February Research Wrap: Logopenic Primary Progressive Aphasia

research 5This month, we have just made it to post our Research Wrap for February, but with a mega effort by Dr Shibley Rahman in writing this today, we have made it! Sincere thanks for this ongoing support for our members Shibley.

Many of our members have PPA or LPPA, and this particular article will be particularly enlightening.

Living beyond a diagnosis of logopenic PPA requires a multi-pronged approach

One of the most important questions for persons receiving a diagnosis is the issue of in what way the diagnosis benefits him or her.

It is said that one of the strongest attractions of receiving a correct diagnosis of diagnosis is that you can plan ahead. That is not to ‘pack up your bags’ and be encouraged to ‘give up’, but to look ahead to living beyond a diagnosis of dementia. See Kate Swaffer’s excellent book “What the hell happened to my brain?” (Swaffer, 2016), a testament to this, and worth more than a million charities or think tanks.

  1. What is PPA? What is LPPA?

There’s also the issue of how exactly knowing the type of dementia can possibly help. Common reasons include having a coherent explanation for symptoms, and having some help.

The very specific type of dementia known as “logopenic primary progressive aphasia” (“LPPA”) is a form of dementia whose hallmark is a progressive loss of function. It is due to the loss of function of parts of the brain involved in speech and language. It comes under the umbrella of dementias called the frontotemporal dementias, under the class of primary progressive aphasias (“PPA”), first described in the modern literature by Mesulam (reviewed by Henry and Gorno-Tempini, 2010, responsible themselves for putting LPPA ‘on the map’).

Concentrating on the language to the other needs of a person with LPPA is wrong, however. From the Mayo Clinic, Tarun Singh and colleagues (2015) reported that often appetite and mood changes accompanied early progressive primary aphasia.

The centrepiece of the cognitive problem in “logopenic PPA” (LPPA) is a problem with word finding. In small talk, speech is pretty fluent, but tends to break into mispronounciations and word-finding pauses when more difficult or more precise words are needed. The naming of objects can become impaired, and replaced in speech by phrases such as “you know what I mean”.

Logopenic PPA is rarer, in terms of the numbers of people involved, than other forms of dementia, but throws into focus crucial questions about how we view dementia. And research in this area in the last five or six years has been rapid. It also throws into question how we can best support people living beyond a diagnosis. 

  1. Is LPPA in fact a form of Alzheimer’s disease?

The pattern of pauses in speech can be helpful in working out the neural networks which go wrong in LPPA. We know this now from recent work by Mack and colleagues (2015). There’s been a question as to which parts of the brain are involved. Whilst there might have seemed to be a very focal start to the underlying disease from previous research, such as the left temporal and inferior parietal parts of the brain, very recent work published from Cristian Leyton, Anna Britton, John R. Hodges, Glenda M. Halliday, and Jillian J. Krill recently (2016) found all of their patients had quite extensive Alzheimer’s changes extending to ‘deep cortical areas’ of brain. This of course is truly fascinating.

Indeed, Stephanie Awad and Amer Awad (2011) had earlier mooted whether one of their patients had presented with LPPA but in fact as a “precursor to Alzheimer’s disease”. The patient is a 54-year-old left-handed Caucasian lady who had been referred to their centre for evaluation of speech difficulties. The patient noted a gradually progressing speech problem about two years prior to her presentation. Her main difficulties were related to word finding and inability to express herself very well with frequent pauses.

The authors correctly concluded, “The early symptoms are very subtle and require a high index of suspicion. Healthcare providers need to be aware of this entity and other entities that present with subtle cognitive abnormalities.” (Awad and Awad, 2011)

A series from Japan (Funayama et al., 2013) then notably suggested that some patients with LPPA develop an atypical type of dementia with apraxia and semantic memory deficits, suggesting that these cases should be classified as a type of early-onset Alzheimer’s disease.

Taken as a whole, a recent neuroimaging study by Matias-Guiu and colleagues (2015) supported the notion that PPA is a heterogeneous clinical syndrome, which may progress into various forms of diseases with time.

  1. Is a pharmacological treatment for LPPA possible?

This leads us to the interesting position that the cluster of cognitive symptoms clinically might lead to a particular diagnostic label, such as logopenic PPA, but ultimately might have a common underlying disease process. This is similar to the position Pharma was in on how antidepressant drugs were said to be effective, irrespective of the exact neurobiological causes of unipolar depression.

The rôle of abnormal levels of tau and amyloid in the brains of people living with dementia remains under scrutiny, and rightly so. What is becoming quite clear though is that they may not be specific to what clinicians view as Alzheimer’s disease. This of course offers a window of opportunity for Pharma medically to ‘cure dementias’, in the sense that the exact diagnostic label of the dementia may not be quite as important as first thought.

Indeed, in a short report which has only just been published (Pascual and Masdeu, 2016), high uptake of proteins binding to tau and amyloid (with variable areas of metabolism) have been reported for a 57-year old lady thought to have a 8 year history of LPPA.

Fang and colleagues (Fang et al., 2014) in a remarkable paper for Nature Communications had found that toxic amyloid oligomers could indeed build up in “frontotemporal lobar dementia-TDP” patients. Nonetheless, it is possible that some medications may be efficacious for symptomatic treatment for LPPA, even if not arresting the disease.

Tiffany Chow (Chow et al., 2011) in work from Toronto has been evaluating critically the possible beneficial effects of a medication called memantine. At roughly the same time, Nancy Johnson and colleagues (Johnson et al., 2010) reported on a trend to a significant effect of memantine in a double-blind placebo-controlled trial with 18 PPA subjects. Persons living with PPA will always be guided by their own responsible physicians as to what might possibly work best for them. Memantine is of course not “the only fruit”.

  1. Conclusion – but there’s clearly a need to look ‘beyond drugs’.

Any modern critique of dementia needs now to look ‘beyond drugs’ (Power, 2010).

Looking beyond drugs, as speech and language are such critical features of logopenic PPA, it makes sense for a speech and language specialist to carry out a detailed assessment of speech and language.

Approaches to intervene might include skills to enhance word-retrieval abilities, or alternative communication strategies. This approach is consistent with reablement for a disability, akin to a crutch for a broken leg.

But LPPA shows graphically it would be wrong to put all your eggs in the medical basket. Living beyond a diagnosis requires a multi-pronged approach.

[Disclaimer: This article is not to be used in any way, or construed as, medical advice. This of necessity is true for all posts and information on the Dementia Alliance International blog.] 

References

Awad SM, Awad AM. (2011) A middle-aged woman with logopenic progressive aphasia as a precursor of Alzheimer’s disease: case report and review of the literature. Case Rep Neurol Med. 450301. doi: 10.1155/2011/450301. Epub 2011 Sep 29.

Chow TW, Graff-Guerrero A, Verhoeff NP, Binns MA, Tang-Wai DF, Freedman M, Masellis M, Black SE, Wilson AA, Houle S, Pollock BG. (2011) Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia. Neuropsychiatr Dis Treat. 7:415-24. doi: 10.2147/NDT.S22635. Epub 2011 Jul 13.

Fang YS, Tsai KJ, Chang YJ, Kao P, Woods R, Kuo PH, Wu CC, Liao JY, Chou SC, Lin V, Jin LW, Yuan HS, Cheng IH, Tu PH, Chen YR. (2014) Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients. Nat Commun. Sep 12;5:4824. doi: 10.1038/ncomms5824.

Funayama M, Nakagawa Y, Yamaya Y, Yoshino F, Mimura M, Kato M. (2013) Progression of logopenic variant primary progressive aphasia to apraxia and semantic memory deficits. BMC Neurol. Nov 1;13:158. doi: 10.1186/1471-2377-13-158.

Henry ML, Gorno-Tempini ML. (2010) The logopenic variant of primary progressive aphasia. Curr Opin Neurol. Dec;23(6):633-7. doi: 10.1097/WCO.0b013e32833fb93e.

Johnson NA, Rademaker A, Weintraub S, Gitelman D, Wienecke C, Mesulam M. (2010) Pilot trial of memantine in primary progressive aphasia. Alzheimer Dis Assoc Disord. Jul-Sep;24(3):308. doi: 10.1097/WAD.0b013e3181cf468d.

Leyton CE, Britton AK, Hodges JR, Halliday GM, Kril JJ. (2016) Distinctive pathological mechanisms involved in primary progressive aphasias. Neurobiol Aging. Feb;38:82-92. doi: 10.1016/j.neurobiolaging.2015.10.017. Epub 2015 Oct 26.

Mack JE, Chandler SD, Meltzer-Asscher A, Rogalski E, Weintraub S, Mesulam MM, Thompson CK. (2015) What do pauses in narrative production reveal about the nature of word retrieval deficits in PPA? Neuropsychologia. Oct;77:211-22. doi: 10.1016/j.neuropsychologia.2015.08.019. Epub 2015 Aug 20.

Matias-Guiu JA, Cabrera-Martín MN, Moreno-Ramos T, García-Ramos R, Porta-Etessam J, Carreras JL, Matías-Guiu J. (2015) Clinical course of primary progressive aphasia: clinical and FDG-PET patterns. J Neurol. Mar;262(3):570-7. doi: 10.1007/s00415-014-7608-0. Epub 2014 Dec 10.

Pascual B, Masdeu JC. (2016) Tau, amyloid, and hypometabolism in the logopenic variant of primary progressive aphasia. Neurology. Feb 2;86(5):487-8. doi: 10.1212/WNL.0000000000002340.

Power, G.A. (2010) Dementia beyond drugs: changing the culture of care, Baltimore: Health Professions Press.

Singh TD, Duffy JR, Strand EA, Machulda MM, Whitwell JL, Josephs KA. (2015) Neuropsychiatric symptoms in primary progressive aphasia and apraxia of speech. Dement Geriatr Cogn Disord. 39(3-4):228-38. doi: 10.1159/000369062. Epub 2015 Jan 21.

Swaffer, K. (2016) What the hell happened to my brain? London: Jessica Kingsley Publishers.