Classifying late-onset dementia with MRI: Is arteriosclerotic brain degeneration the most common cause of Alzheimer’s syndrome?

Figures & data

Figure 1 Mesiotemporal atrophy in the AD MR class of converters to dementia of the Alzheimer type. These oblique coronal reformatted T1-weighted images at the level of the anterior parahippocampal gyri are from a nonconverter (A) and three AD MR type converters (B, C and D), respectively 41 (B), 17 (C) and 11 (D) months before diagnosis of dementia. Compared with the nonconverter, these converters showed predominantly left mesial temporal atrophy and ventricular enlargement and marked atrophy of the AD type; there was a marked dilatation of the left rhinal sulcus (long arrows) and concave superior border of the anterior amygdala region (short arrows).

Table 1 Classification of MR profiles

Baseline MR category	Baseline MR criteria predicting conversion
Possible AD (n = 34)	Advanced AD subtype (n = 3)
Entorhinal cortex value within the two lowest quartiles at least on the left side	Left and right entorhinal values within the lowest quartile without any significant subcortical nor periventricular white matter changes* + blood stroke within the two lowest quartiles
	Other predementia MR profiles (n = 8)
Possible cerebrovascular dysfunction
Low arterial windkessel effect (n = 18)	Microangiopathy subtype (n = 6)
IP and blood stroke values Within the two highest quartiles	Subcortical and periventricular white matter changes* + TCBF outside the highest quartile
	Marked cortical thinning subtype (n = 1)
	Left and right entorhinal values within the lowest quartile + superficial venous outflow within the two lowest quartiles
Windkessel dysfunction not related to the large arteries (n = 14)	Venous subtype (n = 1)
Blood stroke value within the two highest quartiles IP outside the two highest quartiles	Subcortical and periventricular white matter changes* + deep venous flow within the two lowest quartiles despite TCBF within the two highest quartiles
Low cortical perfusion (n = 23)	Very low craniospinal compliance subtype (n = 3)
Arterial and superficial venous flow rates within the two lowest quartiles	TCBF within the lowest quartile + compliance ratio within the lowest quartile
	Nonspecific severe brain atrophy subtype (n = 3)
	TCBF within the lowest quartile + marked widening of the sulci or +superficial and deep venous outflow, blood and CSF strokes within the lowest quartile
	Other predementia MR profiles (n = 3)

Notes: The term “subcortical white matter changes” indicates larger perivascular deep white matter changes; the term “periventricular white matter changes” indicates larger subependymal changes or marked splenial changes. The term “other predementia MR profiles” refers to one or more of the previously defined predementia MR profiles; advanced AD subtype, microangiopathy subtype, marked cortical thinning subtype, venous subtype, very low craniospinal compliance subtype, or nonspecific severe brain atrophy subtype.

Abbreviations: IP, index of arterial pulsatility; TCBF, total supratentorial cerebral blood flow; CSF, cerebrospinal fluid.

Table 2 Demographic and clinical baseline characteristics according to final clinical diagnosis

Baseline variables	Nonconverters (n = 45)	Converters (n = 17)
Age	71 ± 6	75 ± 4
Females/males	10/7	28/17
Years of schooling	12 ± 4	11 ± 4
Cardiovascular risk score	1 ± 1	1 ± 1
MMSE (total score)	28 ± 1	27 ± 1
Grober and Buschke test, DTR score	15 ± 1	11 ± 5
Trail making test, substraction score	82 ± 65	129 ± 91
Mobility scores	1.6 ± 1.6*	3.1 ± 2*

* Notes: Mobility scores are only reported in patients without known cause of mobility dysfunction (15 converters and 40 nonconverters).

Abbreviations: MMSE, MiniMental State Examination; DTR, delayed total recall score.

Table 3 Demographic and clinical baseline characteristics according to baseline MR subtypes (non-AD or AD type, responding or not to MR criteria of conversion)

Baseline clinical variables	Baseline MR profiles*
	Possible AD (non-converters)	AD predementia (converters)	Possible cerebrovascular dysfunction (non-converters)	Non-AD predementia (converters)
Age	73 ± 7	78 ± 2	68 ± 5	75 ± 5
Females/males	2/2	0/3	11/3	3/3
Years of schooling	16 ± 3	10 ± 6	13 ± 4	13 ± 5
Cardiovascular risk score	1 ± 1	2 ± 1	1 ± 1	1 ± 1
MMSE total score	27 ± 1	27 ± 1	28 ± 1	28 ± 1
Grober-Buschke test, DTR score	14 ± 1	12 ± 5	16 ± 1	14 ± 3
Trail Making Test, substraction score	97 ± 45	36 ± 6	64 ± 35	130 ± 92
Mobility scores**	0 ± 1	1 ± 0	2 ± 2	4 ± 2

* Notes: Patients with “mixed” MR presentations characterized by coexistence of MR profiles of at least possible AD and possible cerebrovascular are not included in these subgroups;

** mobility scores are presented only in patients with no known cause of mobility (2 of the 4 patients with pure possible AD MR profile, all the 3 patients with pure AD predementia MR profiles, all the 14 patients with MR profile of possible pure cerebrovascular dysfunction, and all the 6 patients with pure predementia non-AD profiles).

Abbreviations: MMSE, MiniMental State Examination; DTR, delayed total recall score.

Table 4 Baseline MR characteristics of study sample

Baseline variables	Range (25th percentile/median/75th percentile)
Left entorhinal measurements (mm^2)	209 to 692 (394/438/502)
Right entorhinal measurements (mm^2)	299 to 585 (395/437/502)
Index of entorhinal asymmetry	−16 to 26 (−4.72/0.85/4.61)
Total cerebral blood flow (TCBF, mL/min)	511 to 1219 (654/752/844)
Deep venous outflow (mL/min)	64 to 188 (93/119/139)
Superficial venous outflow (mL/min)	121 to 426 (240/281/322)
Index of arterial pulsatility (IP)	0.78 to 1.67(0,99/1,08 / 1, 25)
Blood stroke per min (mL)	48 to 179 (74/90/106)
Cerebrospinal fluid stroke per min (mL)	0.67 to 10,37 (3.2/4.20/5.9)
Relative craniospinal compliance	5 to 131 (15/20/29)

Table 5 Distribution of MR profiles according to final clinical diagnosis

MR changes	N	Predementia MR profiles	MR classification	Final clinical diagnosis
Isolated possible AD (A)	4	absent	not pre-dementia	not demented
	3	advanced AD	advanced AD	DAT
Isolated low arterial windkessel effect (B)	3	absent	not predementia	not demented
	2	microangiopathy	VD/severe arterioscl. brain degeneration	DAT
Isolated low nonarterial windkessel effect (C)	5	absent	not predementia	not demented
Isolated low cortical perfusion (D)	4	absent	not predementia	not demented
	1	nonspecific severe brain atrophy	nonspecific severe brain atrophy	DAT
	1	very low craniosp. compliance	VD/ severely restricted brain perf.	DAT
	2	very low craniosp. compliance	VD/severely restricted brain perf.	VaD
(A) + (B)	5	absent	not predementia	not demented
	1	microangiopathy	VD/severe arterioscl. brain degeneration	DAT
	1	marked cortical thinning	VD/severe arterioscl. brain degeneration	DAT
(A) + (C)	7	absent	not pre-dementia	not demented
	1	venous subtype	VD/venous cognitive impairment	DAT
(A) + (D)	5	absent	not pre-dementia	not demented
	2	nonspecific severe brain atrophy	nonspecific severe brain atrophy	DAT
(B) + (D)	1	absent	not predementia	not demented
(C) + (D)	1	absent	not predementia	not demented
(A) + (B) + (D)	2	absent	not predementia	not demented
	3	microangiopathy	VD/severe arterioscl. brain degeneration	DAT
Absence of (A), (B), (C) or (D)	8	absent	not pre-dementia	not demented

Abbreviations: AD, Alzheimer’s disease; VD, cerebrovascular disease; DAT, dementia of the Alzheimer type; VaD, vascular dementia; craniospin, craniospinal; arterioscl, arteriosclerotic; perf., perfusion.

Figure 2 Mesiotemporal atrophy in the vascular MR class of converters to dementia of the Alzheimer type. These oblique coronal reformatted T1-weighted images at the level of the anterior parahippocampal gyri are from five vascular type converters; one with arterial windkessel dysfunction and cerebral microangiopathy 9 months before diagnosis of dementia (A), one with arterial windkessel dysfunction and marked cortical atrophy 33 months before diagnosis of dementia (B), one with venous windkessel dysfunction 12 months before the diagnosis of dementia (C), one with resistive MR subtype 24 months before diagnosis of dementia (D), and the last one with a MR pattern of global cerebral hypoperfusion 13 months before diagnosis of dementia (E). There is no disproportionate enlargement of the left rhinal sulcus (long arrows), no marked concavity of the upper limit of the left amygdala region (short arrows), nor marked evidence of left predominance of brain atrophy.