Currently, the specific causes for PPA and other degenerative brain disease similar to PPA are unknown. Autopsies have revealed a variety of brain abnormalities in people who had PPA. These autopsies, as well as imaging techniques such as CT scans, MRI, EEG, single photon emission computed tomography (SPECT), and positron emission tomography (PET), have generally revealed abnormalities to be almost exclusively in the left hemisphere.

Due to the progressive, continuous nature of the disease, improvement over time seldom occurs in patients with PPA as it often does in patients with aphasias caused by trauma to the brain.

In terms of medical approaches to treating PPA, there are currently no drugs specifically used for patients with PPA, nor are there any specifically designed interventions for PPA. A large reason for this is the limited research that has been done on this disease. However, in some cases, patients with PPA are prescribed the same drugs Alzheimer's patients are normally prescribed.

The primary approach to treating PPA has been with behavioral treatment, with the hope that these methods can provide new ways for patients to communicate in order to compensate for their deteriorated abilities. Speech therapy can assist an individual with strategies to overcome difficulties. There are three very broad categories of therapy interventions for aphasia: restorative therapy approaches, compensatory therapy approaches, and social therapy approaches. Rapid and sustained improvement in speech and dementia in a patient with primary progressive aphasia utilizing off-label perispinal etanercept, an anti-TNF treatment strategy also used for Alzheimer's, has been reported. A video depicting the patient's improvement was published in conjunction with the print article. These findings have not been independently replicated and remain controversial.

There is currently no known curative treatment for SD. The average duration of illness is 8–10 years, and its progression cannot be slowed. Progression of SD can lead to behavioral and social difficulties, thus supportive care is essential for improving quality of life in SD patients as they grow more incomprehensible.

Continuous practice in lexical learning has been shown to improve semantic memory in SD patients.

SD has no known preventative measures.

Imaging studies have shown differing results which probably represents the heterogeneity of language problems than can occur in PNFA. However, classically atrophy of left perisylvian areas is seen.

Comprehensive meta-analyses on MRI and FDG-PET studies identified alterations in the whole left frontotemporal network for phonological and syntactical processing as the most consistent finding. Based on these imaging methods, progressive nonfluent aphasia can be regionally dissociated from the other subtypes of frontotemporal lobar degeneration, frontotemporal dementia and semantic dementia.

The diagnosis of frontal lobe disorder can be divided into the following three categories:

- Clinical history

Frontal lobe disorders may be recognized through a sudden and dramatic change in a person's personality, for example with loss of social awareness, disinhibition, emotional instability, irritability or impulsiveness. Alternatively the disorder may become apparent because of mood changes such as depression, anxiety or apathy.

- Examination

On mental state examination a person with frontal lobe damage may show speech problems, with reduced verbal fluency. Typically the person is lacking in insight and judgment, but does not have marked cognitive abnormalities or memory impairment (as measured for example by the mini-mental state examination). With more severe impairment there may be echolalia or mutism. Neurological examination may show primitive reflexes (also known as frontal release signs) such as the grasp reflex. Akinesia (lack of spontaneous movement) will be present in more severe and advanced cases.

- Further investigation

A range of neuropsychological tests are available for clarifying the nature and extent of frontal lobe dysfunction. For example, concept formation and ability to shift mental sets can be measured with the Wisconsin Card Sorting Test, planning can be assessed with the Mazes subtest of the WISC. Individuals with Pick's disease will show frontal cortical atrophy on MRIs. Frontal impairment due to head injuries, tumours or cerebrovascular disease will also be apparent on brain imaging.

There is no curative treatment for this condition. Supportive management is helpful.

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

Semantic dementia (SD), also known as semantic variant primary progressive aphasia (svPPA), is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains. However, the most common presenting symptoms are in the verbal domain (with loss of word meaning). SD is one of the three canonical clinical syndromes associated with frontotemporal lobar degeneration (FTLD), with the other two being frontotemporal dementia and progressive nonfluent aphasia. SD is a clinically defined syndrome, but is associated with predominantly temporal lobe atrophy (left greater than right) and hence is sometimes called temporal variant FTLD (tvFTLD). SD is one of the three variants of Primary Progressive Aphasia (PPA), which results from neurodegenerative disorders such as FTLD or Alzheimer's disease. It is important to note the distinctions between Alzheimer’s Disease and Semantic dementia with regard to types of memory affected. In general, Alzheimer’s Disease is referred to as disorder affecting mainly episodic memory, defined as the memory related to specific, personal events distinct for each individual. Semantic dementia generally affects semantic memory, which refers to long-term memory that deals with common knowledge and facts.3

It was first described by Arnold Pick in 1904 and in modern times was characterized by Professor Elizabeth Warrington in 1975, but it was not given the name semantic dementia until 1989. The clinical and neuropsychological features, and their association with temporal lobe atrophy were described by Professor John Hodges and colleagues in 1992.

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.

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.

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.

In terms of treatment for frontal lobe disorder, general supportive care is given, also some level of supervision could be needed. The prognosis will depend on the cause of the disorder, of course. A possible complication is that individuals with severe injuries may be disabled, such that, a caregiver may be unrecognizable to the person.

Another aspect of treatment of frontal lobe disorder is speech therapy. This type of therapy might help individuals with symptoms that are associated with aphasia and dysarthria.

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.

Currently, there is no cure for FTD. Treatments are available to manage the behavioral symptoms. Disinhibition and compulsive behaviors can be controlled by selective serotonin reuptake inhibitors (SSRIs). Although Alzheimer's and FTD share certain symptoms, they cannot be treated with the same pharmacological agents because the cholinergic systems are not affected in FTD.

Because FTD often occurs in younger people (i.e. in their 40's or 50's), it can severely affect families. Patients often still have children living in the home. Financially, it can be devastating as the disease strikes at the time of life that often includes the top wage-earning years.

Personality changes in individuals with FTD are involuntary. Managing the disease is unique to each individual, as different patients with FTD will display different symptoms, sometimes of rebellious nature.

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.

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.

Phonagnosia (from Ancient Greek φωνή "phone", "voice" and γνῶσις "gnosis", "knowledge") is a type of agnosia, or loss of knowledge, that involves a disturbance in the recognition of familiar voices and the impairment of voice discrimination abilities in which the affected individual does not suffer from comprehension deficits. Phonagnosia is an auditory agnosia, an acquired auditory processing disorder resulting from brain damage, other auditory agnosias include cortical deafness and auditory verbal agnosia also known as pure word deafness.

Since people suffering from phonagnosia do not suffer from aphasia, it is suggested that the structures of linguistic comprehension are functionally separate from those of the perception of the identity of the speaker who produced it.

Phonagnosia is the auditory equivalent of prosopagnosia. Unlike Prosopagnosia, investigations of phonagnosia have not been extensively pursued. Phonagnosia was first described by a study by Van Lancker and Cantor in 1982. The subjects in this study were asked to identify which of four names or faces matched a specific famous voice. The subjects could not complete the task. Since then, there have been a couple studies done on patients with phonagnosia. The clinical and radiologic findings with computerized tomographic scans cat scan in these cases suggest that recognition of familiar voices is impaired by damage to the inferior and parietal regions of the right hemisphere while voice discrimination is impaired by temporal lobe damage of either hemisphere. These studies have also shown evidence for a double dissociation between voice recognition and voice discrimination. Some patients will perform normally on the discrimination tasks but poorly on the recognition tasks; whereas the other patients will perform normally on the recognition tasks but poorly on the discrimination tasks. Patients did not perform poorly on both tasks.

Associative phonagnosia is a form of phonagnosia that develops with dementia or other focal neurodegenerative disorders. Some research has led to questions of other impairments in phonagnosics. Recently, studies have shown that phonagnosics also have trouble in recognizing the sounds of familiar instruments. As it is with voices, they also show deficiency in distinguishing between sounds from different instruments. Although the disability is shown, phonagnosics are much less affected in this area of sound discrimination. In distinguishing voices, it is a complete agnosia, but this is not the case for musical instrument sounds, as they can correctly identify some of them. Controversy arises in that not all phonagnosics exhibit these symptoms, and so not all researchers agree that it should be attributed to the damage suffered that causes phonagnosia. Much debate has arisen over the fact that it seems that separate areas of the brain are utilized to handle information from language and music. This has led some researchers to skeptically consider this impairment as a clear symptom of the disorder. Again, more research is needed to create a clearer conclusion.

An interesting attribute that phonagnosics possess is that they can correctly detect emotions in voices when someone talks to them. They can also correctly match an emotion with a facial expression. Although surprising, this finding is sensible because it is known and well agreed upon that the limbic system, involved in expressing emotions and detecting emotions of others, is a separate system within the brain. The limbic system is made up of several brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix.

Presently, there is no therapy or treatment for phonagnosia. Clearly, more research is needed to accomplish the feat of developing treatment for the disorder. The lack of treatment stems from the lack of knowledge about the disorder. Increased research will reveal vital information needed to formulate effective treatments and therapies.

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.

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.

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.

The existence of alcohol-related dementia is widely acknowledged but not often used as a diagnosis, due to a lack of widely accepted, non-subjective diagnostic criteria; more research is needed. Criteria for alcohol-induced persistent dementia in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) include the following:

There are problems with DSM diagnostic criteria, however. Firstly, they are vague and subjective. Furthermore, the criteria for diagnosis of dementia were inspired by the clinical presentation of Alzheimer's disease and are poorly adapted to the diagnosis of other dementias. This has led to efforts to develop better diagnostic models.

Oslin (Int J Geriatr Psychiatry 1998) proposed alternative clinical diagnostic criteria which were validated. The criteria include a clinical diagnosis of dementia at least 60 days after last exposure to alcohol, significant alcohol use (i.e. minimum 35 standard drinks/week for males and 28 for women) for more than 5 years, and significant alcohol use occurring within 3 years of the initial onset of cognitive deficits. Oslin proposed the new and refined diagnostic criteria for Alcohol Related Dementia because he hoped that the redefined classification system would bring more awareness and clarity to the relationship between alcohol use and dementia.

Oslin's proposed classification of ARD:

- "Definite" Alcohol Related Dementia

At the current time there are no acceptable criteria to definitively define Alcohol Related Dementia.

- "Probable" Alcohol Related Dementia

Agnosia is the inability to recognize certain objects, persons or sounds. Agnosia is typically caused by damage to the brain (most commonly in the occipital or parietal lobes) or from a neurological disorder. Treatments vary depending on the location and cause of the damage. Recovery is possible depending on the severity of the disorder and the severity of the damage to the brain. Many more specific types of agnosia diagnoses exist, including: associative visual agnosia, astereognosis, auditory agnosia, auditory verbal agnosia, prosopagnosia, simultanagnosia, topographical disorientation, visual agnosia etc.

Anosodiaphoria is a condition in which a person who suffers disability due to brain injury seems indifferent to the existence of their handicap. Anosodiaphoria is specifically used in association with indifference to paralysis. It is a somatosensory agnosia, or a sign of neglect syndrome. It might be specifically associated with defective functioning of the frontal lobe of the right hemisphere.

Joseph Babinski first used the term anosodiaphoria in 1914 to describe a disorder of the body schema in which patients verbally acknowledge a clinical problem (such as hemiparesis) but fail to be concerned about it. Anosodiaphoria follows a stage of anosognosia, in which there may be verbal, explicit denial of the illness, and after several days to weeks, develop the lack of emotional response. Indifference is different from denial because it implies a lack of caring on the part of the patient whom otherwise acknowledges his or her deficit.

Indifference to illness may have an adverse impact on a patient's engagement in neurological rehabilitation, cognitive rehabilitation and physical rehabilitation. Patients are not likely to implement rehabilitation for a condition about which they are indifferent. Although anosognosia often resolves in days to weeks after stroke, anosodiaphoria often persists. Therefore, the therapist has to be creative in their rehabilitation approach in order to maintain the interest of the patient.