- Open Access
Role of neuroimaging in multidisciplinary approach towards Non-Alzheimer’s dementia
© The Author(s) 2015
- Received: 21 October 2014
- Accepted: 8 July 2015
- Published: 24 July 2015
Dementia is defined as chronic deterioration of intellectual function and cognitive skills significant enough to interfere with the ability to perform daily activities. Recent advances in the treatment of dementia have renewed interest in the use of various neuroimaging techniques that can assist in the diagnosis and differentiation of various subtypes. Neuroimaging and computational techniques have helped the radiological community to monitor disease progression of various neurodegenerative conditions presenting with dementia, such as Alzheimer disease, frontotemporal lobe dementia (FTLD), progressive supranuclear palsy (PSP) and multisystem atrophy-cerebellar variant (MSA-C), and their response to newer therapies. Prompt identification of treatable or reversible forms of dementia, such as tumours, subdural haemorrhage and intracranial dAVF, is crucial for the effective management of these conditions. It is also prudent to recognize the imaging spectrum of metabolic, infective and autoimmune diseases with rapidly progressing dementia, such as methanol toxicity, central pontine myelinolysis (CPM), delayed post hypoxic leukoencephalopathy (DPHL), HIV, Creutzfeldt-Jakob Disease (CJD), Sjogren's syndrome, multiple sclerosis (MS), radiation necrosis and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), which are difficult to treat and often require palliative care. This pictorial review emphasizes various non-Alzheimer’s dementia entities and discusses their imaging highlights.
• Non Alzheimer’s dementia constitutes a broad spectrum of conditions.
• Neuroimaging plays an important role in differentiating treatable from irreversible dementia.
• Neuroimaging is often non-specific in early stages of neurodegenerative conditions with dementia.
• Neuroimaging plays an important role in the multimodal approach towards management of dementia.
Dementia is a disorder characterized by global impairment in cognition, social and occupational functioning severe enough to interfere with daily functioning and quality of life. Various studies have confirmed an exponential increase in dementia with age and a higher prevalence in older females . Overall, dementia has a significant burdening impact onsocio-economic status and the health care system.
Alzheimer disease (AD) is the most common cause of primary dementia, constituting 60 % of all cases. Vascular dementia is the second most common form of dementia, which often coexists with AD. There are various other non-Alzheimer conditions, which may present with cognitive impairments and can be divided into the broad categories of neurodegenerative, inflammatory/infective, metabolic/genetic and miscellaneous. This pictorial review emphasizes the role of neuroimaging in evaluating various causes of non-Alzheimer’s dementia. We also highlight conditions with reversible dementia, where neuroimaging plays a significant role in management.
Vascular dementia (VaD)
Binswanger and Alzheimer first described VaD and recognized the role of multiple infarctions and chronic ischemia in its etiopathogenesis. VaD is the most common cause of non-Alzheimer dementia in the aging population and often contributes to cognitive impairment in AD and other forms of so-called “mixed dementias” . Unlike AD, there are no pathological criteria for the diagnosis of VaD. The clinical criteria are poorly understood and validated. It’s a heterogeneous syndrome rather than a distinct disorder, in which the underlying cause is cerebrovascular disease in some form and its ultimate manifestation is dementia . Three common forms of ischemic lesions can result in VaD: 1) Large artery infarcts involving the cortex and subcortical regions due to thromboembolic occlusion of major intracranial arteries; 2) Small artery infarctions or lacunes attributed to arteriolosclerosis involving the penetrating arteries and affecting the thalamus, basal ganglia, internal capsule, brain stem and cerebellum; 3) Periventricular white matter disease resulting from chronic subcortical ischemia of small arteries affecting the neurons, oligodedrocytes and astrocytes. Multiple studies have shown that in nearly 6 to 32 % of cases with lobar and lacunar ischemic stroke, one can show post stroke cognitive impairment and dementia . The presence of microbleeds, a manifestation of small vessel disease, is also associated with cognitive decline. The number of infarcts and anatomic distribution of ischemic stroke, rather than the volume, determines the development of VaD. The more vulnerable areas are the hippocampus, angular gyrus, cingulate gyrus, frontal lobe or deep gray and white matter (thalamus, fornix, basal forebrain, caudate, globus pallidus, and the genu or anterior limb of the internal capsule) . Advanced age, increased severity of the stroke, recurrent strokes, white matter disease, cortical atrophy (particularly in the temporal lobe), hypertension, obesity, elevated homocysteine, hyperlipidemia, and diabetes mellitus are the common associated risk factors . The clinical presentation varies depending on cortical or subcortical ischemic lesions. Cortical lesions tend to be sudden onset with more focal neurodeficits, whereas subcortical lacunar infarcts and white matter disease have more gradual or stepwise decline of cognitive functions.
Chronic subdural hematoma (SDH)
Dementia with Lewy bodies (DLB)
Dementia with Lewy bodies (DLB) is considered as the second most common type of degenerative dementia after Alzheimer disease (AD). Cognitive dysfunction is the frequent initial presentation of DLB, with dementia eventually occurring in all cases. Unlike Alzheimer disease (AD), the patients with DLB often present with early impairments in attention, executive and visuospatial function, with memory affected later in the course of the disease . Other clinical manifestations are visual hallucinations, dysautonomia, parkinsonism, sleep disorders, and neuroleptic sensitivity. Radiologic features are not specific, but may be supportive in the diagnosis of DLB. Generalized brain atrophy may be noticed on MRI, similar to other neurodegenerative dementia. Few studies have shown atrophy of the putamen and dorsal mesopontine gray matter in DLB compared with AD on volumetric MRI scans . As per one study, there can be reduced fractional anisotropy in the parieto-occipital white matter tracts on diffusion tensor imaging in DLB, but not in AD . Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) scans may show decreased perfusion and metabolism in the occipital areas . The common differential diagnoses for DLB are Alzheimer disease (AD), Parkinson disease (PD), vascular dementia, other neurodegenerative dementias, and certain psychiatric disease. The diagnosis of DLB is primarily based on the clinical presentations, with radiologic features serving as helpful tool.
Dementia in Parkinson disease (PD)
Dementia is common and typically appears late in Parkinson disease (PD). Milder cognitive impairment represented by executive dysfunction and impaired visuospatial function is usually noted early in the disease . Other associated clinical features are visual hallucinations, bradykinesia, rigidity and resting tremor. There are no specific imaging features for Parkinson disease with dementia; however, one of the recent neuroimaging studies has described the high accuracy of diagnosing PD by demonstrating absence of normal hyperintensity in the nigrosome-1 of the dorsolateral substantia nigra (Swallow Tail sign) on Susceptibility Weighted Imaging (SWI) MR sequence . The most common differential diagnosis is Dementia with Lewy bodies (DLB). In PD, dementia generally occurs in the setting of well-established parkinsonism, whereas in DLB, dementia usually appears along with or before the development of parkinsonian signs. Quantitative morphometric MRI study can help in differentiating both entities with evidence of more pronounced cortical atrophy in DLB compared to PD.  Other differential diagnoses include progressive supranuclear palsy (PSP), corticobasal degeneration, Alzheimer disease and vascular dementia.
Multiple system atrophy- cerebellar type (MSA-C)
Progressive supranuclear palsy (PSP)
Frontotemporal lobar dementia (FTLD)
Huntington’s disease (HD)
Creutzfeldt-Jakob disease (CJD)
HIV-Associated dementia (HAD)
Sjogren’s syndrome (SS)
Multiple sclerosis (MS)
Delayed post hypoxic leukoencephalopathy (DPHL)
Acute methanol toxicity
Central pontine myelinolysis
Fragile X-associated tremor/Ataxia syndrome (FXTAS)
Intracranial dural AV fistula (dAVF)
Normal pressure hydrocephalus (NPH)
Non-Alzheimer’s dementia comprises several pathologies varying from rapid onset to gradually progressive disease spectrum. Often there is considerable clinical overlap, and neuroimaging features tend to be non-specific during the initial stage of disease. The rationale of conventional neuroimaging is not to offer definitive diagnoses, but to suggest possible differential diagnoses and track evolving changes on follow-up studies. Newer molecular imaging bio-markers combined with conventional neuroimaging techniques hold promise in assessing applications of novel disease-modifying drugs for treatment and response evaluation. An important aspect of neuroimaging is also to recognize reversible or treatable causes of dementia that can potentially be treated or halt further disease progression.
Information on grants
No grant or financial assistance were received from any source. The authors have no financial or intellectual conflict of interest.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9:63–75.e62Google Scholar
- Roman GC (2002) Vascular dementia may be the most common form of dementia in the elderly. J Neurol Sci 203–204:7–10View ArticlePubMedGoogle Scholar
- Hachinski V, Iadecola C, Petersen RC et al (2006) National institute of neurological disorders and stroke-Canadian stroke network vascular cognitive impairment harmonization standards. Stroke 37:2220–2241View ArticlePubMedGoogle Scholar
- Kalaria RN (2012) Cerebrovascular disease and mechanisms of cognitive impairment: evidence from clinicopathological studies in humans. Stroke 43:2526–2534View ArticlePubMedGoogle Scholar
- Benisty S, Gouw AA, Porcher R et al (2009) Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study. J Neurol Neurosurg Psychiatry 80:478–483View ArticlePubMedGoogle Scholar
- Srikanth VK, Quinn SJ, Donnan GA, Saling MM, Thrift AG (2006) Long-term cognitive transitions, rates of cognitive change, and predictors of incident dementia in a population-based first-ever stroke cohort. Stroke 37:2479–2483View ArticlePubMedGoogle Scholar
- Ballard CG, Burton EJ, Barber R et al (2004) NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia. Neurology 63:983–988View ArticlePubMedGoogle Scholar
- Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F (2007) Progression of leukoaraiosis and cognition. Stroke 38:2619–2625View ArticlePubMedGoogle Scholar
- Ragno M, Tournier-Lasserve E, Fiori MG et al (1995) An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Ann Neurol 38:231–236View ArticlePubMedGoogle Scholar
- Pantoni L, Pescini F, Nannucci S et al (2010) Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients. Neurology 74:57–63View ArticlePubMedGoogle Scholar
- Fujisawa H, Nomura S, Kajiwara K, Kato S, Fujii M, Suzuki M (2006) Various magnetic resonance imaging patterns of chronic subdural hematomas: indicators of the pathogenesis? Neurol Med Chir (Tokyo) 46:333–338, discussion 338–339 View ArticleGoogle Scholar
- Tiraboschi P, Salmon DP, Hansen LA, Hofstetter RC, Thal LJ, Corey-Bloom J (2006) What best differentiates Lewy body from Alzheimer’s disease in early-stage dementia? Brain 129:729–735View ArticlePubMedGoogle Scholar
- Kantarci K, Ferman TJ, Boeve BF et al (2012) Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies. Neurology 79:553–560PubMed CentralView ArticlePubMedGoogle Scholar
- Watson R, Blamire AM, Colloby SJ et al (2012) Characterizing dementia with Lewy bodies by means of diffusion tensor imaging. Neurology 79:906–914PubMed CentralView ArticlePubMedGoogle Scholar
- Mirzaei S, Rodrigues M, Koehn H, Knoll P, Bruecke T (2003) Metabolic impairment of brain metabolism in patients with Lewy body dementia. Eur J Neurol 10:573–575View ArticlePubMedGoogle Scholar
- Svenningsson P, Westman E, Ballard C, Aarsland D (2012) Cognitive impairment in patients with Parkinson’s disease: diagnosis, biomarkers, and treatment. Lancet Neurol 11:697–707View ArticlePubMedGoogle Scholar
- Schwarz ST, Afzal M, Morgan PS, Bajaj N, Gowland PA, Auer DP (2014) The ‘swallow tail’ appearance of the healthy nigrosome - a new accurate test of Parkinson’s disease: a case-control and retrospective cross-sectional MRI study at 3T. PLoS ONE 9:e93814PubMed CentralView ArticlePubMedGoogle Scholar
- Beyer MK, Larsen JP, Aarsland D (2007) Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies. Neurology 69:747–754View ArticlePubMedGoogle Scholar
- Kawai Y, Suenaga M, Takeda A et al (2008) Cognitive impairments in multiple system atrophy: MSA-C vs MSA-P. Neurology 70:1390–1396View ArticlePubMedGoogle Scholar
- Seppi K, Poewe W (2010) Brain magnetic resonance imaging techniques in the diagnosis of parkinsonian syndromes. Neuroimaging Clin N Am 20:29–55View ArticlePubMedGoogle Scholar
- McGinnis SM (2012) Neuroimaging in neurodegenerative dementias. Semin Neurol 32:347–360PubMedGoogle Scholar
- Righini A, Antonini A, De Notaris R et al (2004) MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease. AJNR Am J Neuroradiol 25:927–932PubMedGoogle Scholar
- Adachi M, Kawanami T, Ohshima H, Sugai Y, Hosoya T (2004) Morning glory sign: a particular MR finding in progressive supranuclear palsy. Magn Reson Med Sci 3:125–132View ArticlePubMedGoogle Scholar
- Hussl A, Mahlknecht P, Scherfler C et al (2010) Diagnostic accuracy of the magnetic resonance Parkinsonism index and the midbrain-to-pontine area ratio to differentiate progressive supranuclear palsy from Parkinson’s disease and the Parkinson variant of multiple system atrophy. Mov Disord 25:2444–2449View ArticlePubMedGoogle Scholar
- Warmuth-Metz M, Naumann M, Csoti I, Solymosi L (2001) Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol 58:1076–1079View ArticlePubMedGoogle Scholar
- Quattrone A, Nicoletti G, Messina D et al (2008) MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology 246:214–221View ArticlePubMedGoogle Scholar
- Viskontas IV, Possin KL, Miller BL (2007) Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior. Ann N Y Acad Sci 1121:528–545View ArticlePubMedGoogle Scholar
- Hodges JR, Patterson K, Ward R et al (1999) The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer’s disease: a comparative neuropsychological study. Neuropsychology 13:31–40View ArticlePubMedGoogle Scholar
- Eslinger PJ, Dennis K, Moore P, Antani S, Hauck R, Grossman M (2005) Metacognitive deficits in frontotemporal dementia. J Neurol Neurosurg Psychiatry 76:1630–1635PubMed CentralView ArticlePubMedGoogle Scholar
- Rankin KP, Gorno-Tempini ML, Allison SC et al (2006) Structural anatomy of empathy in neurodegenerative disease. Brain 129:2945–2956PubMed CentralView ArticlePubMedGoogle Scholar
- Gorno-Tempini ML, Dronkers NF, Rankin KP et al (2004) Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 55:335–346PubMed CentralView ArticlePubMedGoogle Scholar
- Walker FO (2007) Huntington’s disease. Lancet 369:218–228View ArticlePubMedGoogle Scholar
- Bamford KA, Caine ED, Kido DK, Cox C, Shoulson I (1995) A prospective evaluation of cognitive decline in early Huntington’s disease: functional and radiographic correlates. Neurology 45:1867–1873View ArticlePubMedGoogle Scholar
- Young AB, Penney JB, Starosta-Rubinstein S et al (1986) PET scan investigations of Huntington’s disease: cerebral metabolic correlates of neurological features and functional decline. Ann Neurol 20:296–303View ArticlePubMedGoogle Scholar
- Smart JM, Wood A (2001) Value of fluid-attenuated inversion recovery MR imaging in an unusual case of sporadic Creutzfeldt-Jakob disease. AJR Am J Roentgenol 177:948–949View ArticlePubMedGoogle Scholar
- Lee H, Hoffman C, Kingsley PB, Degnan A, Cohen O, Prohovnik I (2010) Enhanced detection of diffusion reductions in Creutzfeldt-Jakob disease at a higher B factor. AJNR Am J Neuroradiol 31:49–54View ArticlePubMedGoogle Scholar
- Vitali P, Maccagnano E, Caverzasi E et al (2011) Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 76:1711–1719PubMed CentralView ArticlePubMedGoogle Scholar
- Thurnher MM, Thurnher SA, Fleischmann D et al (1997) Comparison of T2-weighted and fluid-attenuated inversion-recovery fast spin-echo MR sequences in intracerebral AIDS-associated disease. AJNR Am J Neuroradiol 18:1601–1609PubMedGoogle Scholar
- Tucker KA, Robertson KR, Lin W et al (2004) Neuroimaging in human immunodeficiency virus infection. J Neuroimmunol 157:153–162View ArticlePubMedGoogle Scholar
- Alexander EL, Beall SS, Gordon B et al (1988) Magnetic resonance imaging of cerebral lesions in patients with the Sjogren syndrome. Ann Intern Med 108:815–823View ArticlePubMedGoogle Scholar
- Yoshikawa K, Hatate J, Toratani N et al (2012) Prevalence of Sjogren’s syndrome with dementia in a memory clinic. J Neurol Sci 322:217–221View ArticlePubMedGoogle Scholar
- Anderson VM, Fox NC, Miller DH (2006) Magnetic resonance imaging measures of brain atrophy in multiple sclerosis. J Magn Reson Imaging 23:605–618View ArticlePubMedGoogle Scholar
- Shprecher D, Mehta L (2010) The syndrome of delayed post-hypoxic leukoencephalopathy. NeuroRehabilitation 26:65–72PubMed CentralPubMedGoogle Scholar
- Shprecher DR, Flanigan KM, Smith AG, Smith SM, Schenkenberg T, Steffens J (2008) Clinical and diagnostic features of delayed hypoxic leukoencephalopathy. J Neuropsychiatry Clin Neurosci 20:473–477View ArticlePubMedGoogle Scholar
- Jammalamadaka D, Raissi S (2010) Ethylene glycol, methanol and isopropyl alcohol intoxication. Am J Med Sci 339:276–281View ArticlePubMedGoogle Scholar
- Blanco M, Casado R, Vazquez F, Pumar JM (2006) CT and MR imaging findings in methanol intoxication. AJNR Am J Neuroradiol 27:452–454PubMedGoogle Scholar
- Ghika-Schmid F, Ghika J, Assal G, Bogousslavsky J (1999) Callosal dementia: behavioral disorders related to central and extrapontine myelinolysis. Rev Neurol (Paris) 155:367–373Google Scholar
- Ruzek KA, Campeau NG, Miller GM (2004) Early diagnosis of central pontine myelinolysis with diffusion-weighted imaging. AJNR Am J Neuroradiol 25:210–213PubMedGoogle Scholar
- Brunberg JA, Jacquemont S, Hagerman RJ et al (2002) Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction. AJNR Am J Neuroradiol 23:1757–1766PubMedGoogle Scholar
- Netravathi M, Pal PK, Bharath RD, Ravishankar S (2011) Intracranial dural arteriovenous fistula presenting as parkinsonism and cognitive dysfunction. J Clin Neurosci 18:138–140View ArticlePubMedGoogle Scholar
- Hurst RW, Bagley LJ, Galetta S et al (1998) Dementia resulting from dural arteriovenous fistulas: the pathologic findings of venous hypertensive encephalopathy. AJNR Am J Neuroradiol 19:1267–1273PubMedGoogle Scholar
- Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH (1965) Symptomatic occult hydrocephalus with “normal” cerebrospinal-fluid pressure. A treatable syndrome. N Engl J Med 273:117–126View ArticlePubMedGoogle Scholar
- Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM (2005) Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 57:S4-16; discussion ii-vGoogle Scholar
- Lee PW, Hung BK, Woo EK, Tai PT, Choi DT (1989) Effects of radiation therapy on neuropsychological functioning in patients with nasopharyngeal carcinoma. J Neurol Neurosurg Psychiatry 52:488–492PubMed CentralView ArticlePubMedGoogle Scholar
- Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384View ArticlePubMedGoogle Scholar
- Sahadevan S, Pang WS, Tan NJ, Choo GK, Tan CY (1997) Neuroimaging guidelines in cognitive impairment: lessons from 3 cases of meningiomas presenting as isolated dementia. Singap Med J 38:339–343Google Scholar