Argyrophilic grain disease – Brazilian Aging Brain Study Group description

This interesting review of argyrophilic grain disease (AGD) was recently published by the Brazilian Aging Brain Study Group.  (One of the leaders of the Brazilian study is now at UCSF.)  The full article is available at no charge here:

The abstract notes:

Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians. The most common AGD manifestation is slowly progressive amnestic mild cognitive impairment, accompanied by a high prevalence of neuropsychiatric symptoms. … AGD is frequently seen together with Alzheimer’s disease-type pathology or in association with other neurodegenerative diseases. 

Generally, clinical symptoms of AGD are memory impairment (like Alzheimer’s) and neuropsychiatric symptoms.  The mild cognitive impairment progresses very slowly, in most cases.  Common neuropsychiatric symptoms include personality changes (rudeness, stubbornnes, egocentric behavior, disinhibition, obsession, apathy) and depression.  The neuropsychiatric symptoms may pre-date the memory impairment.  Given these symptoms, common clinical diagnoses are Alzheimer’s, frontotemporal dementia, and progressive supranuclear palsy.

The article notes:

A study comparing Parkinson’s disease patients with and without AGD, and studies showing a high prevalence of AGD in individuals with late-onset schizophrenia and delusional disorders, corroborate the association of AGD with psychiatric symptoms.  Asaoka et al. reported an AGD case exhibiting delusions and hallucinations at clinical presentation.  A few reports implicate AGD as the underlying condition in patients featuring clinical frontotemporal dementia. In such cases, AGD pathology is widespread in the brain, as opposed to the majority of AGD cases where involvement is restricted to limbic structures.

There are no clinical diagnostic criteria for diagnosing someone with AGD during life.  The article addresses this by noting, “At any rate, AGD is virtually unknown to the clinical community because most cases do not present any known distinctive clinical symptoms.”  Confusingly for clinicians, AGD can be present in those with cognitive impairment or neuropsychiatric symptoms.  It is a postmortem diagnosis.

Pathologically, we at Brain Support Network see AGD co-occurring with other neurodegenerative diseases, especially other tauopathies such as progressive supranuclear palsy (PSP).

AGD commonly occurs in older people. But AGD can be seen in younger people.  The article states,  “In the series of the Brain Bank of the Brazilian Aging Brain Study Group, 6.7% of individuals aged between 50 and 60 had AGD.”

There is some thought that the presence of AGD may ward of the development of other pathologies, such as Alzheimer’s Disease.  The authors note:

The reasons why AGD does not develop with prominent clinical features have yet to be clarified. Recent evidence of lack of tau acetylation in AGD suggest a protective role of this entity against spread of other neurodegenerative conditions, particularly Alzheimer’s disease and is a hypothesis currently being investigated.

This review article adds greatly to our understanding of AGD.