Alzheimer’s disease can present commonly in the typical form but can also present in atypical way. In clinical practice, it can be difficult to distinguish behavioural variant of frontotemporal dementia (bvFTD) and the frontal variant of Alzheimer’s disease (fvAD). The author presents a scenario of fv-AD. Good clinical interview, neuropsychological testing, brain scanning, a good response to cholinesterase inhibitors and biomarkers can help the diagnosis.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, typically characterized by progressive episodic memory loss at onset, followed by impairment in other cognitive domains such as language and visuospatial deficits. In Alzheimer’s disease (AD) an amnestic syndrome is the most common presentation; however, atypical variants have been recognized. The International Working Group diagnostic criteria for AD (IWG-2 criteria) [1], proposed that specific phenotypes of atypical AD include posterior cortical atrophy, logopenic primary progressive aphasia, Down's syndrome variant, and frontal variant of AD (fvAD). Also, executive dysfunction is a common presentation of neurodegenerative disorders including Alzheimer’s disease and Frontotemporal dementia. Palmer et al. [2] suggested that impairment of the executive functions can be early characteristics of AD, with high prognostic value. In clinical practice it can be difficult to distinguish behavioural variant of frontotemporal dementia (bvFTD) and the frontal variant of Alzheimer’s disease (fvAD) [3]. FvAD can also be confounded by vascular pathology (small and large vessel vasculopathy) affecting frontal lobes and its networks. This diagnostic challenge can have an impact on the management and counselling of these patients.
This case scenario is imaginative summarising two cases presented to memory clinic.
Vic is a 68 year’s old retired gentleman who was referred to memory clinic by his GP complaining of a two year history of gradually progressing short-term memory and recall problems. Vic left school at age 15, went to College and worked for the local council. He is married with five children. He never smoked and occasionally drinks alcohol. He has a past history of asthma and osteoarthritis. There is no reported family history of dementia.
His family reported short-term memory problem, poor recall, and some personality changes including apathy, agitation and irritability, weight loss and some executive dysfunction.
When assessed, Vic reported word finding difficulty, losing the flow of conversation, forgetting names, he forgot how to use the mobile phone. He tends to buy the same items when shopping and does not recognise some of the food items including vegetables.
On mental state examination, there was no evidence of functional mental illness or parkinsonian symptoms. On cognitive testing, Vic scored 61/100 on the ACE-III with significant drop in memory, fluency and language. There was evidence of paraphasia, preservative behaviour and executive dysfunction.
The dementia blood screening tests were within normal limits.
CT head scan showed focal dilatation of the temporal horn in the left lateral ventricle associated with focal atrophy of the left temporal lobe.
Vic responded well to Cholinesterase Inhibitors.
The case represents evidence of both temporal and frontal lobe involvements. Frontal variant-AD was described by Johnson JK et al. [4] and compared with the typical AD group, the frontal AD group performed significantly worse on 2 tests of frontal lobe functioning and on the Wechsler Adult Intelligence Scale–Revised Block Design test.
Clinically fv-AD can be divided into behavioural or dysexecutive subtypes and in both subtypes executive functions are impaired. Patients may show semantic and phonemic paraphasia, agitation/irritability, apathy, compulsive or preservative behaviours, delusions and weight loss due to depression. Neuropathological profiles showed low Aβ42 and high levels of T-tau and P-Tau in CSF while brain scans show temporoparietal atrophy more than frontal lobe atrophy [5].
Clinical heterogeneity is one of the characteristics of Alzheimer's disease and clinicians should be aware of atypical frontal or dysexecutive presentation, although the underlying factors are still unknown.
It is not always easy to differentiate fv-AD from bv-FTD. Good clinical interview, neuropsychological testing, and brain scanning can help the diagnosis. A good response to cholinesterase inhibitors is another clue for fv-AD. However, if clinicians are in doubt, biomarkers such as positive APOE E4 allele, and CSF AB42 and tau are sensitive for AD. The author is of the view that more research is needed to help identify initial symptoms, risk factors, genetics and prognosis of fv-AD.
- Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, et al. (2014). Advancing research diagnostic criteria for Alzheimer's disease: The IWG-2 criteria. Lancet Neurol 13: 614–629. [Crossref]
- Palmer K, Lupo F, Perri R, Salamone G, Fadda L, et al. (2011) Predicting disease progression in Alzheimer’s disease: the role of neuropsychiatric syndromes on functional and cognitive decline. J Alzheimers Dis 24: 35-345. [Crossref]
- Sawyer RP, Rodriguez-Porcel F, Hagen M, Shatz R, Espay AJ, et al. (2017) Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road. J Clin Mov Disord 4: 2. [Crossref]
- Johnson JK, Head E, Kim R, Starr A, Cotman CW (1999) Clinical and Pathological Evidence for a Frontal Variant of Alzheimer Disease. Arch Neurol 56: 1233-1239. [Crossref]
- de Souza LC, Bertoux M, Funkiewiez A, Samri D, Azuar C, et al. (2013) Frontal presentation of Alzheimer's disease: a series of patients with biological evidence by CSF biomarkers. Dement Neuropsychol 7: 66-74. [Crossref]
