected, with noticeable atrophy (tissue loss), in addition to calcification of the arteries. Microinfarcts may also be present in the gray matter (cerebral cortex), sometimes in large numbers.

Although atheroma of the major cerebral arteries is typical in vascular dementia, smaller vessels and arterioles are mainly affected.

The confirmatory diagnosis is made via brain biopsy, however, other tests can be used to help such as MRI, EEG, CT, as well as the physical exam and history

The types of imaging techniques that are most prominently utilized when studying and/or diagnosing CBD are:

- magnetic resonance imaging (MRI)

- single-photon emission computed tomography (SPECT)

- fluorodopa positron emission tomography (FDOPA PET)

Developments or improvements in imaging techniques provide the future possibility for definitive clinical diagnosis prior to death. However, despite their benefits, information learned from MRI and SPECT during the beginning of CBD progression tend to show no irregularities that would indicate the presence of such a neurodegenerative disease. FDOPA PET is used to study the efficacy of the dopamine pathway.

Despite the undoubted presence of cortical atrophy (as determined through MRI and SPECT) in individuals experiencing the symptoms of CBD, this is not an exclusive indicator for the disease. Thus, the utilization of this factor in the diagnosis of CBD should be used only in combination with other clinically present dysfunctions.

Leukoaraiosis (LA) refers to the imaging finding of white matter changes that are common in Binswanger disease. However, LA can be found in many different diseases and even in normal patients, especially in people older than 65 years of age.

There is controversy whether LA and mental deterioration actually have a cause and effect relationship. Recent research is showing that different types of LA can affect the brain differently, and that proton MR spectroscopy would be able to distinguish the different types more effectively and better diagnosis and treat the issue. Because of this information, white matter changes indicated by an MRI or CT cannot alone diagnose Binswanger disease, but can aid to a bigger picture in the diagnosis process. There are many diseases similar to Binswanger's disease including CADASIL syndrome and Alzheimer's disease, which makes this specific type of white matter damage hard to diagnose. Binswanger disease is best when diagnosed of a team by experts including a neurologist and psychiatrist to rule out other psychological or neurological problems. Because doctors must successfully detect enough white matter alterations to accompany dementia as well as an appropriate level of dementia, two separate technological systems are needed in the diagnosing process.

Much of the major research today is done on finding better and more efficient ways to diagnose this disease. Many researchers have divided the MRIs of the brain into different sections or quadrants. A score is given to each section depending on how severe the white matter atrophy or leukoaraiosis is. Research has shown that the higher these scores, the more of a decrease in processing speed, executive functions, and motor learning tasks.

Other researchers have begun using computers to calculate the percentage of white matter atrophy by counting the hyper-intense pixels of the MRI. These and similar reports show a correlation between the amount of white matter alterations and the decline of psychomotor functions, reduced performance on attention and executive control. One recent type of technology is called susceptibility weighted imaging (SWI) which is a magnetic resonance technique which has an unusually high degree of sensitivity and can better detect white matter alternations.

One of the most significant problems associated with CBD is the inability to perform a definitive diagnosis while an individual exhibiting the symptoms associated with CBD is still alive. A clinical diagnosis of CBD is performed based upon the specified diagnostic criteria, which focus mainly on the symptoms correlated with the disease. However, this often results in complications as these symptoms often overlap with numerous other neurodegenerative diseases. Frequently, a differential diagnosis for CBD is performed, in which other diseases are eliminated based on specific symptoms that do not overlap. However, some of the symptoms of CBD used in this process are rare to the disease, and thus the differential diagnosis cannot always be used.

Postmortem diagnosis provides the only true indication of the presence of CBD. Most of these diagnoses utilize the Gallyas-Braak staining method, which is effective in identifying the presence of astroglial inclusions and coincidental tauopathy.

No cure for dementia with Lewy bodies is known. Treatment may offer symptomatic benefit, but remains palliative in nature. Current treatment modalities are divided into pharmaceutical and caregiving.

Binswanger's disease can usually be diagnosed with a CT scan, MRI, and a proton MR spectrography in addition to clinical examination. Indications include infarctions, lesions, or loss of intensity of central white matter and enlargement of ventricles, and leukoaraiosis. Recently a Mini Mental Test (MMT) has been created to accurately and quickly assess cognitive impairment due to vascular dementia across different cultures.

Accurate diagnosis of these Parkinson-plus syndromes is improved when precise diagnostic criteria are used. Since diagnosis of individual Parkinson-plus syndromes is difficult, the prognosis is often poor. Proper diagnosis of these neurodegenerative disorders is important as individual treatments vary depending on the condition. The nuclear medicine SPECT procedure using I-IBZM, is an effective tool in the establishment of the differential diagnosis between patients with PD and Parkinson-plus syndromes.

The progression of the degeneration caused by bvFTD may follow a predictable course. The degeneration begins in the orbitofrontal cortex and medial aspects such as ventromedial cortex. In later stages, it gradually expands its area to the dorsolateral cortex and the temporal lobe. Thus, the detection of dysfunction of the orbitofrontal cortex and ventromedial cortex is important in the detection of early stage bvFTD. As stated above, a behavioural change may occur before the appearance of any atrophy in the brain in the course of the disease. Because of that, image scanning such as MRI can be insensitive to the early degeneration and it is difficult to detect early-stage bvFTD.

In neuropsychology, there is an increasing interest in using neuropsychological tests such as the Iowa gambling task or Faux Pas Recognition test as an alternative to imaging for the diagnosis of bvFTD. Both the Iowa gambling task and the Faux Pas test are known to be sensitive to dysfunction of the orbitofrontal cortex.

Faux Pas Recognition test is intended to measure one’s ability to detect faux pas types of social blunders (accidentally make a statement or an action that offends others). It is suggested that people with orbitofrontal cortex dysfunction show a tendency to make social blunders due to a deficit in self-monitoring. Self-monitoring is the ability of individuals to evaluate their behaviour to make sure that their behaviour is appropriate in particular situations. The impairment in self-monitoring leads to a lack of social emotion signals. The social emotions such as embarrassment are important in the way that they signal the individual to adapt social behaviour in an appropriate manner to maintain relationships with others. Though patients with damage to the OFC retain intact knowledge of social norms, they fail to apply it to actual behaviour because they fail to generate social emotions that promote adaptive social behaviour.

The other test, the Iowa gambling task, is a psychological test intended to simulate real-life decision making. The underlying concept of this test is the somatic marker hypothesis. This hypothesis argues that when people have to make complex uncertain decisions, they employ both cognitive and emotional processes to assess the values of the choices available to them. Each time a person makes a decision, both physiological signals and evoked emotion (somatic marker) are associated with their outcomes and it accumulates as experience. People tend to choose the choice which might produce the outcome reinforced with positive stimuli, thus it biases decision-making towards certain behaviours while avoiding others. It is thought that somatic marker is processed in orbitofrontal cortex.

The symptoms observed in bvFTD are caused by dysfunction of the orbitofrontal cortex, thus these two neuropsychological tests might be useful in detecting the early stage bvFTD. However, as self-monitoring and somatic marker processes are so complex, it likely involves other brain regions. Therefore, neuropsychological tests are sensitive to the dysfunction of orbitofrontal cortex, yet not specific to it. The weakness of these tests is that they do not necessarily show dysfunction of the orbitofrontal cortex.

In order to solve this problem, some researchers combined neuropsychological tests which detect the dysfunction of orbitofrontal cortex into one so that it increases its specificity to the degeneration of the frontal lobe in order to detect the early-stage bvFTD. They invented the Executive and Social Cognition Battery which comprises five neuropsychological tests.

- Iowa gambling task

- Faux Pas test

- Hotel task

- Mind in the Eyes

- Multiple Errands Task

The result has shown that this combined test is more sensitive in detecting the deficits in early bvFTD.

Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy can be either bilateral or asymmetric. Registration of images at different points of time (e.g., one year apart) can show evidence of atrophy that otherwise (at individual time points) may be reported as normal. Many research groups have begun using techniques such as magnetic resonance spectroscopy, functional imaging and cortical thickness measurements in an attempt to offer an earlier diagnosis to the FTD patient. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate the disease from Alzheimer's disease. The PET scan in Alzheimer's disease classically shows biparietal hypometabolism. Meta-analyses based on imaging methods have shown that frontotemporal dementia mainly affects a frontomedial network discussed in the context of social cognition or 'theory of mind'. This is entirely in keeping with the notion that on the basis of cognitive neuropsychological evidence, the ventromedial prefrontal cortex is a major locus of dysfunction early on in the course of the behavioural variant of frontotemporal degeneration. The language subtypes of frontotemporal lobar degeneration (semantic dementia and progressive nonfluent aphasia) can be regionally dissociated by imaging approaches "in vivo".

The confusion between Alzheimer's and FTD is justifiable due to the similarities between their initial symptoms. Patients do not have difficulty with movement and other motor tasks. As FTD symptoms appear, it is difficult to differentiate between a diagnosis of Alzheimer's disease and FTD. There are distinct differences in the behavioral and emotional symptoms of the two dementias, notably, the blunting of emotions seen in FTD patients. In the early stages of FTD, anxiety and depression are common, which may result in an ambiguous diagnosis. However, over time, these ambiguities fade away as this dementia progresses and defining symptoms of apathy, unique to FTD, start to appear.

Recent studies over several years have developed new criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD). Six distinct clinical features have been identified as symptoms of bvFTD.

1. Disinhibition

2. Apathy/Inertia

3. Loss of Sympathy/Empathy

4. Perseverative/compulsive behaviors

5. Hyperorality

6. Dysexecutive neuropsychological profile

Of the six features, three must be present in a patient to diagnose one with possible bvFTD. Similar to standard FTD, the primary diagnosis stems from clinical trials that identify the associated symptoms, instead of imaging studies. The above criteria are used to distinguish bvFTD from disorders such as Alzheimer's and other causes of dementia. In addition, the new criteria allow for a diagnostic hierarchy distinguished possible, probable, and definite bvFTD based on the number of symptoms present.

For diagnostic purposes, magnetic resonance imaging (MRI) and ([18F]fluorodeoxyglucose) positron emission tomography (FDG-PET) are applied. They measure either atrophy or reductions in glucose utilization. The three clinical subtypes of frontotemporal lobar degeneration, frontotemporal dementia, semantic dementia and progressive nonfluent aphasia, are characterized by impairments in specific neural networks. The first subtype with behavioral deficits, frontotemporal dementia, mainly affects a frontomedian network discussed in the context of social cognition. Semantic dementia is mainly related to the inferior temporal poles and amygdalae; brain regions that have been discussed in the context of conceptual knowledge, semantic information processing, and social cognition, whereas progressive nonfluent aphasia affects the whole left frontotemporal network for phonological and syntactical processing.

Diagnosis of MSA can be challenging because there is no test that can definitively make or confirm the diagnosis in a living patient. Clinical diagnostic criteria were defined in 1998 and updated in 2007. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult.

Both MRI and CT scanning frequently show a decrease in the size of the cerebellum and pons in those with cerebellar features. The putamen is hypodense on T2-weighted MRI and may show an increased deposition of iron in Parkinsonian form. In cerebellar form, a "hot cross" sign has been emphasized; it reflects atrophy of the pontocereballar fibers that manifest in T2 signal intensity in atrophic pons.

A definitive diagnosis can only be made pathologically on finding abundant glial cytoplasmic inclusions in the central nervous system.

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 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.

Parkinson-plus syndromes are usually more rapidly progressive and less likely to respond to antiparkinsonian medication than PD. However, the additional features of the diseases may respond to medications not used in PD.

Current therapy for Parkinson-plus syndromes is centered around a multidisciplinary treatment of symptoms.

These disorders have been linked to pesticide exposure.

MRI is often done to diagnose PSP. MRI may show atrophy in the midbrain with preservation of the pons giving a "hummingbird" sign appearance.

PSP is frequently misdiagnosed as Parkinson's disease because of the slowed movements and gait difficulty, or as Alzheimer's disease because of the behavioral changes. It is one of a number of diseases collectively referred to as Parkinson plus syndromes. A poor response to levodopa along with symmetrical onset can help differentiate this disease from PD. Also, patients with the Richardson variant tend to have an upright or arched-back posture as opposed to the stooped-forward posture of other Parkinsonian disorders, although PSP-Parkinsonism (see below) may show the stooped posture. Early falls are characteristic, especially with Richardson-syndrome.